197TiP - A randomized, double-blind, phase III study of pembrolizumab plus chemotherapy as first-line therapy in patients with HER2-negative, advanced gastric or gastroesophageal junction (G/GEJ) adenocarcinoma: KEYNOTE-859

Background

For patients with HER2–negative recurrent or metastatic G/GEJ cancer, standard first-line therapy includes a fluoropyrimidine + a platinum-based agent. Accumulating evidence has shown that PD-1 inhibitor pembrolizumab + chemotherapy can improve clinical outcomes in this population. The phase III KEYNOTE-859 trial (NCT03675737) is investigating first-line pembrolizumab + chemotherapy in patients with advanced G/GEJ cancer.

Trial design

Eligible patients are ≥18 years old with previously untreated HER2–negative advanced G/GEJ adenocarcinoma, measurable disease per RECIST v1.1, adequate tumor tissue sample for PD-L1 biomarker analysis, and ECOG performance status 0 or 1. Patients will be randomly assigned 1:1 to pembrolizumab 200 mg or placebo intravenously (IV) every 3 weeks (Q3W) in combination with the investigator’s choice of FP (continuous infusion of 5-fluorouracil [800 mg/m²/day on days 1-5 of each cycle] + IV cisplatin [80 mg/m²] Q3W) or CAPOX (oral capecitabine [1000 mg/m² twice daily on days 1-14 of each cycle] + IV oxaliplatin [130 mg/m² on day 1 of each cycle] Q3W). Duration of cisplatin or oxaliplatin may be capped at 6 cycles per local country guidelines; treatment with 5-fluorouracil or capecitabine may continue per protocol. Treatment with pembrolizumab/placebo will continue for up to 35 administrations (∼2 years) or until disease progression, unacceptable toxicity, intercurrent illness that prevents further administration of treatment, or noncompliance. Patients will be stratified by geographic region (Europe/Israel/North America/Australia vs Asia vs rest of world), PD-L1 tumor expression status (combined positive score <1 vs ≥1), and combination chemotherapy (FP vs CAPOX). Imaging will be performed Q6W, and adverse events (AEs) will be monitored throughout the study and for 30 days after treatment (90 days for serious AEs). The dual primary end points are OS and PFS per RECIST v1.1 as assessed by blinded independent central review (BICR). Secondary end points include ORR and DOR per RECIST v1.1 as assessed by BICR and safety. Enrollment is ongoing.

Clinical trial identification

NCT03675737.

Legal entity responsible for the study

Merck Sharp and Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA.

Funding

Funding for this study was provided by Merck Sharp and Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA.

Disclosure

J. Tabernero: Advisory/Consultancy: Array Biopharma, AstraZeneca, Bayer, BeiGene, Boehringer Ingelheim, Chugai, Genentech, Inc., Genmab A/S, Halozyme, Imugene Limited, Inflection Biosciences Limited, Ipsen, Kura Oncology, Lilly, MSD, Menarini, Merck Serono, Merrimack, Merus, Molecular Part. E. van Cutsem: Advisory/Consultancy: Bayer, Lilly, Roche, Servier, BMS, Celegene, MSD, Merck KGaA, Novartis, AstraZeneca, Halozyme, Array BioPharma; Research grant/Funding (institution): Amgen, Bayer, Boehringer Ingelheim, Lilly, Novartis, Roche, Celegene, Ipsen, Merck, Merck KGaA, Servier, BMS. C.S. Fuchs: Advisory/Consultancy: Agios, Amylin Pharmaceuticals, Bain Capital, CytomX Therapeutics, Daiichi-Sankyo, Eli Lilly, Entrinsic Health, Evolveimmune Therapeutics, Genentech, Merck, Taiho, Unum Therapeutics; Leadership role: CytomX Therapeutics (director), Evolveimmune Therapeutics (co-founder); Shareholder/Stockholder/Stock options: CytomX Therapeutics and Entrinsic Health excised options; Evolveimmune Therapeutics. Y.Y. Janjigian: Advisory/Consultancy: Lilly, Pfizer, Merck, Bristol-Myers Squibb, Merck Serono; Research grant/Funding (self): Boehringer Ingelheim, Bayer, Lilly, Amgen, Roche, Genentech. P. Bhagia: Full/Part-time employment: Merck & Co., Inc. K. Li: Full/Part-time employment: Merck & Co., Inc. D. Adelberg: Full/Part-time employment: Merck & Co., Inc. Y-J. Bang: Advisory/Consultancy: AstraZeneca, Novartis, Genentech/Roche, MSD, Merck Serano, Bayer, BMS, Eli Lilly, Taiho, Daiich-Sankyo, Astellas, BeiGene, GreenCross, Samyang Biopharm, Hanmi, Genexine; Research grant/Funding (institution): AstraZeneca, Novartis, Genentech/Roche, MSD, Merck Serano, Bayer, BMS, GSK, Pfizer, Eli Lilly, Boeringer-Ingelheim, MacroGenics, Boston Biomedical, FivePrime, Curis, Taiho, Takeda, Ono, Daiichi Sankyo, Astellas, BeiGene, Green Cross, CKD Pharma, Genexi. All other authors have declared no conflicts of interest.