1513MO A phase II study of nivolumab plus low dose ipilimumab as first -line therapy in patients with advanced gastric or esophago-gastric junction MSI-H tumor: First results of the NO LIMIT study (WJOG13320G/CA209-7W7)

Microsatellite instability-high (MSI-H) is an established biomarker for response to immune checkpoint inhibitors. Herein, we report the efficacy and safety of nivolumab plus low-dose ipilimumab as first-line therapy in MSI-H advanced gastric or esophagogastric junction cancer (GC) patients from the phase II study. Eligible patients were unresectable advanced, recurrent, or metastatic GC with a histologically confirmed diagnosis of adenocarcinoma; confirmed MSI-H status with the MSI-IVD Kit (FALCO); no prior systemic anticancer therapy given as primary therapy for advanced or metastatic disease. Nivolumab (240 mg) biweekly and ipilimumab (1 mg/kg) every six weeks were given until disease progression or unacceptable toxicity. The primary endpoint was the objective response rate (ORR) assessed by a blinded independent central review (BICR). Secondary endpoints included disease control rate (DCR), progression-free survival (PFS), duration of response (DOR), overall survival (OS), and safety. Between November 2020 and Aug 2022, 29 patients were enrolled from 935 screened cases. The median age was 75 (range 54-84), and 44.8% of patients were male. At the data cut-off (December 12, 2022), 3 and 15 patients achieved confirmed complete and partial responses with ORR of 62.1% (95% CI: 42.3-79.3). The DCR was 79.3% (95% CI, 60.3-92.0). With the median follow-up of 9.0 months (range, 4.0-18.0), the median PFS was 13.8 (95% CI, 13.7-NR) months, and median DOR and OS were not reached yet. 12-month PFS and OS rates yielded 73% (95% CI, 52-86) and 80% (95% CI, 57-91), respectively. The most common reason for treatment discontinuation was adverse events. The safety profile was consistent with the known profiles of nivolumab plus low dose ipilimumab, and there were no unexpected safety signals. Treatment-related death was not observed. The chemo-free strategy with a combination of nivolumab and low-dose ipilimumab demonstrated high and robust efficacy with good tolerability in MSI-H GC patients.