Table 2.

Monotherapy and combination trials involving DDR inhibitors that have completed or are currently recruiting (www.clinicaltrials.gov)

TargetAgentPhaseInterventionCancer(s) enrolledStatus/resultsTrial identifierRef.
DNA-PKMSC2490484AIMSC2490484ASolid tumors, CLLRecruitingNCT02316197
MSC2490484AIMSC2490484A ± RTSolid tumorsRecruitingNCT02516813
VX-984IVX-984 ± PLDSolid tumorsRecruitingNCT02644278
CC-115aICC-115GBM, HNSCC, prostate, ES, CLL37% (3/8) PR in relapsed ATM-mutant CLLNCT01353625(45, 46)
ATMAZD0156IAZD0156 ± olaparibSolid tumorsRecruitingNCT02588105
ATRVX-970 ± chemotherapyIVX-970 ± carboplatinSolid tumorsRecruitingEudraCT: 2013-005100-34(67, 68)
IVX-970 ± gemcitabine, etoposide, cisplatin or carboplatinSolid tumorsRecruitingNCT02157792(69, 70)
IIGemcitabine ± VX-970 (randomized)Ovarian, primary peritoneal or Fallopian tubeRecruitingNCT02595892
IVX-970 + irinotecanSolid tumorsRecruitingNCT02595931
IICarboplatin + gemcitabine ± VX-970 (randomized)Advanced gynecologic cancersNot yet recruitingNCT02627443
I/IIVX-970 + topotecanAdvanced NSCLC, SCLC, Gynae or neuroendocrineRecruitingNCT02487095
IICisplatin + gemcitabine ± VX-970 (randomized)Advanced urothelialRecruitingNCT02567409
VX-970 ± RTICisplatin + RT ± VX-970Locally advanced HNSCCRecruitingNCT02567422
IWhole brain RT + VX-970NSCLC brain metastasesRecruitingNCT02589522
VX-970 + targeted therapyIVX-970 + veliparib + cisplatinSolid tumorsRecruitingNCT02723864
AZD6738IAZD6738Relapsed CLL, PLL, B-cell lymphomasComplete, full results awaitedNCT01955668
AZD6738 ± chemotherapyIAZD6738 ± carboplatin, olaparib or MEDI4736Solid tumors, HNSCC, ATMloss NSCLC, gastric or GOJ carcinomaRecruitingNCT02264678
IAZD6738 + paclitaxelSolid tumorsRecruitingNCT02630199
AZD6738 + RTIAZD6738 + palliative RTSolid tumorsRecruitingNCT02223923
CHK1MK8776 (SCH 900776)IICytarabine ± MK8776 (randomized)Relapsed AMLComplete, full results awaitedNCT01870596
IGemcitabine + MK8776Relapsed lymphomaComplete, full results awaitedNCT00779584(72)
ICytarabine + MK8776Relapsed AML33% (8/24) CRNCT00907517(158)
LY2603618I/IICisplatin/pemetrexed ± LY2603618NSCLC14% (2/14) PRNCT01139775(159)
I/IIGemcitabine ± LY2603618Pancreatic carcinomaComplete, full results awaitedNCT00839332
IIPemetrexed + LY2603618NSCLCComplete, full results awaitedNCT00988858
ILY2603618 + pemetrexed or gemcitabineSolid tumorsComplete, full results awaitedNCT01296568
ILY2603618 + gemcitabineSolid tumorsComplete, full results awaitedNCT01341457(73)
ILY2603618 + pemetrexedSolid tumorsComplete, full results awaitedNCT00415636
CCT245737ICCT245737Solid tumorsRecruitingNCT02797964
ICCT245737 + cisplatin and/or gemcitabineSolid tumorsRecruitingNCT02797977
GDC-0575 ± chemotherapyIGDC-0575 ± gemcitabineSolid tumors, relapsed lymphomaComplete, full results awaitedNCT01564251
CHK1/2LY2606368IILY2606368Refractory SCLCRecruitingNCT02735980
IILY2606368Ovarian, breast, prostateRecruitingNCT02203513
IILY2606368Solid tumorsRecruitingNCT02873975
ILY2606368Solid tumors4% (2/45) PR—anal SCC, HNSCCNCT01115790(76)
ILY2606368Solid tumorsRecruitingNCT02778126
ILY2606368Solid tumorsRecruitingNCT02514603
ILY2606368Pediatric solid tumorsRecruitingNCT02808650
LY2606368 + chemotherapyILY2606368 + fludarabine + cytarabineRelapsed AML, high risk MDSRecruitingNCT02649764
ILY2606368 + cisplatin, cetuximab, pemetrexed, fluorouracil and/or leucovorinSolid tumorsRecruitingNCT02124148
LY2606368 + targeted therapyILY2606368 + ralimetinib (MAPK inhibitor)Solid tumorsRecruitingNCT02860780
LY2606368 + RTILY2606368 + RT + cisplatin or cetuximabLocally advanced HNSCCRecruitingNCT02555644
WEE1AZD1775IIAZD1775SCLCRecruitingNCT02593019
IAZD1775Solid tumors8% (2/25) PR: BRCA-mutant ovarian, BRCA-mutant HNSCCNCT01748825(82)
IAZD1775Solid tumorsRecruitingNCT02482311(160)
IAZD1775Solid tumorsRecruitingNCT02610075
AZD1775 + chemotherapyIICarboplatin/paclitaxel ± AZD1775Ovarian, TP53mutComplete, full results awaitedNCT01357161(85)
IICarboplatin + AZD1775Ovarian, TP53mut, or platinum resistant
  • ORR 9/21 (43%), with prolonged CR in 1/21 (5%).

  • Median PFS: 5.3 months. Median OS: 12.6 months; two patients with ongoing response for more than 31 and 42 months at data cutoff

NCT01164995(84)
IIGemcitabine ± AZD1775Ovarian, primary peritoneal, or fallopianRecruitingNCT02101775
IICarboplatin/pemetrexed ± AZD1775NSCLC, 1st lineComplete, full results awaitedNCT02087241
IIDocetaxel + AZD1775NSCLC, 2nd lineClosedNCT02087176
IICarboplatin/paclitaxel + AZD1775NSCLCRecruitingNCT02513563
IIPaclitaxel weekly + AZD1775Gastric carcinomaRecruitingNCT02448329
IICisplatin ± AZD1775HNSCCComplete, full results awaitedNCT02196168
I/IIGemcitabine/nab-paclitaxel ± AZD1775PancreaticRecruitingNCT02194829
I/IIIrinotecan + AZD1775Pediatric solid tumorsRecruitingNCT02095132
ICisplatin/docetaxel + AZD1775Locally advanced HNSCCRecruitingNCT02508246
IGemcitabine, cisplatin or carboplatin + AZD1775Solid tumorsPR in 17/176 (10%). RR higher in TP53-mutated vs. wild-type patients: 21% (n = 19) vs. 12% (n = 33)NCT00648648(83)
AZD1775 + targeted therapyIAZD1775 + olaparib (PARP inhibitor)Solid tumorsComplete, full results awaitedNCT02511795(161)
AZD1775 + Belinostat (HDAC inhibitor)AML, other myeloid malignanciesRecruitingNCT02381548
AZD1775 + RTI/IIRadiation + gemcitabine + AZD1775PancreaticRecruitingNCT02037230
IRadiation + cisplatin + AZD1775HNSCCRecruitingNCT02585973(162)
IRT + cisplatin + AZD1775Locally advanced cervical cancerRecruitingNCT01958658
IRadiation + temozolomide + AZD1775GBMRecruitingNCT01849146
IRadiation + AZD1775Pediatric DIPGRecruitingNCT01922076
AZD1775 + immune checkpoint inhibitorIMEDI4736 + AD1775Solid tumorsRecruitingNCT02617277
BERTRC102ITRC102Solid tumors, lymphomaComplete, full results awaitedNCT01851369(90)
TRC102 + chemotherapyIITRC102 + temozolomideGBMRecruitingNCT02395692
I/IITRC102 + cisplatin and/or pemetrexedSolid tumorsRecruitingNCT02535312
ITRC102 + pemetrexedSolid tumors4% (1/28) PR: HNSCCNCT00692159(89)
ITRC102 + fludarabineHematologic malignanciesComplete, full results awaitedNCT01658319
TRC102 + RTITRC + RT + cisplatin ± pemetrexedNSCLCRecruitingNCT02535325
  • Abbreviations: AML, acute myeloid leukemia; CLL, chronic lymphocytic leukemia; CR, complete response; CRUK, Cancer Research UK; DIPG, diffuse intrinsic pontine gliomas; ES, Ewing sarcoma; GBM, glioblastoma multiforme; GOJ, gastro-oesphageal carcinoma; HDAC, histone deacetylase; HGSOC, high-grade serous ovarian carcinoma; HNSCC, head and neck squamous cell carcinoma; mAb, monoclonal antibody; MDS, myelodysplastic syndrome; NCI, National Cancer Institute; NSCLC, non–small cell lung carcinoma; ORR, objective response rate; PFS, progression-free survival; PLD, pegylated liposomal doxorubicin; PLL, prolymphocytic leukemia; PR, partial response; RT, radiotherapy; SCLC, small cell lung carcinoma.

  • aDual DNA-PK and mTOR inhibitor.