CheckMate 649: A randomized, multicenter, open-label, phase 3 study of nivolumab (nivo) + ipilimumab (ipi) or nivo + chemotherapy (CTX) vs CTX alone in pts with previously untreated advanced (adv) gastric (G) or gastroesophageal junction (GEJ) cancer.

Abstract

TPS4132 Background: Pts with adv G/GEJ cancer have an OS of ≈ 1 y, indicating an unmet medical need for new first-line treatments (Tx). Expression of the PD-1 ligands PD-L1/PD-L2 is observed in up to 40% of pts with G/GEJ cancer and is associated with poor prognosis. In a phase 3 study of the PD-1 inhibitor nivo vs placebo in pts with adv CTX-refractory (CTX-R; ≥ 2 lines) G/GEJ cancer, nivo reduced the risk of death by 37% (HR, 0.63; P < 0.0001) and increased the OS rate at 12 mo (27% vs 11%; Kang YK, et al. J Clin Oncol. 2017;35 (suppl 4S) [abstract 2]). In a phase 1/2 study in pts with CTX-R G/GEJ/esophageal cancer (79% ≥ 2 prior Tx lines), nivo 1 mg/kg + ipi 3 mg/kg had a manageable safety profile and resulted in 26% ORR (44% ORR in pts with PD-L1+ tumors), a median OS of 6.9 mo, and a 34% OS rate at 12 mo (Janjigian Y, et al. ASCO, 2016 [abstract 4010]). In the phase 1 CheckMate 012 trial, nivo + CTX had clinical activity and manageable safety in pts with NSCLC (Rizvi NA, et al. J Clin Oncol. 2016;34:2969-2979). These positive results support investigation of nivo, nivo + ipi, and nivo + CTX in earlier lines of Tx for G/GEJ cancer. The open-label, phase 3 CheckMate 649 trial will evaluate nivo + ipi and nivo + CTX vs CTX alone as first-line Tx for pts with adv G/GEJ cancer (NCT02872116). Methods: 1266 pts aged ≥ 18 y with untreated, inoperable adv/metastatic G/GEJ cancer (histologically confirmed adenocarcinoma) regardless of PD-L1 status will be randomized to receive either nivo + ipi, nivo + CTX (capecitabine/oxaliplatin [XELOX] or fluorouracil/leucovorin/oxaliplatin [FOLFOX]), or investigator choice of XELOX or FOLFOX. Tumor tissue for determination of PD-L1 status (Dako assay) must be provided from ≤ 6 mo before study Tx. No prior systemic Tx, including HER2 inhibitors, are allowed. Pts with known HER2+ status, suspected autoimmune disease, grade > 1 peripheral neuropathy, or active infection are excluded. Primary endpoint is OS in pts with PD-L1+ (≥ 1%) tumors. Other endpoints include OS in all pts; PFS and time to symptom deterioration in all pts and in pts with PD-L1+ tumors; and safety. Clinical trial information: NCT02872116.