32nd Annual Meeting and Pre-Conference Programs of the Society for Immunotherapy of Cancer (SITC 2017): Part Two
Authors: Yung-Jue Bang, Eric Van Cutsem, Charles Fuchs, Atsushi Ohtsu, Josep Tabernero, David Ilson, Jin Woo, Vivian Strong, Thorsten Goetze, Takaki Yoshikawa, Laura Tang, Linda Sun, Aisha Hasan, Minori Koshiji, Kohei Shitara, Antoni Ribas, David Hong, Anthony Tolcher, Ryan Sullivan, Geoffrey Shapiro, Bartosz Chmielowski, Les Brail, Lucy Lee, Suresh Mahabhashyam, Claudio Dansky Ullmann, Michael Postow, Jedd Wolchok, Amir Jazaeri, Robert Edwards, Emese Zsiros, Robert Brown, Igor Gorbatchevsky, Sam Suzuki, Maria Fardis, Robert Wenham, Kenneth Byrd, Nibedita Chakraborty, Mehmet Kocak, Alisa Harber, Ari Vanderwalde, Johann De Bono, Josep Piulats, Marine Gross-Goupil, Jeffrey Goh, Kristiina Ojamaa, Christopher Hoimes, Ulka Vaishampayan, Raanan Berger, Ahmet Sezer, Ronald De Wit, Charles Drake, Haiyan Wu, Christian Poehlein, Emmanuel Antonarakis
Journal: Journal for ImmunoTherapy of Cancer (2017)

BackgroundIn KEYNOTE-012 (NCT01848834) and KEYNOTE-059 (NCT02335411), pembrolizumab demonstrated manageable safety and promising antitumor activity alone or in combination with chemotherapy in patients with advanced G/GEJ cancer.Compared with chemotherapy alone, chemotherapy combined with pembrolizumab in the neoadjuvant/adjuvant setting can provide additional benefit to patients with locally advanced, resectable G/GEJ cancer.KEYNOTE-585 is a phase 3, randomized, double-blind study of chemotherapy combined with pembrolizumab versus chemotherapy combined with placebo as neoadjuvant/adjuvant treatment for locally advanced resectable G/GEJ cancer.Methods Key eligibility criteria in KEYNOTE-585 (NCT03221426) include age ≥18 years; previously untreated G/GEJ adenocarcinoma (Siewert type 2 or 3 tumors; Siewert type 1 tumor eligibility limited to those for whom planned treatment is perioperative chemotherapy and resection), with no evidence of metastatic disease; planning to undergo surgery after preoperative chemotherapy; Eastern Cooperative Oncology Group performance status 0-1; adequate organ function; no active autoimmune disease.Patients will be randomly assigned 1:1 to receive chemotherapy + pembrolizumab (arm 1) or chemotherapy + placebo (arm 2).Stratification factors are geographic region (Asia vs Non-Asia), primary tumor location (stomach vs GEJ), and tumor stage (II/III vs IVa).All patients will receive neoadjuvant (preoperative) chemotherapy + pembrolizumab every 3 weeks (Q3W) for 3 cycles or chemotherapy + placebo Q3W for 3 cycles followed by surgery and then adjuvant chemotherapy + pembrolizumab Q3W for 3 cycles or chemotherapy + placebo Q3W for 3 cycles followed by monotherapy with pembrolizumab or placebo Q3W for 11 cycles; treatment will continue for up to 17 cycles overall.Chemotherapy consists of cisplatin 80 mg/m 2 intravenously + either capecitabine 1000 mg/m 2 twice daily orally or 5fluorouracil 800 mg/m 2 intravenously (investigator's choice).Pembrolizumab 200 mg was administered intravenously.Adjuvant monotherapy consists of pembrolizumab (arm 1) or placebo (arm 2).Primary end points are overall survival (OS), event-free survival, and rate of pathologic complete response (defined as no invasive disease and histologically negative nodes) per central review.Adverse events (AEs) are graded per National Cancer Institute Common Terminology Criteria for Adverse Events v4.0 and will be monitored for 30 days after treatment end (90 days for serious AEs).Patients are followed up for survival every 12 weeks until death, withdrawal from study, or study termination.Planned enrolment is approximately 800 patients.