Phase III KEYNOTE-585 study of chemotherapy (Chemo) + pembrolizumab (Pembro) vs chemo + placebo as neoadjuvant/adjuvant treatment for patients (Pts) with gastric or gastroesophageal junction (G/GEJ) cancer

Abstract

Background: Pembro is FDA‐approved for the treatment of pts with recurrent locally advanced or metastatic G/GEJ adenocarcinoma whose disease has progressed on or after ≥ 2 prior therapies and whose tumors express PD‐L1 (combined positive score ≥ 1). Combining chemo with pembro in the neoadjuvant/adjuvant setting may benefit pts with locally advanced, resectable G/GEJ cancer. KEYNOTE‐585 (NCT03221426) is a phase 3, randomized, double‐blind study of chemo + pembro vs chemo + placebo as neoadjuvant/adjuvant treatment for locally advanced resectable G/GEJ cancer. Trial design: Eligibility criteria are age ≥ 18 years; previously untreated, resectable G/ GEJ adenocarcinoma (pts with Siewert type 1 tumors are eligible if initial treatment is planned perioperative chemo and resection), with no evidence of metastatic disease; planned surgery after preoperative chemo; adequate organ function; ECOG performance status 0/1; and no active autoimmune disease. Pts will be randomly assigned 1:1 to receive chemo + pembro (arm 1) or chemo + placebo (arm 2). Pts will receive neoadjuvant (preoperative) chemo +pembro every 3 weeks (Q3W) for 3 cycles or chemo + placebo Q3W for 3 cycles followed by surgery, then adjuvant chemo + pembro Q3W for 3 cycles or chemo + placebo Q3W for 3 cycles, then monotherapy with pembro or placebo Q3W for 11 cycles; overall treatment is up to 17 cycles. Chemo is cisplatin 80 mg/m2 IV on day 1 + either capecitabine 1000 mg/m2 orally twice daily ≥ 14 days or 5‐fluorouracil (5‐FU) 800 mg/m2 IV daily ≥ 5 days (investigator's choice). Pembro 200 mg IV is given on day 1. Adjuvant monotherapy is pembro (arm 1) or placebo (arm 2). In a separate safety cohort, 5‐FU 2600 mg/m2 IV+ docetaxel 50 mg/m2 IV+ oxaliplatin 85 mg/m2 IV+ leucovorin 200 mg/m2 IV (FLOT) is being studied as a potential chemo option. Primary end points are overall survival, event‐free survival per central review, and rate of pathologic complete response (no invasive disease and histologically negative nodes). Adverse events are graded and monitored for up to 90 days after treatment. Pts will be followed up for survival status. Planned enrollment is 860 pts.