Skip to main content
  • AACR Publications
    • Blood Cancer Discovery
    • Cancer Discovery
    • Cancer Epidemiology, Biomarkers & Prevention
    • Cancer Immunology Research
    • Cancer Prevention Research
    • Cancer Research
    • Clinical Cancer Research
    • Molecular Cancer Research
    • Molecular Cancer Therapeutics

AACR logo

  • Register
  • Log in
  • My Cart
Advertisement

Main menu

  • Home
  • About
    • The Journal
    • AACR Journals
    • Journal Sections
    • Subscriptions
    • Reviewing
    • Permissions and Reprints
  • Articles
    • OnlineFirst
    • Current Issue
    • Past Issues
    • Collections
      • COVID-19 & Cancer Resource Center
      • Clinical Trials
      • Immuno-oncology
      • Editors' Picks
      • "Best of" Collection
  • For Authors
    • Information for Authors
    • Author Services
    • Best of: Author Profiles
    • Submit
  • Alerts
    • Table of Contents
    • Editors' Picks
    • OnlineFirst
    • Citation
    • Author/Keyword
    • RSS Feeds
    • My Alert Summary & Preferences
  • News
    • Cancer Discovery News
    • Journal Press Releases
  • COVID-19
  • Webinars
  • 10th Anniversary
  • Search More

    Advanced Search

  • AACR Publications
    • Blood Cancer Discovery
    • Cancer Discovery
    • Cancer Epidemiology, Biomarkers & Prevention
    • Cancer Immunology Research
    • Cancer Prevention Research
    • Cancer Research
    • Clinical Cancer Research
    • Molecular Cancer Research
    • Molecular Cancer Therapeutics

User menu

  • Register
  • Log in
  • My Cart

Search

  • Advanced search
Cancer Discovery
Cancer Discovery
  • Home
  • About
    • The Journal
    • AACR Journals
    • Journal Sections
    • Subscriptions
    • Reviewing
    • Permissions and Reprints
  • Articles
    • OnlineFirst
    • Current Issue
    • Past Issues
    • Collections
      • COVID-19 & Cancer Resource Center
      • Clinical Trials
      • Immuno-oncology
      • Editors' Picks
      • "Best of" Collection
  • For Authors
    • Information for Authors
    • Author Services
    • Best of: Author Profiles
    • Submit
  • Alerts
    • Table of Contents
    • Editors' Picks
    • OnlineFirst
    • Citation
    • Author/Keyword
    • RSS Feeds
    • My Alert Summary & Preferences
  • News
    • Cancer Discovery News
    • Journal Press Releases
  • COVID-19
  • Webinars
  • 10th Anniversary
  • Search More

    Advanced Search

Research Articles

Safety and Antitumor Activity of the Multitargeted Pan-TRK, ROS1, and ALK Inhibitor Entrectinib: Combined Results from Two Phase I Trials (ALKA-372-001 and STARTRK-1)

Alexander Drilon, Salvatore Siena, Sai-Hong Ignatius Ou, Manish Patel, Myung Ju Ahn, Jeeyun Lee, Todd M. Bauer, Anna F. Farago, Jennifer J. Wheler, Stephen V. Liu, Robert Doebele, Laura Giannetta, Giulio Cerea, Giovanna Marrapese, Michele Schirru, Alessio Amatu, Katia Bencardino, Laura Palmeri, Andrea Sartore-Bianchi, Angelo Vanzulli, Sara Cresta, Silvia Damian, Matteo Duca, Elena Ardini, Gang Li, Jason Christiansen, Karey Kowalski, Ann D. Johnson, Rupal Patel, David Luo, Edna Chow-Maneval, Zachary Hornby, Pratik S. Multani, Alice T. Shaw and Filippo G. De Braud
Alexander Drilon
1Memorial Sloan Kettering Cancer Center and Weill Cornell Medical College, New York, New York.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • For correspondence: drilona@mskcc.org
Salvatore Siena
2Niguarda Cancer Center, Grande Ospedale Metropolitano Niguarda, Milan, Italy.
3Dipartimento di Oncologia e Emato-Oncologia, Università degli Studi di Milano, Milan, Italy.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Sai-Hong Ignatius Ou
4Chao Family Comprehensive Cancer Center, University of California, Irvine, California.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Manish Patel
5Sarah Cannon Research Institute/Florida Cancer Specialists, Sarasota, Florida.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Myung Ju Ahn
6Samsung Medical Center, Seoul, Korea.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Jeeyun Lee
6Samsung Medical Center, Seoul, Korea.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Todd M. Bauer
7Sarah Cannon Research Institute/Tennessee Oncology, PLLC, Nashville, Tennessee.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Anna F. Farago
8Massachusetts General Hospital, Boston, Massachusetts.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Jennifer J. Wheler
9The University of Texas MD Anderson Cancer Center, Houston, Texas.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Stephen V. Liu
10Georgetown Lombardi Comprehensive Cancer Center, Washington, DC.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Robert Doebele
11University of Colorado Cancer Center, Aurora, Colorado.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Laura Giannetta
2Niguarda Cancer Center, Grande Ospedale Metropolitano Niguarda, Milan, Italy.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Giulio Cerea
2Niguarda Cancer Center, Grande Ospedale Metropolitano Niguarda, Milan, Italy.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Giovanna Marrapese
2Niguarda Cancer Center, Grande Ospedale Metropolitano Niguarda, Milan, Italy.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Michele Schirru
2Niguarda Cancer Center, Grande Ospedale Metropolitano Niguarda, Milan, Italy.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Alessio Amatu
2Niguarda Cancer Center, Grande Ospedale Metropolitano Niguarda, Milan, Italy.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Katia Bencardino
2Niguarda Cancer Center, Grande Ospedale Metropolitano Niguarda, Milan, Italy.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Laura Palmeri
2Niguarda Cancer Center, Grande Ospedale Metropolitano Niguarda, Milan, Italy.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Andrea Sartore-Bianchi
2Niguarda Cancer Center, Grande Ospedale Metropolitano Niguarda, Milan, Italy.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Angelo Vanzulli
2Niguarda Cancer Center, Grande Ospedale Metropolitano Niguarda, Milan, Italy.
3Dipartimento di Oncologia e Emato-Oncologia, Università degli Studi di Milano, Milan, Italy.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Sara Cresta
12Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Silvia Damian
12Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Matteo Duca
12Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Elena Ardini
13Nerviano Medical Sciences s.r.l, Milan, Italy.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Gang Li
14Ignyta, Inc., San Diego, California.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Jason Christiansen
14Ignyta, Inc., San Diego, California.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Karey Kowalski
14Ignyta, Inc., San Diego, California.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Ann D. Johnson
14Ignyta, Inc., San Diego, California.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Rupal Patel
14Ignyta, Inc., San Diego, California.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
David Luo
14Ignyta, Inc., San Diego, California.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Edna Chow-Maneval
14Ignyta, Inc., San Diego, California.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Zachary Hornby
14Ignyta, Inc., San Diego, California.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Pratik S. Multani
14Ignyta, Inc., San Diego, California.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Alice T. Shaw
8Massachusetts General Hospital, Boston, Massachusetts.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Filippo G. De Braud
3Dipartimento di Oncologia e Emato-Oncologia, Università degli Studi di Milano, Milan, Italy.
12Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
DOI: 10.1158/2159-8290.CD-16-1237 Published April 2017
  • Article
  • Figures & Data
  • Info & Metrics
  • PDF
Loading

Abstract

Entrectinib, a potent oral inhibitor of the tyrosine kinases TRKA/B/C, ROS1, and ALK, was evaluated in two phase I studies in patients with advanced or metastatic solid tumors, including patients with active central nervous system (CNS) disease. Here, we summarize the overall safety and report the antitumor activity of entrectinib in a cohort of patients with tumors harboring NTRK1/2/3, ROS1, or ALK gene fusions, naïve to prior TKI treatment targeting the specific gene, and who were treated at doses that achieved therapeutic exposures consistent with the recommended phase II dose. Entrectinib was well tolerated, with predominantly Grades 1/2 adverse events that were reversible with dose modification. Responses were observed in non–small cell lung cancer, colorectal cancer, mammary analogue secretory carcinoma, melanoma, and renal cell carcinoma, as early as 4 weeks after starting treatment and lasting as long as >2 years. Notably, a complete CNS response was achieved in a patient with SQSTM1–NTRK1-rearranged lung cancer.

Significance: Gene fusions of NTRK1/2/3, ROS1, and ALK (encoding TRKA/B/C, ROS1, and ALK, respectively) lead to constitutive activation of oncogenic pathways. Entrectinib was shown to be well tolerated and active against those gene fusions in solid tumors, including in patients with primary or secondary CNS disease. Cancer Discov; 7(4); 400–9. ©2017 AACR.

This article is highlighted in the In This Issue feature, p. 339

Footnotes

  • Note: Supplementary data for this article are available at Cancer Discovery Online (http://cancerdiscovery.aacrjournals.org/).

  • S. Siena, L. Giannetta, G. Cerea, G. Marrapese, M. Schirru, A. Amatu, K. Bencardino, L. Palmeri, A. Sartore-Bianchi, A. Vanzulli, S. Cresta, S. Damian, M. Duca, and F.G. De Braud are ALKA-372-001 investigators.

  • A. Drilon, S.-H.I. Ou, M. Patel, M.J. Ahn, J. Lee, T.M. Bauer, A.F. Farago, J.J. Wheler, S.V. Liu, R. Doebele, and A.T. Shaw are STARTRK-1 investigators.

  • Received November 3, 2016.
  • Revision received January 24, 2017.
  • Accepted January 25, 2017.
  • ©2017 American Association for Cancer Research.
View Full Text
PreviousNext
Back to top
Cancer Discovery: 7 (4)
April 2017
Volume 7, Issue 4
  • Table of Contents
  • Table of Contents (PDF)
  • About the Cover
  • Editorial Board (PDF)

Sign up for alerts

View this article with LENS

Open full page PDF
Article Alerts
Sign In to Email Alerts with your Email Address
Email Article

Thank you for sharing this Cancer Discovery article.

NOTE: We request your email address only to inform the recipient that it was you who recommended this article, and that it is not junk mail. We do not retain these email addresses.

Enter multiple addresses on separate lines or separate them with commas.
Safety and Antitumor Activity of the Multitargeted Pan-TRK, ROS1, and ALK Inhibitor Entrectinib: Combined Results from Two Phase I Trials (ALKA-372-001 and STARTRK-1)
(Your Name) has forwarded a page to you from Cancer Discovery
(Your Name) thought you would be interested in this article in Cancer Discovery.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Citation Tools
Safety and Antitumor Activity of the Multitargeted Pan-TRK, ROS1, and ALK Inhibitor Entrectinib: Combined Results from Two Phase I Trials (ALKA-372-001 and STARTRK-1)
Alexander Drilon, Salvatore Siena, Sai-Hong Ignatius Ou, Manish Patel, Myung Ju Ahn, Jeeyun Lee, Todd M. Bauer, Anna F. Farago, Jennifer J. Wheler, Stephen V. Liu, Robert Doebele, Laura Giannetta, Giulio Cerea, Giovanna Marrapese, Michele Schirru, Alessio Amatu, Katia Bencardino, Laura Palmeri, Andrea Sartore-Bianchi, Angelo Vanzulli, Sara Cresta, Silvia Damian, Matteo Duca, Elena Ardini, Gang Li, Jason Christiansen, Karey Kowalski, Ann D. Johnson, Rupal Patel, David Luo, Edna Chow-Maneval, Zachary Hornby, Pratik S. Multani, Alice T. Shaw and Filippo G. De Braud
Cancer Discov April 1 2017 (7) (4) 400-409; DOI: 10.1158/2159-8290.CD-16-1237

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
Share
Safety and Antitumor Activity of the Multitargeted Pan-TRK, ROS1, and ALK Inhibitor Entrectinib: Combined Results from Two Phase I Trials (ALKA-372-001 and STARTRK-1)
Alexander Drilon, Salvatore Siena, Sai-Hong Ignatius Ou, Manish Patel, Myung Ju Ahn, Jeeyun Lee, Todd M. Bauer, Anna F. Farago, Jennifer J. Wheler, Stephen V. Liu, Robert Doebele, Laura Giannetta, Giulio Cerea, Giovanna Marrapese, Michele Schirru, Alessio Amatu, Katia Bencardino, Laura Palmeri, Andrea Sartore-Bianchi, Angelo Vanzulli, Sara Cresta, Silvia Damian, Matteo Duca, Elena Ardini, Gang Li, Jason Christiansen, Karey Kowalski, Ann D. Johnson, Rupal Patel, David Luo, Edna Chow-Maneval, Zachary Hornby, Pratik S. Multani, Alice T. Shaw and Filippo G. De Braud
Cancer Discov April 1 2017 (7) (4) 400-409; DOI: 10.1158/2159-8290.CD-16-1237
del.icio.us logo Digg logo Reddit logo Twitter logo CiteULike logo Facebook logo Google logo Mendeley logo
  • Tweet Widget
  • Facebook Like
  • Google Plus One

Jump to section

  • Article
    • Abstract
    • Introduction
    • Results
    • Discussion
    • Methods
    • Disclosure of Potential Conflicts of Interest
    • Authors' Contributions
    • Grant Support
    • Footnotes
    • References
  • Figures & Data
  • Info & Metrics
  • PDF
Advertisement

Related Articles

Cited By...

More in this TOC Section

  • Genetically Defined High-Grade Serous Ovarian Cancer Models
  • Personalized Antibodies for Gastroesophageal Adenocarcinoma
  • Fibroblastic NetG1 Promotes Pancreatic Cancer
Show more Research Articles
  • Home
  • Alerts
  • Feedback
  • Privacy Policy
Facebook   Twitter   LinkedIn   YouTube   RSS

Articles

  • OnlineFirst
  • Current Issue
  • Past Issues

Info For

  • Authors
  • Subscribers
  • Advertisers
  • Librarians

About Cancer Discovery

  • About the Journal
  • Editors
  • Journal Sections
  • Permissions
  • Submit a Manuscript
AACR logo

Copyright © 2021 by the American Association for Cancer Research.

Cancer Discovery
eISSN: 2159-8290
ISSN: 2159-8274

Advertisement