NCI10066: a Phase 1/2 study of olaparib in combination with ramucirumab in previously treated metastatic gastric and gastroesophageal junction adenocarcinoma.

"data availability the genomic data for the broca-hr panel are publicly available in sequence read archive bioproject id prjna1037163. data availability the genomic data for the broca-hr panel are publicly available in sequence read archive bioproject id prjna1037163"

"Competing interests Dr. Michael Cecchini reports consulting fees from Eisai Inc., Agios Pharmaceuticals, AstraZeneca, Daiichi Sankyo, Macrogenics, Seattle Genetics, DAVA Oncology, Bayer Pharmaceuticals, Regeneron, and Parthenon Therapeutics. Dr. JMC receives research funding to his institution from Merus, Roche, Servier, and Bristol-Myers Squibb. He receives research support from Merck, AstraZeneca, Esperas Pharma, Bayer, Tesaro, Arcus Biosciences, and Apexigen; he has also received honoraria for being on the advisory boards of Incyte and Blueprint Medicines. Dr. EMS reports consulting fees from Ideaya Biosciences and DSMB for Novartis and research support to institution from GSK. May Cho reports honoraria from presentations and advisory boards and travel support from AstraZeneca. EK reports advisory board support from Eli Lilly and Relay Therapeutics, honoraria from presentations from Eisai Inc and Seattle Genetics, consulting fees from Eisai Inc, Taiho, Eli Lilly, and Relay Therapeutics as well as stock from ROMTech. EK also reports institutional grants or contracts from NGM Biopharmaceuticals, Erytech, Fibrogen, Eureka, Merck, Bristol-Myers Squibb, Astellas, Boston Biomedical, AstraZeneca, Celgene, Halozyme, Sanumed, Epicentryx, and Medimmune. LG reports consulting or advisory roles from QED Therapeutics, Genentech, Merck, AstraZeneca, Exelixis, Boehringer Ingelheim, Cardinal Health, Athenum Consulting and Relay Therapeutics. LG also reports research funding from Bristol-Myers Squibb, Agios, ASLAN Pharmaceuticals, Beigene, Basilea, and Merck. JC reports grants or contracts to institution from Merck and Brooklyn Immunotherapeutics, and consulting fees to himself from Eli Lilly, Merck, AstraZeneca, Foundation Medicine, Daiichi Sankyo, Amgen, Bristol-Myers Squibb, Astellas, Turning Point Therapeutics, Silverback Therapeutics, Novartis, Coherus Biosciences, Geneos, Roche, and Guardant Health. JC also reports payments or honoraria for presentations from Merck and Bristol-Myers Squibb, Data Safety Monitoring Board participation from Yiviva and Daiichi Sankyo, and stock or stock options from Amgen as well as current employment by Amgen."

"Funding The clinical trial was funded through the National Cancer Institute UM1 grant (1UM1CA186689) of which P LoRusso is the principal investigator. The genomic analysis was partially funded by an American Society of Clinical Oncology Young Investigator Award for Michael Cecchini. M Cecchini is supported by a National Cancer Institute Mentored Clinical Scientist Research Career Development Award (1K08CA255465)."

"NCI10066 was a single-arm open-label Phase 1/2 clinical trial open through the National Cancer Institute (NCI) ETCTN. Eligible patients had stage IV, histopathologically confirmed gastric or GEJ adenocarcinoma that had progressed after at least one standard therapy in the metastatic setting. The study consisted of a dose escalation portion followed by dose expansion. The dose escalation proceeded with a standard 3 + 3 design with a dose-limiting toxicity evaluation period for 28 days from treatment initiation. In dose expansion, enrolment proceeded at the RP2D. Eligible patients were 18 years of age or older, had measurable disease according to Response Evaluation Criteria in Solid Tumours (RECIST, version 1.1), had an Eastern Cooperative Oncology Group (ECOG) performance score of 0 or 1, and had adequate organ function (as assessed by renal, hepatic, and haematologic parameters). Patients were excluded if they had previously received ramucirumab. The NCI Cancer Therapy Evaluation Program and the NCI Central Institutional Review Board approved the protocol and all patients provided written informed consent. The full study protocol is available in the supplementary data. The study was conducted in accordance with the Declaration of Helsinki and followed the Consolidated Standards of Reporting Trials. Trial registration: ClinicalTrials.gov identifier: (NCT03008278)."