Noted This Week - Archive 2020

• The FDA approved the RET kinase inhibitor pralsetinib (Gavreto; Blueprint Medicines/Genentech) in patients with metastatic RET fusion–positive non–small cell lung cancer. The approval was based on the phase I/II ARROW trial in which newly diagnosed patients had an overall response rate (ORR) of 70% and patients previously treated with chemotherapy had an ORR of 57%. The FDA is also assessing pralsetinib in RET-mutant medullary thyroid cancer and RET fusion–positive thyroid cancer.
• The agency also issued an alert that atezolizumab (Tecentriq; Roche) plus paclitaxel may not be effective in patients with newly diagnosed, inoperable, locally advanced or metastatic triple-negative breast cancer. In the phase III IMpassion131 trial, the combination did not significantly reduce the risk of cancer progression and death compared with a placebo plus paclitaxel in patients with PD-L1–positive disease. Atezolizumab plus paclitaxel is not approved for this indication, but atezolizumab plus paclitaxel protein-bound (Abraxane; Celgene) is approved and will continue to be assessed by the agency.
• AbbVie announced that it will pay China’s I-Mab $180 million up front in a deal that could be worth up to $1.74 billion in milestone payments. The deal centers on I-Mab’s investigational anti-CD47 agent lemzoparlimab, currently in phase I testing for multiple cancers. The companies will collaborate on future clinical trials, and should they succeed, AbbVie will gain exclusive rights to license the drug outside of China.
• A paper in The New England Journal of Medicine reported that the androgen-receptor inhibitor darolutamide (ODM-201; Bayer/Orion) may significantly improve overall survival in nonmetastatic, castration-resistant prostate cancer compared with a placebo. In the phase III ARAMIS trial, 83% of patients who received the therapy were still alive at 3 years, compared with 77% of patients who received a placebo, and the therapy reduced the risk of death by 31%.

• The Leukemia & Lymphoma Society launched the Beat COVID trial in patients with blood cancer and COVID-19. Initially, the trial will test the Bruton tyrosine kinase inhibitor acalabrutinib (Calquence; AstraZeneca) in patients with various types of blood cancer who test positive for the virus. Beat COVID is based on the framework for the organization’s Beat AML Master Trial, a precision medicine umbrella trial for acute myeloid leukemia.
• Infrequent smokers may still have a high risk of lung cancer mortality, according to findings presented at the European Respiratory Society International Congress. Researchers analyzed data from 18,730 people classified as never-smokers, former smokers, and current smokers. They found that current smokers who smoke fewer than 10 cigarettes per day were 2.5 times more likely to die from respiratory disease and almost 9 times more likely to die from lung cancer than never-smokers.

• The FDA approved azacitidine tablets (Onureg; Celgene) in patients with acute myeloid leukemia who have achieved remission after initial chemotherapy but aren’t eligible for curative therapy. The approval was based on the phase III QUAZAR AML-001 trial, in which patients who received the drug had a median overall survival of 24.7 months, compared with 14.8 months in patients who received a placebo. The tablets are an oral form of the DNA-hypomethylating agent azacitidine, which is administered by injection.
• Afatinib (Gilotrif; Boehringer Ingelheim) followed by osimertinib (Tagrisso; AstraZeneca) may be a promising treatment sequence in patients with EGFR-positive non–small cell lung cancer who acquire T790M mutations. In a final analysis of the retrospective GioTag study, patients who received the sequence had a median overall survival of 37.6 months and a median time to treatment failure of 27.7 months. Afatinib is a second-generation tyrosine kinase inhibitor (TKI) that binds irreversibly to EGFR, HER2, and HER4; osimertinib is a third-generation irreversible EGFR TKI.

• More men with high-risk prostate cancer are undergoing prostatectomies, researchers reported in JAMA Network Open. Between 2004 and 2016, the proportional rate of men diagnosed with high-risk prostate cancer increased from 11.8% to 20.4%, whereas the rate of men who had prostatectomies increased from 22.8% to 40.5%; the rate of radiotherapy decreased from 59.7% to 43.3%.
• The NCI renewed the comprehensive cancer designation of the Herbert Irving Comprehensive Cancer Center at Columbia University Irving Medical Center and New York-Presbyterian in New York, NY. The agency also awarded the center $26.5 million in funding over five years. Since 2015, the number of patients enrolled in trials at Herbert Irving has increased by 40%; almost 50% of trial participants are underrepresented minorities.

• The NCI and Cancer Research UK launched a Cancer Grand Challenges partnership to support multidisciplinary cancer research. Together, the institutions will select four research teams, each of which will receive approximately $25 million in funding over 5 years. The partnership builds on Cancer Research UK’s existing Grand Challenge initiative, which has awarded two rounds of funding since 2015; the NCI will contribute funding from its Provocative Questions initiative.
• The European Society of Medical Oncology published recommendations on next-generation sequencing (NGS) in patients with metastatic cancers. The guidelines recommend NGS in patients with non–small cell lung cancer (NSCLC), prostate cancer, ovarian cancer, and cholangiocarcinoma, and tumor mutational burden testing in patients with neuroendocrine tumors as well as cervical, salivary, thyroid, and vulvar cancers. The document also encourages academic research centers to perform NGS.
• The FDA approved the FoundationOne Liquid CDx liquid biopsy test for genomic sequencing in patients with solid tumors. The test also received specific companion diagnostic approvals for the PARP inhibitor rucaparib (Rubraca; Clovis Oncology) in prostate cancer and the EGFR inhibitors gefitinib (Iressa; AstraZeneca), osimertinib (Tagrisso; AstraZeneca), and erlotinib (Tarceva; Genentech) in NSCLC. The approval was based on data from more than 7,500 samples and 30,000 variants across 30-plus cancers.

• The agency also released a draft guidance on evaluating cancer drugs in patients with brain metastases. The document provides recommendations about designing trials to test cancer agents in these patients, including how to decide which patients to include, how to factor in prior therapies, and how to assess brain metastases. The guidance is available for comment until October 26.
• Patients with blood cancers may develop more severe COVID-19 symptoms, according to findings in The Lancet Oncology. Researchers analyzed data from 1,044 patients with cancer and COVID-19 enrolled in the UK Coronavirus Cancer Monitoring Project. They found that those with leukemia, lymphoma, or myeloma were more likely to develop serious COVID-19 infections than those with solid tumors.
• Novartis announced that asciminib (ABL001) may be effective in patients with Philadelphia chromosome–positive chronic myeloid leukemia who have received prior tyrosine kinase inhibitors (TKI). In the ASCEMBL trial, the agent achieved a superior molecular response compared with the TKI bosutinib (Bosulif; Pfizer). Asciminib is a STAMP inhibitor that targets the ABL myristoyl pocket.

• Bristol-Myers Squibb (BMS) announced it will pay Dragonfly Therapeutics $475 million up front to acquire Dragonfly's IL12 investigational immunotherapy program. In the deal, BMS will take over development and commercialization of the extended half-life cytokine DF6002, which is being tested in patients with advanced solid tumors in a phase I/II trial.
• Turning Point Therapeutics reported that the investigational tyrosine kinase inhibitor (TKI) repotrectinib may be effective in certain patients with ROS1-positive non–small cell lung cancer (NSCLC) and NTRK-positive solid tumors. In the phase II TRIDENT-1 trial, the drug elicited responses in six of seven patients with ROS1-positive, TKI-naïve NSCLC, and in multiple cohorts of patients with ROS1-positive NSCLC who had received a prior TKI. Additionally, three of six patients with NTRK-positive solid tumors previously treated with a TKI responded to the agent.
• Almost half of patients with breast cancer experienced delays in treatment during the early weeks of the COVID-19 pandemic, according to study findings. Researchers analyzed online questionnaire data from 609 patients with breast cancer gathered from April 2–27, 2020. Overall, 44% of patients reported delays in care, of which 79% were for routine follow-up appointments, 66% were for breast reconstruction, and 60% were for diagnostic imaging. Around 30% of patients reported delays in radiation, infusion therapies, or surgical tumor removal.

• The FDA placed a full clinical hold on a phase I trial testing the CAR-T therapy P-PSMA-101 (Poseida Therapeutics) in metastatic castration-resistant prostate cancer after a patient died of liver failure. The company is still investigating the death, but the patient’s symptoms were consistent with macrophage activation syndrome. The company will submit a plan to the FDA requesting permission to restart the trial, after which the agency will have 30 days to respond.
• The FDA approved daratumumab (Darzalex; Janssen) plus carfilzomib (Kyprolis; Amgen) and dexamethasone to treat patients with relapsed/refractory multiple myeloma who have received one to three prior therapies. The approval was based in part on positive results in the phase III CANDOR trial, in which the triplet reduced the risk of disease progression or death by 37% compared with carfilzomib and dexamethasone alone.
• The FDA Oncologic Drugs Advisory Committee voted 9 to 1 in favor of remestemcel-L (Ryoncil; Mesoblast Limited) to treat pediatric patients with steroid-refractory acute graft-versus-host disease. The approval recommendation was based on a single-arm study and two randomized phase III trials in which the drug elicited objective response rates greater than 65%. The FDA doesn’t need to follow the committee’s recommendation, although it usually does so.

• Siemens Healthineers announced it will buy Varian Medical Systems for $16.4 billion in an effort to expand its oncology profile. Varian specializes in radiation therapy, producing hardware such as linear accelerators, radiosurgery devices, and proton therapy systems, as well as software centered on cancer care and analytics.
• The FDA approved the Guardant360 CDx liquid biopsy test for genomic sequencing in patients with any solid tumor. The agency also approved the test as a companion diagnostic for patients with non–small cell lung cancer (NSCLC) who may benefit from treatment with osimertinib (Tagrisso; AstraZeneca) based on the presence of EGFR mutations. The approvals were based on data from 5,000 samples, as well as a retrospective analysis of the phase III FLAURA and AURA3 trials.
• The agency also approved tafasitamab-cxix (Monjuvi; MorphoSys) plus lenalidomide in certain patients with relapsed/refractory diffuse large B-cell lymphoma. The approval was based on the phase II L-MIND trial in which the combination elicited an overall response rate of 55% and a median duration of response of 21.7 months. The approval is the first for tafasitamab-cxix, a CD19-directed cytolytic antibody.
• New cancer diagnoses declined significantly at the beginning of the COVID-19 pandemic, according to findings in JAMA Network Open. Researchers found that for combined breast, colorectal, lung, pancreatic, gastric, and esophageal cancers, weekly diagnoses dropped by 46.4% during the first two months of the pandemic; decreases ranged from 24.7% for pancreatic cancer to 51.8% for breast cancer.

• Dana-Farber Cancer Institute in Boston, MA, launched the Center for BRCA and Related Genes. The center will specialize in treatment for, prevention of, and research into BRCA-related malignancies—including gynecologic, prostate, pancreatic, and breast cancers. Patients treated at the center will have access to cutting-edge therapies, including clinical trials of novel agents; a key area of research will be early detection of ovarian and pancreatic cancers.
• The ALK inhibitor ensartinib (Xcovery) may be effective in patients with advanced NSCLC and ALK alterations who have not received a previous ALK inhibitor, researchers reported at the World Conference on Lung Cancer 2020 Virtual Presidential Symposium. In the phase III eXalkt3 trial, patients treated with the drug had a median progression-free survival of 25.8 months, compared with 12.7 months in patients who received crizotinib (Xalkori; Pfizer).
• A paper in The New England Journal of Medicine revealed that NSCLC mortality has decreased in recent years. Between 2013 and 2016, NSCLC mortality among men dropped by 6.3%, whereas incidence from 2008 to 2016 declined by 3.1%—suggesting the decrease in mortality cannot be completely attributed to lower incidence. Two-year survival in men diagnosed in 2014 was 35%, compared with 26% in men diagnosed in 2001; similar patterns were seen in women.
• The FDA released a final guidance on drug development for male breast cancer. The document recommends including men in breast cancer trials unless there is a scientific reason to exclude them. It also it offers suggestions for assessing agents in men when they were not included in trials, such as extrapolating based on preclinical research into a drug’s mechanism of action, or utilizing small single-arm trials or real-world data.

• AstraZeneca will pay Daiichi Sankyo $1 billion up front and up to $5 billion more in milestone payments in a deal that focuses on Daiichi Sankyo’s investigational agent DS-1062. The companies will jointly develop and commercialize DS-1062, a TROP2-directed antibody–drug conjugate (ADC) being tested in non–small cell lung cancer (NSCLC) and triple-negative breast cancer. The companies made a similar deal in March 2019 centered on Daiichi Sankyo’s HER2-targeted ADC, trastuzumab deruxtecan (Enhertu).
• The FDA approved brexucabtagene autoleucel (Tecartus; Gilead) for patients with relapsed/refractory mantle cell lymphoma. The approval was based on the phase II ZUMA-2 trial in which 60 patients had an objective response rate (ORR) of 87% and a complete remission rate of 62%. Brexucabtagene autoleucel is a CD19-directed chimeric antigen receptor T-cell therapy.
• The agency also granted an orphan drug designation to zenocutuzumab (Zeno; Merus) for patients with previously treated pancreatic cancer who have NRG1 mutations. The agent is a bispecific antibody that binds to HER2 and HER3; it is thought to block the interaction between HER3 and its ligand NRG1. Zenocutuzumab is under evaluation in the phase I/II eNRGy trial of NRG1-positive solid cancers.
• Spectrum Pharmaceuticals announced that the EGFR inhibitor poziotinib may be effective in patients with previously treated NSCLC who have HER2 exon 20 insertion mutations. In the phase II ZENITH20 trial, 90 patients had an ORR of 27.8%, a disease control rate of 70%, and median progression-free survival of 5.5 months.

• The IL6 inhibitor tocilizumab (Actemra; Roche) may not improve outcomes in patients with severe COVID-19 infections. In the phase III COVACTA trial, the agent did not meet its primary endpoint—improved health of patients hospitalized with severe COVID-19–associated pneumonia—or its secondary endpoint—reduced mortality after 4 weeks. In April, Sanofi/Regeneron reported similarly disappointing results in a randomized trial of the IL6 inhibitor sarilumab (Kevzara); IL6 inhibitors are also being investigated in various solid and blood cancers.
• The American Cancer Society (ACS) released guidelines recommending cervical cancer screening with primary human papillomavirus (HPV) testing every 5 years starting at age 25. The new recommendation is based on evidence suggesting that fewer women in their early 20s are developing precancerous cervical lesions due to higher HPV vaccination rates, and cases of cervical cancer are rare between ages 20 and 24. Previously, the ACS recommended a Pap test every 3 years starting at age 21, transitioning to a Pap test plus HPV testing every 5 years at age 30.

• In his keynote address opening the American Association for Cancer Research (AACR) Virtual Meeting: COVID-19 and Cancer, held July 20–22, National Institute of Allergy and Infectious Diseases Director Anthony Fauci, MD, said that disruptions in cancer screening, treatment, and research may have a significant long-term impact, citing a recent editorial that estimated 10,000 additional deaths over the next decade from breast and colorectal cancers alone. He also cautioned that the world will have pandemics in the future. "Just as emerging infections provide for us a perpetual challenge, we need to be perpetually prepared."
• Numerous speakers at the AACR COVID-19 conference praised the speed with which researchers have advanced potential treatments—as well as their willingness to work collaboratively and share data. However, Solange Peters, MD, PhD, of Centre Hospitalier Universitaire Vaudois in Lausanne, Switzerland, also reminded attendees about "humbling lessons from the crisis," such as errors in published papers that lacked peer review or that were reviewed by researchers without the appropriate expertise.
• Researchers have found considerable overlap between cellular pathways for cancer and COVID-19. During a session at the AACR meeting, cancer scientists discussed their work on such pathways, including research on CD8 T-cell responses to the virus and on inhibitors of the IL6 and Bruton tyrosine kinase pathways. "Cancer scientists have spent decades interrogating these pathways—mapping them in a super high molecular resolution and using them to develop targeted therapies," said moderator Dafna Bar-Sagi, PhD, of NYU Langone Health in New York, NY. Thus, these scientists have "the unique opportunity to make meaningful contributions in real time to understanding and treating COVID-19."
• During a forum on COVID-19 and clinical trials, panelists discussed changes to trials necessitated by the pandemic that could be beneficial moving forward—such as moving aspects of care to local sites, providing patients with at-home monitoring tools, and embracing telemedicine. "We have a lot of the tools—it’s, I think … a mindset in utilizing those tools," said Patricia LoRusso, DO, of Yale University School of Medicine in New Haven, CT. "We may be surprised at not only how much faster we may be able to recruit the trials—how many more patients—but the diversity of patients that we may be able to bring on board."

• In a study of 2,186 patients in the United States with both cancer and COVID-19, those who were treated with hydroxychloroquine plus other drugs were more than twice as likely to die as those who didn’t receive hydroxychloroquine. Additionally, Black patients were half as likely to receive remdesivir—which was associated with reduced mortality—as white patients, and high-dose corticosteroids were linked to increased mortality, although this difference was not significant.
• Gilead will pay $300 million for a 49.9% stake in Tizona Therapeutics, with an option to acquire the remainder of the company for up to an additional $1.25 billion. In the deal, Gilead will gain access to Tizona’s investigational HLA-G inhibitor, TTX-080, which is being tested in a phase Ib trial of advanced solid tumors.
• Incyte announced that the JAK 1/2 inhibitor ruxolitinib (Jakafi) may lead to better outcomes in patients with acute GVHD who do not respond to steroids. In the phase III REACH3 trial, the agent improved overall response rate, failure-free survival, and patient-reported symptoms compared with standard treatment. The FDA approved ruxolitinib for this indication based on results of the phase II REACH1 trial.
• The NCI awarded more than $29 million to the Huntsman Cancer Institute at the University of Utah in Salt Lake City and renewed the center’s designation as a comprehensive cancer center for the next 7 years. The grant will support the continued expansion of Huntsman, which has recruited more than 70 cancer researchers over the past 5 years and more than doubled the number of patients participating in clinical trials. The center is one of 50 NCI-designated comprehensive cancer centers.

• Roche made a $775 million deal with Blueprint Medicines that could be worth up to $927 million more in milestone payments. The deal centers on Blueprint’s RET inhibitor, pralsetinib (BLU-667), which is under FDA review for RET fusion–positive non–small cell lung cancer, RET-mutant medullary thyroid cancer, and RET fusion–positive thyroid cancer. Earlier this year, the FDA approved Lilly’s RET inhibitor selpercatinib (Retevmo) for the same indications.
• The FDA Oncologic Drugs Advisory Committee voted 12 to 0 in favor of belantamab mafodotin (GSK2857916; GlaxoSmithKline), which targets B-cell maturation antigen, for patients with relapsed/refractory multiple myeloma who have received at least four prior therapies. The approval recommendation was based on the DREAMM-2 trial, in which the drug elicited a response in 34% of patients—and came despite previous concerns that the agent is associated with keratopathy, an eye-related side effect that can lead to severe vision loss. The FDA doesn’t need to follow the committee’s recommendation, although it usually does so.
• The FDA released four final guidances aimed at increasing and broadening participation in cancer clinical trials. Three of the guidances focus on expanding eligibility for subsets of patients, including those with HIV or hepatitis B or C virus infections, brain metastases, and organ dysfunction or prior or concurrent malignancies. The additional guidance outlines considerations for including pediatric patients in oncology trials.

• The U.S. Court of Appeals for the Federal Circuit upheld a previous ruling by the U.S. District Court in Boston, MA, that two U.S. scientists should be listed as inventors on six cancer immunotherapy patents. Gordon Freeman, PhD, of Dana-Farber Cancer Institute in Boston and Clive Wood, PhD, of Boehringer Ingelheim will be added to the patents, which were previously issued to Ono Pharmaceutical and Tasuku Honjo, MD, PhD, of Kyoto University in Japan. The patents describe the PD-1 pathway, which was foundational to the development of the PD-1 inhibitor nivolumab (Opdivo; Bristol-Myers Squibb).
• A survey of 157 cancer organizations in 56 countries revealed the impact of COVID-19 on patients. On the survey, 67% of organizations said cancer screening programs had been canceled in their countries, 68% reported delays or cancellations of surgery and other treatments, and 48% reported a drop in clinical trial participation. Additionally, 44% of organizations indicated they’ve seen a drop in urgent referrals for suspected cancer, and 44% said access to pathology services had been reduced.
• Roche announced that adding the PD-L1 inhibitor atezolizumab (Tecentriq) to bevacizumab (Avastin), paclitaxel, and carboplatin did not improve progression-free survival in women with newly diagnosed advanced ovarian cancer. The results came in the phase III IMagyn050 trial, which will continue gathering data on overall survival.

• Cellectis announced the FDA placed a hold on the MELANI-01 trial evaluating UCARTCS1A, an off-the-shelf chimeric antigen receptor (CAR) T-cell therapy to treat relapsed/refractory multiple myeloma, after a patient died from cardiac arrest. Cellectis is continuing trials of two other experimental off-the-shelf CAR T-cell therapies, UCART123 and UCART22.
• Genentech and Amgen settled two court cases involving biosimilars. Genentech filed the lawsuits to try to prevent Amgen from selling its trastuzumab biosimilar, trastuzumab-anns (Kanjinti), and its bevacizumab biosimilar, bevacizumab-awwb (Mvasi), in the United States. Genentech claimed that Amgen did not provide adequate notice before commercializing the drugs, but a federal court sided with Amgen in both cases.
• Based on the phase III ASCERTAIN trial, the FDA approved decitabine and cedazuridine (Inqovi; Astex Pharmaceuticals/Taiho Oncology/Otsuka Pharmaceutical) tablets for patients with myelodysplastic syndromes or chronic myelomonocytic leukemia. Patients can now take the hypomethylating agent orally rather than receiving it intravenously.
• Findings in The Lancet Oncology suggest that single-agent cabozantinib (Cabometyx; Exelixis) may be active in patients with metastatic urothelial carcinoma who have received prior therapies, including platinum-based chemotherapy. In a phase II trial, the agent elicited responses in eight of 42 patients; 19 more patients experienced stable disease. A tyrosine kinase inhibitor, cabozantinib is already approved for renal cell, hepatocellular, and thyroid cancers.

• Sanofi paid Kiadis $19.7 million in a deal that could be worth $971.3 million more in milestone payments. The deal centers on K-NK004, Kiadis’s investigational therapy that modifies natural killer cells to prevent the expression of CD38—and that is thought to amplify the effects of the CD38 inhibitor isatuximab-irfc (Sarclisa; Sanofi). Kiadis is conducting preclinical testing on K-NK004; Sanofi will take over once the agent enters clinical trials.
• In a deal with Merck, Foghorn Therapeutics will receive an undisclosed sum up front, and as much as $425 million more in milestone payments. Foghorn has 10 preclinical small molecule and protein degrader programs that target the chromatin regulatory system; Merck will gain the right to develop and commercialize any drugs the companies develop together.
• In JAMA Oncology, researchers reported that circulating tumor DNA (ctDNA) and circulating tumor cells (CTC) may predict recurrence of triple-negative breast cancer. In a randomized trial, 196 women with early-stage disease were tested for ctDNA and CTCs following neoadjuvant chemotherapy. Two years later, the rate of distant disease-free survival was 56% in those with ctDNA and 52% in those with ctDNA and CTCs, compared with 81% in women without ctDNA and 89% in those who were negative for both markers. The findings could help stratify patients in post-neoadjuvant trials.

• The FDA approved new indications for a few cancer drugs, including:

  • the PD-L1 inhibitor avelumab (Bavencio; EMD Serono) as a maintenance therapy for patients with locally advanced or metastatic urothelial carcinoma that has not worsened with first-line platinum-containing chemotherapy.
  • the PD-1 inhibitor pembrolizumab (Keytruda; Merck) for patients newly diagnosed with inoperable or metastatic microsatellite instability–high or mismatch repair–deficient colorectal cancer.
  • a combination of pertuzumab, trastuzumab, and hyaluronidase–ZZXF (Phesgo; Roche/Genentech) for patients with early or metastatic HER2-positive breast cancer. The triplet is injected under the skin and can be administered by a health care professional at a patient’s home.
• Seattle Genetics announced that a single-arm phase II trial of tisotumab vedotin showed a 24% objective response rate in 101 patients with recurrent or metastatic cervical cancer who were previously treated with chemotherapy; the median duration of response was 8.3 months. An antibody–drug conjugate, tisotumab vedotin homes to tissue factor, which is expressed in cervical cancer cells and can promote tumor growth, angiogenesis, and metastases.

• The NCI awarded 6 more years of funding to the NRG Oncology Biospecimen Bank (NRG-BB) and rated it as exceptional during the grant renewal process. The NRG-BB provides biospecimen support to the NCI National Clinical Trials Network by collecting, managing, and distributing annotated samples; currently its inventory includes 3,276,452 samples from 182,749 patients across 404 trials.
• Fred Hutchinson Cancer Research Center in Seattle, WA, laid off 76 administrative employees and nixed 81 open positions to help close a $50 million shortfall in revenue due to the COVID-19 pandemic. The institution had already implemented other cost-cutting measures, such as eliminating salary increases, reducing executive salaries by 5%, and limiting expenditures on consultants, in an effort to mitigate the downturn in philanthropic support and volatility in investment income. Many other cancer centers have taken similar steps in recent weeks.
• The NIH's National Human Genome Research Institute will spend $75 million over 5 years to create the Electronic Medical Records and Genomics (eMERGE) Genomic Risk Assessment and Management Network. The network, which will include 10 clinical sites, aims to establish protocols for better genomic risk assessments of disease in diverse populations that can be integrated into clinical care. The sites plan to recruit a total of 25,000 patients, focusing on those from racial or ethnic minority groups and underserved populations.

• During the Opening Ceremony of the American Association for Cancer Research (AACR) Virtual Annual Meeting II, Republican Senator Roy Blunt of Missouri emphasized the need for continued support for cancer research funding through the NIH and the NCI. "I’m a two-time cancer survivor myself—I understand the importance of cancer research," he said. He noted that federal support for cancer research has paid off, citing dozens of approvals for cancer drugs in the past year; major advances in the treatment of leukemia and prostate, breast, and lung cancers; and the development of immunotherapies.
• Also during the Opening Ceremony, the director of the FDA’s Oncology Center of Excellence, Richard Pazdur, MD, assured attendees that the agency’s oncology work hasn’t slowed despite the challenges posed by the COVID-19 pandemic. "From March through the end of May, we have approved eight new molecular entities and 23 new indications for a total of 31 approvals," Pazdur reported. "We remain committed during this most difficult time to expedite important new therapies for patients with cancer."
• In a series of AACR talks, researchers explored the underrepresentation of minority patients in clinical trials. Ajay Nooka, MD, MPH, of Emory University in Atlanta, GA, spoke about efforts there to increase participation of Black patients in multiple myeloma trials, and Ruben Mesa, MD, director of the Mays Cancer Center in San Antonio, TX, outlined work in southern Texas to improve accrual of Hispanic patients in all types of cancer trials. Among their strategies: partnering with community-based organizations, providing patients with culturally specific educational materials, and educating clinicians about barriers to trial participation and how to overcome them.
• "With crisis comes opportunity," said Paul Kluetz, MD, of the FDA, who spoke about modifications that have been made to cancer clinical trials to keep them running during the COVID-19 pandemic. For example, he said that the agency has embraced telemedicine and decentralization of trials so that patients can continue to participate without having to travel far from home. Whether the changes will become permanent is an open question, however. The agency will want evidence showing that "the grand experiment" will not have a negative effect on trial integrity, and that trial variability can be minimized.
• Jean-Yves Pierga, MD, PhD, of the Institut Curie in Paris, France, spoke at the AACR meeting about the UCBG COMET trial, which compared the prognostic value of circulating tumor cells with circulating tumor DNA for metastatic breast cancer. He concluded that the two approaches are more complementary than overlapping, with both biomarkers providing independent prognostic information and unique biological insights. Commenting on the findings, Jorge Reis-Filho, MD, PhD, of Memorial Sloan Kettering Cancer Center (MSKCC) in New York, NY, remarked that "the question remains as to how to optimally integrate these different types of data" to improve survival.
• During a session on racism and racial inequities at the AACR meeting, panelists discussed diversity within the cancer research community, including the lack of Black faculty at universities and cancer centers and lower funding rates for R01 grant applications from Black scientists. The group also delved into measures that could be taken to increase diversity, such as providing educational opportunities in science before college, proactively recruiting students into cancer research, offering incentives to institutions to hire minority faculty members, and increasing mentoring. "I refute that we don’t know how to get this done," said Robert Winn, MD, director of the Virginia Commonwealth University Massey Cancer Center in Richmond. "It’s not the issue that we don’t know, it’s the issue of will."
• Also at the AACR meeting: Investigators from Autolus Therapeutics and University College London, UK, reported on the multimodular chimeric antigen receptor (CAR) T-cell construct AUTO7, which is comprised of a PSMA binder, a safety switch, and modules that induce TGFβ1 resistance, block immune checkpoint–mediated immunosuppression, drive cytokine-mediated proliferation, and induce adjuvant activity with no toxicity. AUTO7 CAR T-cell treatment eradicated prostate tumors in vivo, providing evidence that a CAR T-cell therapy can work in an immunologically cold solid tumor. Based on these results, a phase I/II trial in prostate cancer is set to open in early 2021.
• At the AACR meeting, NIH Director Francis S. Collins, MD, PhD, outlined the agency’s activities in response to the COVID-19 pandemic, including the Rapid Acceleration of Diagnostics (RADx) initiative, which aims to accelerate innovation in and implementation of COVID-19 testing. He also announced funding opportunities for a new RADx component, RADx Underserved Populations (RADx-UP), a $500 million project to improve testing in vulnerable populations. "We’re counting on this to be a major initiative to address health disparities as they relate to COVID-19 and other things as well," Collins said.

• A new machine-learning approach called EcoTyper, described at the AACR meeting by Bogdan Luca, PhD, of Stanford University in California, provides insights into the heterogeneity and complex interactions among various cells in the tumor microenvironment: tumor cells, fibroblasts, endothelial cells, and various immune cells. EcoTyper deconvolutes cell type–specific gene-expression profiles from bulk tissue to define transcriptional states for each cell type and to identify patterns of cell states that co-occur across solid tumors. This approach yields a high-resolution picture of distinct tumor cellular ecosystems that may suggest strategies for improved diagnosis and therapy.
• Some common FOXA1 missense mutations are enriched in metastatic ER-positive breast cancer and associated with poorer response to endocrine therapy, according to a presentation at the AACR meeting by Amaia Arruabarrena-Aristorena, PhD, of MSKCC. Mechanistically, these mutations affect FOXA1’s chromatin-binding ability, increasing its estrogen stimulation–driven affinity for ER-target loci and promoting ER-dependent transcription. The FOXA1 hotspot mutations discovered in this work may help identify biomarkers of responsiveness to endocrine therapy and aid in designing new treatments.
• Described at the AACR meeting, the Cancer Cell Line Factory generates patient-derived cancer cell lines for broader representation of disease diversity, with the emphasis on less-common cancers. More than 200 biospecimens have been submitted directly by patients, 22% of which are from ethnic and racial minorities. The samples are cultured, in parallel, under 64 different 2-D culture conditions and 16 different 3-D conditions. With this approach, the researchers—from the Broad Institute of MIT and Harvard in Cambridge, MA, and Dana-Farber Cancer Institute in Boston, MA—have established 250 new models, including 42 genetically defined lines for rare cancers such as uveal melanoma, and are now characterizing their heterogeneity, sensitivity to drugs, and other factors; 120 models are currently available to researchers through https://hcmi-searchable-catalog.nci.nih.gov and the ATCC.
• Also at the meeting, Steven A. Rosenberg, MD, chief of surgery at the NCI, received the AACR–Cancer Research Institute Lloyd J. Old Award in Cancer Immunology. Rosenberg has devoted his career to developing immunotherapeutics. His major contributions to the field of immunotherapy have included treating patients with high-dose IL2, developing methods to expand patient-derived tumor-specific T cells, and setting the foundation for cellular adaptive transfer both for CAR T cells and T-cell receptor engineered T-cell therapies.
• The FDA approved selinexor (Xpovio; Karyopharm Therapeutics) for certain patients with relapsed/refractory diffuse large B-cell lymphoma based on an overall response rate of 29% in the phase IIb SADAL trial. Selinexor is a selective inhibitor of nuclear export that inhibits XPO1; it was previously approved for relapsed/refractory multiple myeloma.
• The agency also approved the PD-1 inhibitor pembrolizumab (Keytruda; Merck) in patients with recurrent or metastatic cutaneous squamous-cell carcinoma that cannot be treated with surgery or radiation. The approval was based on KEYNOTE-629, in which patients had an objective response rate of 34%.
• Invitae will acquire ArcherDX for $325 million in cash in a deal that could be worth up to $1.4 billion with milestone payments. In the deal, Invitae will gain access to Stratafide DX, ArcherDX’s pan-cancer companion diagnostic developed to identify genomic alterations in tissue and blood samples, as well as its Personalized Cancer Monitoring product, designed to assess how patients are faring on treatment and when their disease recurs.
• The FDA launched Project Patient Voice, an initiative that will gather data on patient-reported symptoms during cancer trials. The project will collect information from patient questionnaires completed during trials about disease- and treatment-related symptoms and enter the information into a freely available database.

• The FDA announced several approvals for oncology agents:

  • lurbinectedin (Zepzelca; PharmaMar/Jazz Pharmaceuticals), to treat adults with metastatic small-cell lung cancer who have received platinum-based chemotherapy. In a phase II basket trial, 105 patients had an overall response rate (ORR) of 30% and a median duration of response of 5.1 months. The approval is the first for lurbinectedin, a selective oncogenic transcription inhibitor.
  • gemtuzumab ozogamicin (Mylotarg; Pfizer), to treat children 1 month and older with newly diagnosed CD33-positive acute myeloid leukemia. The antibody–drug conjugate, which was already approved for the same indication in adults, was OK’d for pediatric patients based on safety and efficacy data from the AAML0531 trial.
  • the EZH2 inhibitor tazemetostat (Tazverik; Epizyme), to treat adults with relapsed/refractory follicular lymphoma who don’t have alternative treatment options, as well as those with relapsed/refractory disease whose tumors have an EZH2 mutation and who have already received at least two therapies. The approval was based on a phase II trial in which patients without EZH2 mutations had an ORR of 34% and those with EZH2 mutations had an ORR of 69%.
  • the PD-1 inhibitor pembrolizumab (Keytruda; Merck) in adults and children with inoperable or metastatic solid tumors that have a high tumor-mutation burden, and whose cancer has worsened on other therapies. These patients had an ORR of 29% in the KEYNOTE-158 trial. This is the second tumor-agnostic approval for pembrolizumab, which was previously approved in patients with mismatch repair–deficient or microsatellite instability–high tumors.

• GlaxoSmithKline (GSK) will pay Ideaya $100 million up front in a deal that could be worth up to $3 billion more in milestone payments. GSK will have the option to take on up to three of Ideaya’s synthetically lethal drug programs, one of which is developing a MAT2 inhibitor called IDE397. The other programs are developing agents that target DNA polymerase theta and Werner syndrome helicase.
• Looking to expand the scope of its liquid biopsy platforms, Foundation Medicine announced that it will acquire Lexent Bio. Lexent is developing a monitoring platform based on low-pass whole-genome sequencing and DNA methylation analysis. Foundation Medicine plans to incorporate these approaches into new assay platforms.
• To maintain trial integrity while mitigating the effects of the pandemic, the FDA released a draft guidance that provides statistical recommendations for trials affected by COVID-19. For example, the document offers strategies for handling loss of statistical power, analyzing data from trials that were stopped early, increasing enrollment after the pandemic, and deciding when and how to modify endpoints. The guidance is available for comment until July 16.
• Adding the ATR kinase inhibitor berzosertib (M6620; Merck) to gemcitabine may improve progression-free survival (PFS) in patients with recurrent, platinum-resistant high-grade serous ovarian cancer compared with gemcitabine alone. In a phase II trial reported in The Lancet Oncology, the combination extended median PFS by 8.2 weeks. Berzosertib is being investigated in other solid tumors, including breast, lung, and prostate cancers.

• Bristol-Myers Squibb announced that the FDA approved nivolumab (Opdivo) for patients with certain esophageal squamous cell carcinomas who have received fluoropyrimidine- and platinum-based chemotherapy. The decision was based on the phase III ATTRACTION-3 trial, in which patients treated with the PD-1 inhibitor had a median overall survival (OS) of 10.9 months, compared with 8.4 months in patients who received docetaxel or paclitaxel.
• AbbVie will pay Genmab $750 million up front in a deal that could be worth up to $3.2 billion more in milestone payments. Together, the companies will develop and commercialize three of Genmab’s early-stage bispecific antibody candidates, including the CD3/CD20-targeting agent epcoritamab, a CD3x5T4 antibody, and a drug that targets CD37. The companies will also develop up to four additional bispecifics.
• Innovent and Roche announced a partnership that could earn Roche more than $2 billion in milestone payments. The companies will combine Innovent’s cellular discovery platform with Roche’s CAR T-cell technology and T-cell bispecific antibody platform to identify, develop, and commercialize cell therapies and bispecific antibodies to treat cancer.
• The American Cancer Society announced it will lay off 1,000 employees to trim expenses. The organization has struggled with fundraising during the COVID-19 pandemic and is expecting a shortfall of at least $200 million this year. The layoffs, along with other cuts, will decrease the organization’s overall budget by around 30%.

• Merck's PD-1 inhibitor pembrolizumab (Keytruda) plus chemotherapy may not be effective in newly diagnosed advanced or metastatic urothelial cancer. In the phase III KEYNOTE-361 trial, the combination did not significantly improve OS or progression-free survival compared with chemotherapy alone.
• The American Society for Radiation Oncology released recommendations for using radiation therapy to treat nonmetastatic cervical cancer. The document states that there is strong evidence for the use of radiation therapy with or without chemotherapy as an initial therapy and after surgery; brachytherapy and intensity modulated radiation therapy are recommended in certain situations.
• The NIH published a guidance outlining steps the agency is taking to combat sexual harassment at grantee institutions. The guidance lays out expectations for reporting sexual harassment by a principal investigator whose work is funded by an NIH grant—including requiring institutions to report any time an investigator is removed from a project or seeks to take a grant to a new institution due to sexual harassment allegations.

• At the 2020 American Society of Clinical Oncology (ASCO) Annual Meeting, NCI Director Norman Sharpless, MD, spoke about the challenges of COVID-19 for cancer research and treatment, including disruptions to clinical trials. "Accrual to clinical trials has definitely slowed," he said, dropping by about half across the NCI’s National Clinical Trials Network in March and April, and decreasing in trials run by pharmaceutical companies. "Clinical trials are how we make progress for patients with cancer, and these decreases in accrual will translate into reduced new approaches for patients," he added. "We certainly hope that as circumstances permit, institutions and providers will resume accrual to ensure continued research progress."
• Adding enzalutamide to androgen-deprivation therapy (ADT) may improve survival in men with nonmetastatic, castration-resistant prostate cancer and rapidly rising PSA levels, according to findings presented at the ASCO meeting and simultaneously published in The New England Journal of Medicine (NEJM). In the phase III PROSPER trial, patients treated with enzalutamide plus ADT had a median overall survival (OS) of 67 months, compared with 56.3 months in patients who received only ADT.
• Also at the ASCO meeting, researchers reported that the oral gonadotropin-releasing hormone antagonist relugolix may be safer and better at suppressing testosterone levels in men with advanced prostate cancer than leuprolide, an injectable luteinizing hormone-releasing hormone agonist. In the phase III HERO trial, 96.7% of men treated with relugolix maintained castration through 48 weeks, compared with 88.8% of those receiving leuprolide; men in the relugolix group also had a 54% reduction in the incidence of major cardiovascular side effects. Results were concurrently published in NEJM.

• Roche’s ALK inhibitor alectinib (Alecensa) may be an effective first-line therapy against advanced ALK+ non–small cell lung cancer (NSCLC), researchers confirmed at the ASCO meeting. In an updated analysis of the phase III ALEX trial, patients treated with alectinib had a 5-year survival rate of 62.5%, compared with 45.5% in patients treated with crizotinib (Xalkori; Pfizer).
• Tepotinib may be effective in patients with advanced NSCLC who have MET exon 14 skipping mutations, according to findings presented at the ASCO meeting and published in NEJM. In a single-arm phase II study, 152 patients had a response rate of 46% and a median duration of response of 11.1 months. In total, 28% of patients had adverse events classified as grade 3 or higher, leading 11% to discontinue treatment.
• Based on the phase III IMbrave150 trial, the FDA approved the PD-L1 inhibitor atezolizumab (Tecentriq; Roche) plus the angiogenesis inhibitor bevacizumab (Avastin; Genentech) in patients with inoperable or metastatic hepatocellular carcinoma who have not received systemic therapy. In the trial, patients treated with the combination had a 12-month OS rate of 67.2% and a median progression-free survival (PFS) of 6.8 months, compared with 54.6% and 4.3 months, respectively, in patients who received standard sorafenib (Nexavar; Bayer/Onyx).
• The FDA also approved the EGFR inhibitor ramucirumab (Cyramza; Lilly) plus erlotinib in patients with newly diagnosed metastatic NSCLC who have EGFR exon 19 deletions or exon 21 mutations. The approval was based on the phase III RELAY trial, in which patients treated with the combination had a median PFS of 19.4 months, compared with 12.4 months in patients who received erlotinib alone.

• The FDA approved brigatinib (Alunbrig; Takeda) for patients with newly diagnosed metastatic non–small cell lung cancer (NSCLC) harboring ALK alterations. The approval was based on the phase III ALTA IL trial, in which patients treated with the agent had a median progression-free survival (PFS) of 24 months and an overall response rate of 74%, compared with 11 months and 62% in patients who received the ALK inhibitor crizotinib (Xalkori; Pfizer).
• Bristol-Myers Squibb (BMS) announced that the FDA approved nivolumab (Opdivo) plus ipilimumab (Yervoy) and platinum-doublet chemotherapy as a first-line therapy for patients with metastatic or recurrent NSCLC lacking EGFR or ALK alterations. In the phase III CHECKMATE-9LA trial, which formed the basis of the approval, patients treated with the PD-1–CTLA4 inhibitor combination had a median overall survival (OS) of 14.1 months and a median PFS of 6.8 months, compared with 10.7 months and 5 months, respectively, in patients who received only chemotherapy.
• Gilead paid Arcus Biosciences $375 million in a deal that could be worth up to $1.6 billion more in milestone payments. Arcus is developing immune checkpoint inhibitors that target PD-1 and TIGIT: Its leading candidates are the anti-TIGIT agent AB154, the A2AR/A2bR antagonist AB928, and the PD-1 inhibitor zimberelimab (AB122), all of which are in clinical trials. As part of the deal, which establishes a 10-year partnership between the companies, Gilead gains access to Arcus’s current and future immunotherapies.

• BMS inked a $65 million deal with Repare Therapeutics. The companies will use SNIPRx, Repare’s CRISPR-based, genome-wide synthetic lethal target discovery platform, to jointly identify synthetic lethal precision oncology targets for drug candidates; BMS will then further develop and commercialize drugs for these targets.
• Colonoscopies may be needed less frequently than thought, according to an observational study in the Annals of Internal Medicine. Researchers tracked 165,886 people between ages 50 and 65 at average risk of developing colorectal cancer. They found that a single negative colonoscopy was associated with reduced colorectal cancer incidence and mortality for up to 17.4 years. Currently, most guidelines recommend screening every 10 years for people at average risk.
• Syndax Pharmaceuticals announced that the HDAC inhibitor entinostat plus exemestane may not be effective in patients with advanced HR-positive, HER2-negative breast cancer who have already received a nonsteroidal aromatase inhibitor. In the phase III E2112 trial, the combination failed to extend OS compared with hormone therapy alone.

• It was another busy week for the FDA, which approved a spate of oncology agents for new indications:
  • the PD-1 inhibitor nivolumab (Opdivo; Bristol-Myers Squibb) plus the CTLA4 inhibitor ipilimumab (Yervoy; Bristol-Myers Squibb) as a first-line treatment for patients with metastatic non–small cell lung cancer (NSCLC) who express PD-L1 and who don’t have EGFR or ALK alterations. The approval was based on a subgroup analysis of the phase III CheckMate-227 trial, in which patients treated with the combination had a median overall survival (OS) of 17.1 months, compared with 14.9 months in patients who received chemotherapy. The agency also approved the PD-L1 IHC 28-8 pharmDx (Agilent Technologies) as a companion diagnostic.
  • the PD-L1 inhibitor atezolizumab (Tecentriq; Genentech) as a first-line therapy for patients with metastatic NSCLC who have high PD-L1 expression and who don’t have EGFR or ALK alterations. The approval was based on the IMpower110 trial, in which patients treated with the agent had a median OS of 20.2 months, compared with 13.1 months in patients who received chemotherapy. The agency also approved the Ventana PD-L1 Assay (Ventana Medical Systems) as a companion diagnostic.
  • the PARP inhibitor rucaparib (Rubraca; Clovis Oncology) for patients with BRCA-mutant metastatic castration-resistant prostate cancer who have already received androgen receptor–directed therapy and a taxane-based chemotherapy. The approval was based on the phase II TRITON2 trial, in which patients had an objective response rate of 44%. The agency also approved the BRACAnalysis CDx (Myriad Genetics) as a companion diagnostic.
  • the PARP inhibitor olaparib (Lynparza; AstraZeneca) for patients with metastatic castration-resistant prostate cancer who have homologous recombination repair gene alterations. The approval was based on the phase III PROfound trial, in which patients treated with the agent had a median radiologic progression-free survival (PFS) of 7.4 months and a median OS of 19.1 months, compared with 3.6 months and 14.7 months in patients who received standard enzalutamide or abiraterone acetate. The FDA also approved FoundationOne CDx (Foundation Medicine) as a companion diagnostic.

• • the KIT and PDGFRα inhibitor ripretinib (Qinlock; Deciphera Pharmaceuticals) for patients with advanced gastrointestinal tumors who have received at least three kinase inhibitors, including imatinib (Gleevec; Novartis). The approval was based on the phase III INVICTUS trial, in which patients treated with the drug had a median PFS of 6.3 months and a median OS of 15.1 months, compared with 1 month and 6.6 months in patients who received a placebo.
  • the antiangiogenic agent pomalidomide (Pomalyst; Celgene) for patients with AIDS-related Kaposi sarcoma whose disease does not respond to highly active antiretroviral therapy, or patients with Kaposi sarcoma who are HIV-negative. The approval was based on the phase I/II 12-C-0047 trial, in which patients had an overall response rate of 71% and a median duration of response of 21.1 months.
• Preliminary findings suggest that the Bruton tyrosine kinase inhibitor ibrutinib (Imbruvica; Janssen) may alleviate respiratory symptoms in patients with COVID-19 infections. Five patients taking a standard dose of ibrutinib for Waldenström macroglobulinemia who developed COVID-19 experienced no shortness of breath and did not require hospitalization; a sixth patient on a lower dose of ibrutinib was placed on a ventilator, but rapidly improved when the dose was increased. A clinical trial is testing ibrutinib in patients with moderate to severe COVID-19.
• The Cancer Prevention Research Institute of Texas in Austin awarded $56 million in grants to researchers at institutions in Texas, including The University of Texas MD Anderson Cancer Center in Houston and The University of Texas Southwestern Medical Center in Dallas. Grantees will use the money for research in areas such as positron emission tomography radiochemistry, oncogene addiction, and novel targeted agents.

• The FDA approved the RET inhibitor selpercatinib (Retevmo; LOXO-292; Lilly) in RET fusion–positive thyroid cancer and non–small cell lung cancer (NSCLC) and RET-mutant medullary thyroid cancer. The approval was based on the LIBRETTO-001 trial in which patients with previously treated and newly diagnosed NSCLC had overall response rates (ORR) of 64% and 85%, respectively. Patients with previously treated and newly diagnosed thyroid cancer had ORRs of 79% and 100% and those with previously treated and newly diagnosed medullary thyroid cancer had ORRs of 69% and 73%, respectively.

• The agency also approved the PARP inhibitor olaparib (Lynparza; AstraZeneca) plus bevacizumab as a maintenance therapy for patients with homologous recombination–deficient advanced epithelial ovarian, fallopian tube, or primary peritoneal cancers that have responded to chemotherapy. The approval was based on a subgroup analysis of the phase III PAOLA-1 trial, in which patients treated with the combination had a median progression-free survival of 37.2 months, compared with 17.7 months in patients who received bevacizumab alone. The agency also approved the myChoice CDx (Myriad) test as a companion diagnostic.

• Data published in JAMA Oncology suggest that children with cancer who get COVID-19 may not develop severe symptoms. At Memorial Sloan Kettering Cancer Center in New York, NY, 20 of 178 children with cancer tested positive for SARS-CoV-2. One patient required hospitalization due to COVID-19, and three others without significant COVID-19 symptoms were admitted for cancer-related reasons; the rest had mild symptoms that could be managed at home.

• COVID-19 is significantly disrupting cancer research, according to an American Cancer Society survey of 488 cancer researchers. Overall, 51% of respondents reported that their work is on hold due to COVID-19, and 59% said that laboratories at their institutions are closed. Additionally, 54% said they were working entirely remotely, and 91% said only essential personnel are allowed on campus.
• The FDA declined to review an application for idecabtagene vicleucel (ide-cel; Bluebird/Bristol-Myers Squibb) in multiple myeloma due to a lack of detail about how the product is manufactured. Ide-cel, formerly bb2121, is an experimental B-cell maturation antigen-directed chimeric antigen receptor T-cell therapy. The companies plan to resubmit the application with additional data on production.
• The FDA issued warning letters to two breast implant manufacturers for failing to comply with regulatory requirements. The agency sent a warning letter to Allergan for not conducting post approval studies on the long-term safety and risks of two models of breast implants—both of which were recalled last year after being linked to anaplastic large-cell lymphoma. The FDA also issued a warning letter to Ideal Implant Incorporated for not following manufacturing and adverse event reporting requirements.

• The FDA approved the MET inhibitor capmatinib (Tabrecta; Novartis) in patients with metastatic non–small cell lung cancer—including those with brain metastases—who have MET exon 14 skipping mutations. The approval is based on the phase II GEOMETRY mono-1 trial, in which newly diagnosed patients had an objective response rate (ORR) of 67.9% and patients who had received prior therapies had an ORR of 40.6%; patients with brain metastases had an ORR of 54%. The agency also approved the FoundationOne CDx assay as a companion diagnostic.
• According to a single-center study, patients with cancer may be more likely to die from COVID-19 than those without cancer. The study included 218 patients with cancer who tested positive for COVID-19 at Montefiore Medical Center in New York, NY. Sixty-one of those patients died, a mortality rate of 28%, which far exceeds the overall U.S. COVID-19 mortality rate of 5.8% reported by the World Health Organization.
• Sanofi/Regeneron announced that the PD-1 inhibitor cemiplimab (Libtayo) may be effective in patients with advanced basal cell carcinoma who relapsed on or were intolerant to a hedgehog pathway inhibitor. In a phase II trial, patients with locally advanced disease had an ORR of 29% and patients with metastatic disease had an ORR of 21%.

• Alexion Pharmaceuticals will acquire Portola Pharmaceuticals for $1.4 billion. Portola is known for its therapies to treat hematologic conditions, including the anticoagulants andexanet alfa (Andexxa) and betrixaban (Bevyxxa). The company is also developing cerdulatinib, a SYK/JAK inhibitor for blood cancers.
• The FDA also approved daratumumab and hyaluronidase-fihj (Darzalex Faspro; Janssen), a subcutaneous form of daratumumab, for patients with newly diagnosed or relapsed/refractory multiple myeloma. The approval was based on various trials that found the subcutaneous form performs similarly to the standard intravenous form, both alone and in combination with other agents.
• Due to the economic effects of the COVID-19 pandemic, Kura Oncology will discontinue development of KO-947, an ERK inhibitor in clinical testing for head and neck and esophageal squamous cell carcinomas. The company also announced that the pandemic will lead to delays in clinical trials of the farnesyltransferase inhibitor tipifarnib and the menin inhibitor KO-539.

• At the American Association for Cancer Research (AACR) Virtual Annual Meeting Part I, Haneen Shalabi, DO, of the NIH, reported that a chimeric antigen receptor T-cell therapy targeting CD19 and CD22 led to complete responses (CR) in five of 12 evaluable patients with relapsed or refractory acute lymphoblastic leukemia or non-Hodgkin lymphoma. All 13 treated patients experienced adverse effects, such as cytokine storm and neurotoxicity, all of which were manageable. Researchers had hypothesized that targeting both CD19 and CD22 would diminish the risk of antigen loss.
• "With a strong united community, we were able to activate a global registry and provide preliminary data in one month in the absence of dedicated funding," said Marina Chiara Garassino, MD, of the Fondazione IRCCS Istituto Nazionale dei Tumori in Milan, Italy, at the AACR meeting. She spoke about TERAVOLT, an international registry she helped create that includes data on patients with thoracic cancer who received treatment for COVID-19 infection. Among 200 patients included in the registry as of April 12, Garassino reported "an unexpectedly high mortality rate of 34.6%," but she noted a reporting bias and said that many patients had been receiving cancer treatment.
• Investigators reported at the meeting that, in contrast to what has been observed in NRAS-mutant melanoma, MEK inhibition has limited efficacy against other NRAS-mutant solid tumors. That was the conclusion of an NCI-MATCH study evaluating the MEK1/2 inhibitor binimetinib (Mektovi; Pfizer) to treat patients with refractory tumors harboring NRAS alterations. Of note, however, patients with codon Q61 NRAS-mutant tumors had longer progression-free and overall survival (OS) than patients with codon 12 or 13 NRAS-mutant tumors; the reasons for this difference aren’t clear.
• Researchers at the AACR meeting reported that Spectrum Pharmaceuticals’ EGFR inhibitor poziotinib may be modestly effective in patients with non–small cell lung cancer (NSCLC) who have EGFR exon 20 insertions. In a phase II trial of 115 patients, the agent elicited an objective response rate (ORR) of 14.8%, which did not meet the cutoff for significance. However, 68.7% of patients responded or experienced stable disease, and 65% experienced tumor shrinkage. Overall, 68% of patients required dose reductions and 10% discontinued treatment due to side effects.
• Genentech’s PD-L1 inhibitor atezolizumab (Tecentriq) plus enzalutamide may not be effective in treating metastatic castration-resistant prostate cancer (mCRPC), researchers announced at the AACR meeting. In the phase III IMbassador 250 trial, the combination did not improve OS or radiographic progression-free survival (PFS) compared with enzalutamide alone; the trial will be halted early due to the lack of efficacy. During her commentary, Padmanee Sharma, MD, PhD, of The University of Texas MD Anderson Cancer Center in Houston, highlighted the immunologically cold nature of mCRPC as a potential reason for the lack of benefit.
• Zotatifin (eFT226; eFFECTOR) may inhibit the growth of tumor cells that express FGFR1/2 or HER2, according to preclinical findings that were presented at the AACR meeting. In vitro, the agent inhibited tumor cell proliferation and induced apoptosis, resulting in tumor inhibition and regression across solid tumor xenograft models driven by FGFR1/2 or HER2amplification. Zotatifin, a small-molecule inhibitor of the eukaryotic translation initiation factor eIF4A, selectively downregulates the translation of mRNAs enriched for 5’UTR polypurine motifs, which include FGFR1/2 and HER2.

• Also at the AACR meeting, researchers reported variations in BRAF mutations across tumor types and based on co-occurring mutations. An analysis of more than 47,000 patients in the AACR Project GENIE database with a high-throughput BRAF-activity assay also revealed that active yet uncharacterized BRAF mutations represent about 10% of non–BRAF V600 mutations.
• Based on research that was presented at the AACR meeting, the FDA approved a new dosing regimen for pembrolizumab (Keytruda; Merck)—400 mg every 6 weeks—in adults treated with the drug for any approved indication. Researchers reported that in the KEYNOTE-555 trial, patients with metastatic melanoma who received this intravenous dose of the PD-1 inhibitor every 6 weeks exhibited pharmacokinetics and an overall response rate in line those observed for similar dosing schedules in previous trials: KEYNOTE-001, -006, and -252. The findings suggest that high flat doses could mean fewer treatments for patients.
• The molecular structure of mobocertinib (TAK-788) was disclosed for the first time, the day after the agent received FDA breakthrough therapy designation for the treatment of patients with NSCLC with EGFR exon 20 insertion mutations. In a phase I dose-escalation trial, objective responses were observed in seven of 18 patients with EGFR exon 20 mutations (six partial responses and one CR). A phase II dose-expansion trial is ongoing.
• Interest is expanding beyond PARP1/2 to other members of the large protein family, which differ enzymatically and affect distinct cellular stress responses. According to Laurie Schenkel, PhD, of Ribon Therapeutics, who reported on the company’s PARP14 inhibitor (RBN012759) at the meeting, "the mono-PARPs are relatively understudied and offer a mechanistically distinct and untapped opportunity." As early indicators of its therapeutic potential, the compound decreases the immunosuppressed phenotype of human macrophages treated with IL4 and induces changes in gene expression similar to immune checkpoint inhibition in some primary human tumor explants.
• The FDA approved niraparib (Zejula; GlaxoSmithKline) as a maintenance therapy in women with advanced epithelial ovarian, fallopian tube, or primary peritoneal cancer who responded to platinum-based chemotherapy. The approval was based on the phase III PRIMA trial, in which women treated with the PARP inhibitor had a median PFS of 13.8 months, compared with 8.2 months in women receiving a placebo.
• Due to their drug’s impressive efficacy, Regeneron and Sanofi will halt a phase III trial testing the PD-1 inhibitor cemiplimab (Libtayo) in patients with newly diagnosed advanced or metastatic NSCLC who tested positive for PD-L1 in at least half their tumor cells. The decision was based on the recommendation of an independent data-monitoring committee after the agent decreased the risk of death by 32.4% compared with chemotherapy.

It was a busy week for the FDA, which approved several drugs for cancer indications:

• the tyrosine kinase inhibitor tucatinib (Tukysa; Seattle Genetics) plus trastuzumab (Herceptin; Genentech) and capecitabine for certain patients with locally advanced inoperable or metastatic HER2-positive breast cancer. The approval was based on the phase II HER2CLIMB trial, in which patients treated with the tucatinib combination had a median progression-free survival (PFS) of 7.8 months and a median overall survival (OS) of 21.9 months, compared with 5.6 months and 17.4 months, respectively, in patients who received trastuzumab and capecitabine alone.
• the antibody–drug conjugate sacituzumab govitecan-hziy (Trodelvy; Immunomedics) for patients with metastatic triple-negative breast cancer who have received prior therapies. The approval was based on a phase II trial in which the drug elicited an overall response rate (ORR) of 33.3% and a median duration of response of 7.7 months. Sacituzumab govitecan-hziy consists of a monoclonal antibody against human trophoblast cell-surface antigen 2 conjugated to the topoisomerase I inhibitor SN-38.
• the fibroblast growth factor receptor (FGFR) inhibitor pemigatinib (Pemazyre; Incyte) for patients with inoperable locally advanced or metastatic cholangiocarcinoma who have FGFR2 fusions or other rearrangements and have received other therapies. The approval was based on the phase II FIGHT-202 trial, in which 107 patients had an ORR of 36; 63% of responses lasted for at least 6 months. The FDA also approved FoundationOne CDx (Foundation Medicine) as a companion diagnostic.
• the Bruton tyrosine kinase inhibitor ibrutinib (Imbruvica; AbbVie) plus rituximab (Imbruvica; Janssen) as a first-line therapy for chronic lymphocytic leukemia and small lymphocytic leukemia. The approval was based on the phase III E1912 trial, in which patients treated with the combination had a statistically significant improvement in PFS compared with those who received rituximab plus standard chemotherapy; median PFS was not reached in either arm.

• A survey of 32 cancer centers revealed how the COVID-19 pandemic is disrupting clinical trials. Overall, 54.8% of centers reported that patients are less willing to visit trial sites; 45.2% reported a reduction in staff to handle trials, and 38.7% reported issues with protocol compliance, delays in scheduling, or providing routine services.
• Due to the COVID-19 pandemic, the U.S. District Court for the District of Maryland extended the deadline for FDA review of new tobacco products. Now, manufacturers must submit applications for premarket review of electronic cigarettes and other new tobacco products to the FDA by September 9. The 120-day extension was granted due to disruptions for manufacturers preparing applications, as well as constraints at the FDA as staff are deployed to work on COVID-19.
• Adults with early-onset colorectal cancer may be diagnosed earlier if they are screened based on family history, according to a study in Cancer. Researchers analyzed data from patients ages 40 to 49 with colorectal cancer between 1998 and 2007. They found that 25% of patients met family history–based screening criteria, and, of those patients, 98.4% could have had their disease diagnosed sooner with earlier screening.

• The FDA will continue review activities during the COVID-19 pandemic. The New Drug Program, the Generic Drug Program, and the Biologics and Biosimilars Programs are still meeting to review drugs and biologics, and the Center for Devices and Radiological Health is continuing to meet to review devices. However, in making this announcement, the FDA cautioned that with many staff working on COVID-19 activities, it may not continue review activities at the same rate indefinitely.
• AstraZeneca will unblind a trial testing the EGFR inhibitor osimertinib (Tagrisso) as an adjuvant treatment for EGFR-mutant non–small cell lung cancer due to the drug’s promising efficacy. The move was recommended by an independent data-monitoring committee based on disease-free survival results in the phase III ADURA trial.
• The FDA approved the MEK inhibitor selumetinib (Koselugo; AstraZeneca) for children age 2 and older with neurofibromatosis type 1 who have symptomatic, inoperable plexiform neurofibromas. The approval was based on the single-arm SPRINT trial, in which the drug elicited an overall response rate of 66%, and 82% of responses lasted for at least 12 months.
• The agency also released a final guidance on broadening indications for oncology companion diagnostics. The guidance recommends broadening indications for these tests so they can be used to match patients not only to specific treatments, but also to similar drugs—for example, agents approved for the same indications or those that target the same molecular alterations.

• Two companies launched trials of Bruton tyrosine kinase (BTK) inhibitors to treat respiratory symptoms in patients with COVID-19 infections: AstraZeneca initiated a phase II trial of acalabrutinib (Calquence), and BeiGene launched a phase II trial of zanubrutinib (Brukinsa). Both BTK inhibitors are FDA approved for certain blood cancers.
• The American Society of Clinical Oncology (ASCO) launched a registry of patients with cancer who are infected with COVID-19. Open to all U.S. oncology practices, the ASCO Survey on COVID-19 in Oncology Registry is gathering baseline and long-term data on symptoms and treatment in these patients, as well as details on how they fared.
• The FDA approved mitomycin gel (Jelmyto; UroGen Pharma) as a first-line therapy for low-grade upper-tract urothelial cancer based on the phase III OLYMPUS trial. In that study, the gel elicited a complete response in 41 of 71 patients, 19 of whom continued to respond at 12 months.

• Array BioPharma announced that the FDA approved encorafenib (Braftovi) plus cetuximab (Erbitux; Lilly) in patients with metastatic colorectal cancer who have a BRAF V600E mutation and have received prior therapy. The approval is based on the phase III BEACON CRC trial, in which patients treated with the combination had a median overall survival of 8.4 months and a median progression-free survival of 4.2 months, compared with 5.4 months and 1.5 months, respectively, in patients who received cetuximab plus standard chemotherapy.
• The agency also approved luspatercept-aamt (Reblozyl; Celgene) to treat anemia in certain patients with myelodysplastic syndromes The approval was based on the phase III MEDALIST trial, in which 38% of patients treated with the agent did not require a red blood cell transfusion for at least 8 weeks, compared with 13% of those who received a placebo.
• Janssen Biotech will pay Fate Therapeutics $50 million up front and $50 million in equity in a deal that could be worth up to $3 billion in milestone payments. The companies will develop novel chimeric antigen receptor (CAR) natural killer cell and CAR T-cell candidates by combining Fate’s induced pluripotent stem cell platform with Janssen’s tumor-targeting antigen binders.

• Health-related organizations urged the White House to work to alleviate the shortage of ventilators and personal protective equipment that has resulted from the COVID-19 pandemic. In a letter, more than 200 groups asked the government to facilitate timely manufacturing and distribution of these products through a transparent, equitable, and noncompetitive process that is also based on need. The letter was signed by the American Lung Association, the Association of American Cancer Institutes, and the Leukemia & Lymphoma Society, among others.
• An article on safety for patients and healthcare workers during the COVID-19 pandemic was published in The Journal of the National Comprehensive Cancer Network. The feature makes recommendations such as screening patients for COVID-19 before visits, implementing alternative dosing schedules, and allowing staff to work remotely when possible. Other cancer organizations are also offering recommendations for dealing with COVID-19, including the American Society of Clinical Oncology, the Society of Surgical Oncology, and the American Society for Radiation Oncology.
• Following a recommendation from an independent monitoring committee, Immunomedics announced it will halt the phase III ASCENT trial testing sacituzumab govitecan (IMMU-132) in metastatic triple-negative breast cancer due to the drug’s impressive efficacy. An antibody–drug conjugate that targets TROP2, sacituzumab govitecan earned the FDA’s fast track designation.

• The FDA updated guidances to address the shortage of blood donations during the COVID-19 pandemic. The guidances collectively broaden the population eligible to donate blood by shortening or eliminating the deferral period for certain people, such as those with recent tattoos and piercings or those who have recently traveled to areas with malaria. The Red Cross has been issuing pleas and running ads to encourage the general public to donate blood.
• The agency also approved durvalumab (Imfinzi; AstraZeneca) plus chemotherapy as a first-line treatment for extensive-stage small cell lung cancer. The approval was based on the phase III CASPIAN trial, in which patients treated with the combination had a median overall survival of 13 months, compared with 10.3 months in patients who received chemotherapy alone. A PD-L1 inhibitor, durvalumab was previously approved for certain types of non–small cell lung cancer and bladder cancer.
• Kite’s experimental anti-CD19 chimeric antigen receptor T-cell therapy KTE-X19 may be effective in patients with relapsed/refractory mantle-cell lymphoma who have previously received a Bruton tyrosine kinase inhibitor, researchers reported in The New England Journal of Medicine. In a phase II trial, the therapy elicited a response in 93% of 60 patients, and 57% of patients were in remission at a median follow-up of 12.3 months.

• An international data registry was launched to help medical professionals care for patients with blood cancers and COVID-19. The American Society of Hematology Research Collaborative’s Data Hub COVID-19 Registry for Hematologic Malignancy is designed to allow providers to easily share and access deidentified clinical data on patients with blood cancers who test positive for COVID-19, nearly in real time.
• Cancer agents are increasingly being considered as potential treatments for COVID-19. For example, Sanofi and Regeneron launched two trials testing their IL6 inhibitor sarilumab (Kevzara) in patients with COVID-19. Additionally, at least 10 patients with COVID-19 have been treated with the CCR5 antagonist leronlimab (PRO 140; CytoDyn) at New York Medical Center in New York, NY.
• The FDA requested the removal of all ranitidine drugs from the market due to the possible presence of a carcinogen called N-Nitrosodimethylamine. Ranitidine, which blocks acid production in the stomach, is used to treat conditions such as heartburn, ulcers, and acid reflux. The carcinogen is an impurity in the drug that appears to increase over time and when the drug is stored at higher temperatures.

• Patients with cancer admitted to the hospital may have a higher likelihood of being infected with SARS-CoV-2 than the general population, according to findings in JAMA Oncology. Researchers analyzed medical records from 1,524 patients with cancer admitted to Zhongnan Hospital of Wuhan University in China in early 2020. They found that 0.79% of patients at the hospital became infected with SARS-CoV-2, compared with 0.37% of people in the community.
• As the COVID-19 pandemic continues, more cancer conferences are being postponed or conducted online. The 2020 World Conference on Lung Cancer has been postponed until January 2021, and the 2020 American Society of Clinical Oncology Annual Meeting will be entirely virtual (dates to be announced). The American Association for Cancer Research Annual Meeting 2020 has been postponed—likely until August—but the organization will host a virtual meeting preview starting April 27 that includes basic and clinical research presentations.
• A study in The Lancet Oncology suggests that prostate-specific membrane antigen (PSMA) PET-CT may be better at identifying metastases in men with prostate cancer than CT and bone scans. Researchers assigned 302 men to undergo either PMSA PET-CT or standard CT and bone scans. They found that PMSA PET-CT was more accurate at detecting metastases than conventional imaging—92% vs. 65%, respectively.

• The Japanese Ministry of Health, Labour, and Welfare approved the MET inhibitor tepotinib (Tepmetko; Merck) to treat patients with inoperable, advanced, or recurrent non–small cell lung cancer who have MET exon 14 skipping alterations. The approval was based on the phase II VISION trial, in which the agent elicited an objective response rate of 42% and a median duration of response of 12 months.
• Tolero Pharmaceuticals announced it will join the Beat AML Master Trial, a multiarm umbrella trial run by the Leukemia and Lymphoma Society in which patients newly diagnosed with acute myeloid leukemia (AML) are matched to targeted agents based on genomic sequencing of tumors. Tolero’s AXL receptor tyrosine kinase inhibitor dubermatinib will be available to patients with TP53 mutations and/or complex karyotype.
• The FDA issued a warning about the risk of SARS-COV-2 transfer through fecal microbiota transplantation. The agency made several recommendations to prevent transfer of the virus, including screening donors for exposure, testing donors for the virus, and developing exclusion criteria. Fecal microbiota transplantation is being investigated as a strategy to improve the success of allogeneic hematopoietic-cell transplants in patients with blood cancer.

• The FDA released a guidance on conducting clinical trials during the COVID-19 pandemic. It outlines recommendations for running trials, including assessing patients through alternative means, offering additional safety monitoring to patients who can no longer travel to the trial site, and adjusting trial protocols. “The FDA is helping industry and investigators navigate the COVID-19 pandemic and help assess how to move forward with critical clinical trials,” said Anand Shah, MD, the FDA deputy commissioner for medical and scientific affairs.
• The agency also issued a final rule requiring new health warnings on cigarette packages and advertisements that consist of text and images of lesser-known health risks of smoking, such as cardiac disease and diabetes. Beginning in June 2021, the warnings must cover 50% of the area on the front and back of cigarette packages, and at least 20% of the area at the top of cigarette advertisements.
• A study in JAMA Oncology revealed that germline mutations may be more common in children with osteosarcoma than previously thought. Researchers performed next-generation exome sequencing on 1,244 patients with the disease and found that 28% had a rare pathogenic or likely pathogenic germline variant in a cancer-susceptibility gene, compared with 12.1% of healthy people. The findings could lead to more genomic testing and counseling of patients and their families.

• The National Comprehensive Cancer Network (NCCN) updated clinical practice guidelines for prostate cancer to recommend biomarker testing for patients with unfavorable intermediate- or high-risk disease who have a life expectancy of at least 10 years. The new guidelines recommend that these patients consider being tested with the Prolaris test (Myriad Genetics) or the Decipher test (GenomeDx Biosciences), both of which assess the cancer’s aggressiveness. Previously, the NCCN did not recommend routine testing in these groups.
• AstraZeneca announced that Japan granted orphan drug designation to olaparib (Lynparza) for maintenance treatment of patients with inoperable BRCA-mutated pancreatic cancer. The decision was based on the phase III POLO trial, in which patients treated with the PARP inhibitor had a median progression-free survival of 7.4 months, compared with 3.8 months in patients who received a placebo. The FDA approved the therapy for a similar indication in late 2019.

• The American Association for Cancer Research has terminated its 2020 Annual Meeting, originally planned for April 24–29 in San Diego, CA. The conference will be rescheduled for later this year. Other major meetings have also been postponed or canceled, including the European Breast Cancer Conference and the Society of Gynecologic Oncology Annual Meeting.
• Bristol-Myers Squibb announced that the FDA approved nivolumab (Opdivo) plus ipilimumab (Yervoy) for patients with hepatocellular carcinoma who previously received or cannot tolerate sorafenib. The decision was based on the phase I/II CheckMate-040 trial, in which 49 patients treated with the combination had an objective response rate of 33%.
• The agency also issued a draft guidance on increasing the representation of adults 65 and older in cancer clinical trials, noting that these patients may have different drug responses, side effects, and coexisting conditions than younger patients. The guidance makes several recommendations for sponsors, including adapting trial design to accommodate older patients, developing recruitment strategies that target this group, and collecting additional information from these patients. The document is available for comment until May 5.
• Thermo Fisher Scientific and Janssen will develop a test that supports enrollment in cancer clinical trials. Initially, the companies will validate biomarkers that can be used with Thermo Fisher’s existing Oncomine Dx Target Test to identify patients with non–small cell lung cancer who are eligible for trials; they may later expand into other cancers. The test is a next-generation sequencing assay that covers 46 cancer biomarkers.

• AstraZeneca and Merck announced that cediranib (Recentin) plus olaparib (Lynparza) may not be effective in patients with platinum-sensitive relapsed ovarian cancer. In the GY004 trial, the VEGFR inhibitor/PARP inhibitor combination did not extend median progression-free survival compared with platinum-based chemotherapy.
• The FDA placed a partial hold on Unum’s phase I trial testing ACTR707 plus rituximab (Rituxan; Genentech) in CD20-positive, B-cell non-Hodgkin lymphoma. The decision was made after a patient developed a serious side effect that could be a new malignancy. ACTR707, an experimental autologous T-cell therapy, is also being tested in combination with trastuzumab (Herceptin; Genentech) in patients with HER2-positive cancers.
• Henry Ford Health System received a $25 million donation that will support the creation of a Precision Health Center. The center will focus on studying the genetic underpinnings of cancer, including genomic markers that can reveal mutational patterns in tumor cells.
• The UK’s National Institute for Health and Care Excellence (NICE) recommended against polatuzumab vedotin (Polivy; Genentech) plus rituximab and bendamustine in patients with relapsed/refractory diffuse large B-cell lymphoma who can’t have a transplant. NICE also recommended against pembrolizumab (Keytruda; Merck) in patients with locally advanced or metastatic urothelial carcinoma who have received prior chemotherapy. The agency cited a lack of data on the long-term benefit of the treatments, making their cost-effectiveness unclear.

• Thermo Fisher Scientific announced it will buy Qiagen for $11.5 billion. In oncology, Qiagen is known for its companion diagnostics, including tests that detect KRAS mutations in colorectal cancer and EGFR mutations in lung cancer, to identify patients who may respond to targeted therapies. Thermo Fisher will also obtain Qiagen’s sample preparation, digital PCR, and bioinformatics technologies.
• Major cancer centers have announced that they will suspend professional travel due to COVID-19 and recommended against personal travel, citing concerns about exposing patients to the virus. So far, the list includes institutions such as The University of Texas MD Anderson Cancer Center in Houston and Dana-Farber Cancer Institute in Boston, MA; Fred Hutchinson Cancer Research Center in Seattle, WA, is requiring employees to work remotely. Organizations such as the National Comprehensive Cancer Network are also canceling or postponing conferences.
• Gilead will buy Forty Seven for $4.9 billion. In the deal, Gilead will gain access to Forty Seven’s anti-CD47 agent magrolimab, which is being tested in several blood cancers, including acute myeloid leukemia (AML) and diffuse large B-cell lymphoma. Forty Seven is also developing antibodies that target SIRPα and cKIT.
• The FDA approved isatuximab-irfc (Sarclisa; Sanofi) plus pomalidomide (Pomalyst; Celgene) and dexamethasone in patients with multiple myeloma who have received at least two prior therapies, including lenalidomide and a proteasome inhibitor. The approval was based on the phase III ICARIA-MM trial, in which patients who received the triplet had a median progression-free survival (PFS) of 11.5 months, compared with 6.5 months in patients who received a pomalidomide—dexamethasone regimen. Isatuximab-irfc targets CD38.

• The XPO1 inhibitor selinexor (Xpovio; Karyopharm Therapeutics) plus bortezomib (Velcade; Millennium) and dexamethasone may improve outcomes in patients with multiple myeloma who have received one to three therapies. In the phase III BOSTON trial, patients in the selinexor group had a median PFS of 13.9 months, compared with 9.5 months in patients who received bortezomib plus dexamethasone. Selinexor has already been approved for patients with multiple myeloma who had received at least four prior therapies based on the phase II STORM trial.
• AbbVie announced that venetoclax (Venclexta) plus low-dose cytarabine may not be effective in newly diagnosed patients with AML who aren’t eligible for intensive chemotherapy. In the phase III VIALE-C trial, the combination did not improve overall survival compared with cytarabine alone. A BCL2 inhibitor, venetoclax is approved to treat certain patients with newly diagnosed AML based on a phase I trial.
• The Count Me In initiative launched the Osteosarcoma Project, a research effort that will rely on social media to enroll large numbers of patients with the disease and create extensive—and freely available—online databases of clinical and genomic information. The project is one of several under the Count Me In umbrella, including projects in metastatic breast cancer, metastatic prostate cancer, and angiosarcoma.

• The FDA approved the tyrosine kinase inhibitor neratinib (Nerlynx; Puma) plus capecitabine for patients with advanced or metastatic HER2-positive breast cancer who have received at least two prior HER2-targeted treatments for metastatic disease. The approval was based on the phase III NALA trial, in which patients treated with the combination had a median progression-free survival (PFS) of 5.6 months and a median overall survival (OS) of 21 months, compared with 5.5 months and 18.7 months, respectively, in patients who received lapatinib plus capecitabine.
• The agency also announced steps to improve the safety of laparoscopic power morcellators (LPM) used during certain gynecologic surgeries. The agency released a draft guidance outlining safety information that should be added to labeling for LPMs, as well as a safety communication recommending that LPMs be used only in women undergoing myomectomy or hysterectomy who are under age 50 and have not reached menopause. The devices should be used with a containment system, such as PneumoLiner, which has received marketing authorization. LPMs have been known to spread occult cancer during gynecologic surgery.
• In a 13 to 2 vote, members of an FDA advisory committee recommended against approval of the ablation treatment padeliporfin dipotassium (Tookad; Steba) for localized, early-stage prostate cancer, citing poor trial design and execution and a lack of follow-up data showing that the treatment is more effective than active surveillance. The committee also voted 6 to 5 in support of ramucirumab (Cyramza; Lilly) plus erlotinib (Tarceva; Astellas) to treat patients with newly diagnosed metastatic EGFR-mutant non–small cell lung cancer. The panel was split on whether an improvement in PFS was enough to recommend the combination given a lack of improvement in OS. Although the FDA usually follows the panel’s advice, its recommendations are nonbinding.

• Genentech will pay Bicycle Therapeutics $30 million up front in a deal that could be worth up to $1.7 billion in milestone payments. Together, the companies will develop and commercialize immunotherapies for cancer that use Bicycle’s bicyclic peptide technology. Bicycle will focus on discovery and early preclinical development of candidates, and Genentech will tackle additional development and commercialization.
• Abbreviated MRI may be more effective than digital breast tomosynthesis (DBT), also called 3-D mammography, at detecting breast cancer in certain women, according to findings in JAMA. Using both MRI and DBT, researchers screened 1,444 women ages 40 to 75 found to have dense breasts during prior screening. They found that MRI detected 22 out of 23 cases of breast cancer, whereas DBT detected only nine cases.
• The FDA is launching a resource to help researchers access historical information about drug approvals. The Compilation of Center for Drug Evaluation and Research New Molecular Entity Drug and New Biologic Approvals is a freely available .CSV file that includes curated data on drugs approved by the agency since 1985.
• The American Association for Cancer Research (AACR) will receive $2 million from MPM Capital’s UBS Oncology Impact Fund (OIF). The funds, which will support basic and translational cancer research, add to an inaugural $1.2 million the AACR received from UBS OIF in 2018. The AACR-MPM Oncology Charitable Foundation Transformative Cancer Research Grants Program previously announced that it will award $800,000 in grants to early-career investigators.

• Merck’s HIF2α inhibitor MK-6482 may be effective in patients with advanced clear cell renal cell carcinoma who have received at least one prior therapy, according to findings presented at the 2020 Genitourinary Cancers Symposium in San Francisco, CA, February 13–15. In a phase I/II trial of 55 patients, 23.6% responded to the drug, and an additional 56.4% had stable disease; the median progression-free survival (PFS) was 11 months. MK-6482 is being tested in a phase III trial.
• Also at the symposium, researchers reported that the PARP inhibitor talazoparib (Talzenna; Pfizer) may be a promising therapy for patients with metastatic castration-resistant prostate cancer and DNA damage repair deficiency who previously received docetaxel. In a phase II trial, 81 patients with DNA damage repair mutations had an objective response rate (ORR) of 25.6% and a median PFS of 5.6 months; patients with BRCA1/2 mutations had an ORR of 50% and a median PFS of 8.2 months.
• GlaxoSmithKline (GSK) will pay Immatics $45 million up front to jointly develop two T-cell receptor therapies for solid tumors, and up to $550 million more in milestone payments. The companies will initially focus on autologous T-cell therapies, with the option of also co-developing allogeneic versions. Immatics will be responsible for early candidate development and validation; GSK will take on further manufacturing and commercialization.
• Cellectis made a $10 million deal with Servier that could be worth up to another $140 million in milestone payments, for each of six gene-edited allogeneic CAR T-cell therapies the companies co-develop. Per the deal, Cellectis will handle research and development of candidates, which include the CD19 inhibitor ALLO-501A, through phase I trials. At that point, Servier can opt to take over clinical development, registration, and commercialization.

• A study in the Journal of Clinical Oncology revealed that the rate of newly identified BRCA1/2 mutations in patients with pancreatic cancer may vary based on geography and race. Researchers conducted a retrospective analysis of geographic/demographic data from 2,206 patients with metastatic pancreatic cancer screened for the phase III POLO trial. They found that among 128 patients with newly identified BRCA1/2 mutations, the mutation rate was highest in U.S. patients (9.5%) and patients of African American descent (10.7%).
• China’s National Medical Products Administration approved atezolizumab (Tecentriq; Roche) plus chemotherapy in patients with newly diagnosed extensive-stage small cell lung cancer. The approval was based on the phase III IMpower133 trial, in which patients treated with the combination had a median overall survival of 12.3 months and a median PFS of 5.2 months, compared with 10.3 months and 4.3 months in patients who received chemotherapy alone.
• Five Prime Therapeutics announced that their investigational CSF1 inhibitor cabiralizumab plus nivolumab (Opdivo; Bristol-Myers Squibb) may not be effective in patients with advanced pancreatic cancer. In a phase II trial, the combination, with or without chemotherapy, failed to extend median PFS compared with chemotherapy alone.

• The Trump administration’s budget proposal for fiscal year (FY) 2021 includes an 8% cut to the NIH, from $41.6 billion to $38 billion. The proposal would also decrease the NCI budget from $6.25 billion to $5.69 billion. The NIH budget increased by $2 billion in FY2019 and by $2.5 billion in FY2020.
• The budget proposal also calls for ending the FDA’s authority to regulate tobacco products. Instead, a new agency would be formed within the Department of Health and Human services that focuses solely on tobacco-related issues, including electronic cigarettes. According to the proposal, "a new agency with the singular mission on tobacco and its impact on public health would have greater capacity to respond strategically to the growing complexity of new tobacco products."
• Cardiovascular problems that happen during oncology clinical trials are often not reported, according to a study in the Journal of the American College of Cardiology. Researchers analyzed data from 189 phase II and III cancer trials and found that only 62.4% reported any instances of cardiovascular events. Further, these trials had a much lower rate of such events than would be expected in the general population (542 versus 1,408, respectively, per 100,000 person-years), suggesting that problems are underreported.

• A single dose of the human papillomavirus vaccine may protect against cervical cancer in certain groups, researchers reported in Cancer. In a retrospective study, girls ages 15 to 19 who had previously received one dose of the vaccine had a similar incidence of precancerous cervical lesions as those who had received two or three doses.
• Marker Therapeutics announced that the FDA lifted a clinical hold on a trial testing a novel MultiTAA T-cell therapy in acute myeloid leukemia. The FDA placed the hold in November 2019 to request additional information about reagents used during the manufacturing process. The therapy is made by expanding naturally occurring, tumor-specific T cells present in a patient’s blood.
• A study in The BMJ reveals that smartphone applications for detecting skin cancer may not be accurate. Researchers analyzed nine studies that evaluated six algorithm-based smartphone apps and found that the apps had variable and unreliable results that did not match up well with expert recommendations—for example, they often could not determine whether low-risk lesions were benign. Researchers recommend that healthcare professionals inform patients about the limitations of the apps.

• A collection of 23 papers providing a comprehensive analysis of whole cancer genomes was published in Nature and its affiliated journals. In the Pan-Cancer Analysis of Whole Genomes Project, more than 1,300 researchers from 37 countries analyzed more than 2,600 whole cancer genomes from 38 tumor types and their matching normal tissues. Papers focus on topics such as driver mutations in noncoding regions of the genome, genetic changes in tumors over time, and molecular processes that cause mutations.
• In Science, researchers reported that T cells edited with CRISPR/Cas9 and reinfused into three patients persisted for up to 9 months. Researchers removed two genes that code for the T-cell receptor so the cells could be reprogrammed to express a synthetic receptor, as well as a third gene that encodes PD-1, to improve antitumor immunity. Although the editing process appears safe, outcomes in patients—two with multiple myeloma and one with sarcoma—were modest.
• On World Cancer Day, two reports were released outlining steps for reducing cancer incidence and mortality in low- and middle-income countries. The reports, published by the World Health Organization and the International Agency for Research on Cancer, recommend interventions such as controlling tobacco use and vaccinating against hepatitis B and human papillomavirus (HPV), and make suggestions for early diagnosis and screening.

• A test for circulating tumor DNA in patients with HPV-linked head and neck cancer could identify cancer recurrence after treatment. Researchers analyzed 1,006 blood samples from 115 patients who were treated for HPV-associated oropharyngeal squamous cell carcinoma, with testing every 6 to 9 months for a median follow-up time of 23 months. The test was 99% accurate at confirming that patients remained cancer-free after treatment, and 94% accurate when detecting recurrence.
• More people are diagnosed with colorectal cancer between ages 49 and 50 than at older ages, according to findings in JAMA Network Open. Researchers performed a year-by-year age analysis on data from 2000 and 2015 and found that the incidence rate was 46.1% higher in this age group than in others. Moreover, 92.9% of cases diagnosed at age 50 were invasive, suggesting that patients may be developing colorectal cancer before the age at which screening is typically recommended.
• Bristol-Myers Squibb announced it will withdraw its application for approval of nivolumab (Opdivo) plus ipilimumab (Yervoy) in advanced non–small cell lung cancer in the European Union. The decision comes after the Committee for Medicinal Products for Human Use determined that it could not fully assess the PD-1–CTLA4 checkpoint inhibitor combination due to protocol changes in the phase III CheckMate-227 trial.
• United Therapeutics’ dinutuximab (Unituxin) plus irinotecan may not be effective in treating relapsed/refractory small cell lung cancer. In the phase II/III DISTINCT trial, the combination did not extend overall survival compared with irinotecan alone. A chimeric monoclonal antibody, dinutuximab is FDA approved for children with high-risk neuroblastoma.

• Lilly announced it will stop developing the PEGylated IL10 pegilodecakin after the drug failed to show a benefit in combination with immunotherapies in two phase II lung cancer trials; previously, the agent failed to improve survival in combination with chemotherapy in a phase III trial of pancreatic cancer. The company acquired the agent when it bought ARMO Biosciences for $1.6 billion in 2018. Eli Lilly will also halt development of galunisertib, a TGFβR1 kinase inhibitor that was in phase II testing to treat solid cancers.
• Cisplatin plus gemcitabine may be effective in patients with pancreatic ductal adenocarcinoma who have BRCA1/2 or PALB2 mutations, researchers reported in the Journal of Clinical Oncology. In a phase II trial, patients who received the combination had a response rate of 74.1%, a median overall survival (OS) of 15.5 months, and a median progression-free survival (PFS) of 10.1 months. Adding veliparib to the combination resulted in a response rate of 65.2%, a median OS of 16.4 months, and median PFS of 9.7 months, and led to more hematologic side effects.
• The FDA will review a combination of encorafenib (Braftovi; Array Biopharma) and cetuximab (Erbitux; Eli Lilly) for metastatic, BRAF-mutant colorectal cancer, rather than a three-drug regimen that also includes binimetinib (Mektovi; Array BioPharma). The decision comes after no difference in median OS or median PFS was found between the doublet and triplet arms in the phase III BEACON CRC trial; both experimental arms led to significantly better outcomes than standard cetuximab plus chemotherapy.

• CT screening for lung cancer significantly decreases mortality from the disease, according to findings published in The New England Journal of Medicine. Researchers randomly assigned former and current smokers to two groups: one that underwent CT screenings at the start of the study and after 1, 3, and 5.5 years, and another that had no screening. They found that after 10 years of follow-up, lung cancer mortality in the screening group was 2.5 deaths per 1,000 person-years, compared with 3.3 deaths per 1,000 person-years in the nonscreening group.
• A paper in Nature reported that tobacco smoking increases mutations in bronchial epithelial cells, but kicking the habit can reverse this mutational process—at least somewhat. Researchers performed whole-genome sequencing on 632 cell colonies created from bronchial epithelial cells from 16 people, and found that tobacco smokers had 1,000 to 10,000 more mutations per cell than nonsmokers. However, former smokers were four times more likely than current smokers to have cells with mutational burdens similar to those seen in cells of nonsmokers—and these cells in former smokers had fewer mutations associated with tobacco use.
• The FDA released six final guidances and one draft guidance on developing gene therapies. The guidances cover a range of topics, including manufacturing concerns and recommendations in specific disease areas, as well as evaluating “sameness” between multiple gene therapies developed for the same disease. “As the regulators of these novel therapies, we know that the framework we construct for product development and review will set the stage for continued advancement of this cutting-edge field,” said Peter Marks, MD, PhD, director of the FDA’s Center for Biologics Evaluation and Research.

• The FDA approved tazemetostat (Tazverik; Epizyme) in patients age 16 and older with inoperable metastatic or locally advanced epithelioid sarcoma. The decision was based on the phase II Study EZH-202 trial, in which the drug elicited an objective response rate of 15%. Tazemetostat is the first EZH2 inhibitor to be approved by the FDA.
• Less than half of clinical trials report results to the FDA within a year of completion, according to findings in The Lancet. Researchers analyzed 4,209 trials and found that only 40.9% reported results within the 1-year timeframe required by the FDA Amendments Act of 2007. Industry sponsors were significantly more likely to report results than non-industry, non–U.S. government sponsors. The median time from trial completion to data submission was 424 days.
• Newer drug combinations may help patients with certain liver and colorectal cancers maintain their quality of life longer than standard treatments, researchers reported at the American Society of Clinical Oncology’s 2020 Gastrointestinal Cancers Symposium in San Francisco, CA, January 23–25. In the phase III IMbrave 150 trial, patients with inoperable hepatocellular carcinoma treated with atezolizumab (Tecentriq; Genentech) plus bevacizumab (Avastin; Genentech) reported a median time to deterioration of 11.2 months, compared with 3.6 months for patients who received standard sorafenib (Nexavar; Bayer). In the phase III BEACON CRC trial, patients with BRAF-mutant colorectal cancer treated with encorafenib (Braftovi; Array BioPharma) and cetuximab (Erbitux; Lilly) with or without binimetinib (Mektovi; Array BioPharma) had a 44% to 46% reduction in the risk of their quality of life deteriorating compared with standard chemotherapy.

• BeiGene announced that tislelizumab plus chemotherapy may be effective in patients with squamous non–small cell lung cancer. In a phase III trial, the combination extended progression-free survival (PFS) compared with chemotherapy alone. A PD-1 inhibitor, tislelizumab is approved in China for relapsed/refractory Hodgkin lymphoma.
• The European Commission (EC) approved polatuzumab vedotin (Polivy; Roche) plus bendamustine and rituximab in patients with relapsed/refractory diffuse large B-cell lymphoma who are not candidates for a stem-cell transplant. A CD79b-directed antibody–drug conjugate, polatuzumab vedotin was approved based on a phase Ib/II trial in which patients treated with the combination had a complete response rate of 40% and a median overall survival of 12.4 months, compared with 17.5% and 4.7 months in patients who received rituximab alone.
• The EC also approved daratumumab (Darzalex; Janssen) plus bortezomib (Velcade; Millennium Pharmaceuticals), thalidomide, and dexamethasone (VTd) in patients with newly diagnosed multiple myeloma who are unable to receive a stem-cell transplant. The decision was based in part on the phase III CASSIOPEIA trial in which patients treated with the daratumumab-based combination had an 18-month PFS rate of 93%, compared with 85% in patients who received VTd alone.
• Boston, MA’s Dana-Farber Cancer Institute will create the Riney Family Multiple Myeloma Initiative after receiving a $16.5 million donation from the family. The initiative will focus on three research areas: understanding the biological drivers of multiple myeloma, developing novel therapeutics, and creating the infrastructure for open-access data and resources.

• Incyte will pay MorphoSys $750 million for tafasitamab in a deal that could be worth another $1.1 billion in milestone payments. An anti-CD19 agent, tafasitamab is being tested in combination with lenalidomide (Revlimid; Bristol-Myers Squibb [BMS]/Celgene) in diffuse large B-cell lymphoma: In the phase II L-MIND trial, the combination elicited a response rate of 60%.
• Astellas inked a $50 million deal with Adaptimmune that could be worth up to $897.5 million more in milestone payments. Under the agreement, the companies will co-develop allogeneic chimeric antigen receptor T-cell and T-cell receptor therapies. Adaptimmune will identify up to three targets, and Astellas will fund research through phase I testing, after which promising candidates will continue to be developed by one or both companies.
• Nektar Therapeutics and BMS announced that they will develop a combination of their drugs—bempegaldesleukin (Nektar) plus nivolumab (Opdivo; BMS). The companies will expand clinical testing of the IL2-pathway agonist–PD-1 inhibitor combination by initiating trials in melanoma, bladder cancer, and renal cell carcinoma.
• A biotech called EQRx was launched at the JP Morgan Chase & Co. Health Care Conference in San Francisco, CA. Focusing on therapies for cancers and genetic diseases, the company aims to develop drugs at a lower cost, possibly trimming prices by up to 66%.
• Two organizations published updated recommendations for endocrine receptor (ER) testing. As in an earlier version, the College of American Pathologists and the American Society of Clinical Oncology recommend ER testing invasive breast cancers by immunohistochemistry; cancers with 1% to 100% ER staining should be considered positive and eligible for endocrine therapy. However, the guidance now recommends that tumors with 1% to 10% ER staining be reported in a new category, ER low positive. Additionally, laboratories should establish protocols to ensure the validity of ER low positive or ER negative results.

• The FDA recommended transitioning to duodenoscopes with disposable parts to facilitate cleaning and reduce the risk of contamination and disease transmission. So far, the agency has approved duodenoscopes made by Fujifilm and Pentax with throwaway endcaps, and a fully disposable device made by Boston Scientific. The devices are used to check for diseases in the pancreas and bile ducts, including pancreatic cancer.
• The UK’s National Institute for Health and Care Excellence (NICE) recommended the CDK4/6 inhibitor palbociclib (Ibrance; Pfizer), in combination with fulvestrant, for patients with hormone receptor–positive, HER2-negative, advanced breast cancer who have received prior endocrine therapy. The agency also recommended the PARP inhibitor olaparib (Lynparza; AstraZeneca) for relapsed, platinum-sensitive BRCA-mutant ovarian, fallopian tube, or peritoneal cancer. Based on the recommendations, both agents will be made available by the National Health Service England through its Cancer Drugs Fund.
• NICE did not recommend the PD-L1 inhibitor pembrolizumab (Keytruda; Merck) in patients with newly diagnosed metastatic or inoperable recurrent head and neck squamous cell carcinoma due to concerns that the trial design did not reflect treatment protocols. The agency also recommended against the FLT3 inhibitor gilteritinib (Xospata; Astellas) in relapsed/refractory FLT3-positive acute myeloid leukemia, citing a lack of long-term survival data that met its requirements for cost effectiveness. The lack of support means that the drugs will not be made available by the National Health Service England.

• The FDA approved avapritinib (Ayvakit; Blueprint Medicines) for patients with inoperable or metastatic gastrointestinal stromal tumors who have PDGFRA exon 18 alterations, including PDGFRA D842V mutations. The approval was based on the phase I NAVIGATOR trial in which patients with PDGFRA exon 18 mutations had an overall response rate (ORR) of 84%, and those with PDGFRA D842V mutations had an ORR of 89%. Avapritinib inhibits mutant KIT and PDGFRA kinases.
• The agency also approved pembrolizumab (Keytruda; Merck) for certain patients with high-risk, non–muscle-invasive bladder cancer. The approval was based on the phase II KEYNOTE-057 trial in which patients treated with the PD-1 inhibitor had a complete response rate of 41% and a median duration of response of 16.2 months.
• The American Cancer Society reported that the cancer mortality rate in the United States dropped by 2.2% between 2016 and 2017, the largest-ever single-year decline. Overall, the cancer death rate has declined by 29% since 1991—driven largely by improved survival for patients with lung, colorectal, breast, and prostate cancers—saving 2.9 million lives. The report predicted that there will be 1.8 million new cancer cases and 606,520 cancer deaths in the United States in 2020.

• Merck announced a $50 million deal with Taiho and Astex that could be worth up to $2.5 billion in milestone payments. Under the arrangement, Merck will gain access to preclinical drug candidates in development by Taiho and Astex, including small-molecule inhibitors that target KRAS.
• EMD Serono/Pfizer’s PD-1 inhibitor avelumab (Bavencio) may be an effective maintenance therapy in patients with locally advanced or metastatic urothelial carcinoma whose disease did not worsen on induction chemotherapy. In the phase III JAVELIN Bladder 100 trial, the therapy plus best supportive care significantly improved overall survival compared with best supportive care alone.
• According to a data brief released by the National Center for Health Statistics, an increasing number of U.S. adults are receiving the human papillomavirus vaccine. Between 2013 to 2018, the percentage of adults ages 18 to 26 who received at least one dose of the vaccine climbed from 22.1% to 39.9%, and the percentage who received the recommended number of doses rose from 13.8% to 21.5%.