Standard therapy for advanced gastric cancer that progresses on first-line therapy with a platinum and a fluoropyrimidine includes paclitaxel. The anti-PD-1 antibody pembrolizumab (pembro), which prevents PD-1 from binding to its ligands PD-L1 and PD-L2, has shown an acceptable safety profile and clinical activity in patients (pts) with advanced malignancies. In KEYNOTE-012, pembro 10 mg/kg Q2W showed a manageable safety profile and 22% ORR in pts with advanced gastric cancer. The randomized, open-label, phase 3 KEYNOTE-061 study (NCT02370498) is designed to compare the efficacy and safety of pembro with those of paclitaxel in the second-line treatment of advanced gastric cancer.
Key eligibility criteria are metastatic or unresectable gastric or GEJ adenocarcinoma that progressed after first-line platinum + fluoropyrimidine chemotherapy (with trastuzumab for pts with HER2/neu+ tumors, measurable disease per RECIST v1.1, ECOG PS 0-1, no chemotherapy within 2 wk of first dose of study drug, and provision of a newly obtained or archival tumor sample for assessing PD-L1 status. Eligible pts will be randomized 1:1 to receive pembro 200 mg Q3W or paclitaxel 80 mg/m2 IV on days 1, 8, and 15 of each 28-d cycle. Treatment will continue until progression, intolerable toxicity, or pt or investigator decision. In the pembro arm, pts who have a CR after ≥24 wk may discontinue after ≥2 doses following initial CR; maximum duration of pembro is 24 mo. Clinically stable pts who progress per RECIST v1.1 may continue pembro at the discretion of the investigator until a confirmatory scan performed ≥4 wk later. Response will be assessed every 6 wk for the first 6 mo and every 12 wk thereafter per RECIST v1.1 by central review and per RECIST adapted for the unique response patterns that may be observed with immunotherapy. AEs will be assessed throughout treatment and for 30 d thereafter (up to 90 d for serious AEs). Primary efficacy end points are PFS and OS in pts with PD-L1+ tumors. Secondary end points include PFS and OS in all pts, time to progression, ORR, and duration of response. KEYNOTE-061 enrollment is ongoing and will continue until as many as 720 pts are enrolled.
Clinical trial identification
J. Tabernero: consultant/advisor for Amgen, Imclone, Lilly, Merck Serono, Merck & Co., Inc., Millennium, Novartis, Roche, Sanofi, Celgene, Chugai and Taiho. L. Sun, Z. Wang: employee of Merck & Co., Inc. I. Csiki: currently employed at Merck & Co., Inc.; previously employed at GlaxoSmithKline; owns stock in Merck & Co., Inc. and GlaxoSmithKline. M. Koshiji: currently employed at Merck & Co., Inc.; previously employed at Lilly; owns stock in Lilly. E. Van Cutsem: consultant/advisor for Merck & Co., Inc. All other authors have declared no conflicts of interest.