Neoadjuvant nivolumab plus ipilimumab and adjuvant nivolumab in patients (pts) with localized microsatellite instability-high (MSI)/mismatch repair deficient (dMMR) oeso-gastric adenocarcinoma (OGA): The GERCOR NEONIPIGA phase II study.

Abstract

244 Background: In pts with resectable gastric adenocarcinoma or OGA, radical surgery is the only curative option and perioperative chemotherapy seems worthless for those with MSI/dMMR tumors. Methods: We conducted phase II study evaluating the efficacy of neo-adjuvant nivolumab and ipilimumab followed by adjuvant nivolumab in pts with resectable MSI/dMMR, T2-T4 NxM0 tumors. Treatment consisted of nivolumab 240 mg every 2 weeks (6 infusions) and ipilimumab 1 mg/kg every 6 weeks (2 infusions), followed by radical surgery 5 weeks (±1 week) after last injection of nivolumab. Pts with Becker tumor regression grade (TRG) < 3 were treated with adjuvant nivolumab 480 mg every 4 weeks (9 infusions). The primary objective was pathological complete response (pCR) rate. Results: From 10/2019 to 06/2021, a total of 32 pts were enrolled (all had dMMR±MSI-H status; 16 with gastric cancer and 16 with OGA). The median age was 65.5 years (range, 40-80). Initial stage was: usT3Nx = 22, usT2Nx = 4, and usTxNx = 6 (not evaluable by ultrasound endoscopy). At data lock, 32 pts had terminated neo-adjuvant period and 27 (84%) completed all 6 neo-adjuvant cycles. 8 pts (32%) experienced G3/4 adverse events (AEs) during neo-adjuvant treatment. 29 pts underwent surgery; 2 refused surgery and had complete endoscopic response with tumor-free biopsies, 1 had surgery not performed in relation with a metastatic progression. The median delay between last injection and surgery was 35 days (extreme, 25-170). Overall surgical morbidity (54%, n = 14) was related to: anastomotic leakage = 4, pancreatitis = 2, pneumonia = 2, and other = 6. The incidence of post-operative mortality was 3.8% (n = 1) due to cardiovascular AE at post-operative day 3. All the 29 pts who underwent surgery had R0 resection: 17 (59%) had pCR (i.e., TRG 1a as per Becker grade, ypT0N0) and 4 (14%) had TRG 1b as per Beker grade (< 10% residual tumor per tumor bed). 1 pt had TRG 2 (10-50% of residual tumor) and 7 pts had TRG 3 (˃50% of residual tumor) as per Becker grade, per local pathological assessment (central pathological review is awaited). With a median follow-up of 10.9 months, 1 pt had metastatic relapse, 1 pt died without relapse and 30 pts were recurrence/progression-free. Conclusions: Neo-adjuvant therapy with nivolumab and ipilimumab is feasible and is associated with a high pCR rate in pts with MSI/dMMR resectable OGA. Data will be updated for the congress. Clinical trial information: NCT04006262.