CheckMate-032: Phase I/II, open-label study of safety and activity of nivolumab (nivo) alone or with ipilimumab (ipi) in advanced and metastatic (A/M) gastric cancer (GC).

Abstract

4010 Background: Chemotherapy-refractory GC is a uniformly fatal illness and an unmet therapeutic need. Nivo is a fully human anti-PD-1 monoclonal antibody with a manageable safety profile and efficacy in solid tumors. We report results of a completed A/M GC cohort of CheckMate-032 study evaluating nivo monotherapy and nivo with ipi in pts with solid tumors. Methods: Pts with A/M, histologically confirmed GC, esophageal (EC), or gastroesophageal junction cancer (GEC), irrespective of PD-L1 status, who had progressed on chemotherapy, were treated with nivo 3 mg/kg Q2W (N3), nivo 1 mg/kg + ipi 3 mg/kg (N1+I3), or nivo 3 mg/kg + ipi 1 mg/kg (N3+I1) Q3W x 4 cycles, followed by nivo 3 mg/kg Q2W until confirmed disease progression or intolerable toxicity. Primary endpoint was ORR; other endpoints included safety, OS, and biomarker status. Results: 160 pts with A/M GC were treated with N3 (n = 59), N1+I3 (n = 49), or N3+I1 (n = 52). Baseline characteristics were comparable across cohorts; the majority of pts had ≥ 2 prior regimens. Treatment-related AEs (TRAE) of any grade occurred in 70% (N3), 84% (N1+I3), and 75% (N3+I1) of pts; Grade 3-4 TRAEs occurred in 17%, 45%, and 27% of pts. 12% of pts stopped therapy due to treatment toxicity: 5% (N3), 22% (N1+I3), and 12% (N3+I1). Treatment-related serious AEs (TRSAEs) of any grade and Grade 3-4 TRSAE occurred in 10% and 5% (N3), 43% and 35% (N1+I3), and 23% and 15% (N3+I1) of pts. There was one Grade 5 TRSAE of tumor lysis syndrome (N3+I1). 154 (96%) pts were evaluable for efficacy with the confirmed ORR 16%: 14% (N3), 26% (N1+I3), and 10% (N3+I1), including 2 pts with CR (1 in N3; 1 in N1+I3) and a disease control rate (ORR+SD) of 38%. OS data are in the Table below with 15 pts (9%) remaining on therapy. Updated biomarker data will be presented. Conclusions: TRAEs for nivo and nivo + ipi were consistent with those previously reported. Clinical activity and OS in pts with chemotherapy refractory disease are encouraging. These data support ongoing evaluation of nivo and nivo + ipi in A/M GC/EC/GEC. Clinical trial information: NCT01928394. N3 N1+I3 N3+I1 OS Rate, % (95% CI) 6 mo 49 (35–62) 54 (39–67) 43 (29–57) 12 mo 36 (21–51) 34 (19–50) NA Median OS, mo (95% CI) 5.0 (3.4–12.4) 6.9 (3.6–NA) 4.8 (3.0–9.1)