Short-term results of VOLTAGE-A: Nivolumab monotherapy and subsequent radical surgery following preoperative chemoradiotherapy in patients with microsatellite stable and microsatellite instability-high locally advanced rectal cancer.

4100 Background: Chemoradiotherapy (CRT) followed by radical surgery (S) is standard therapy for patients (pts) with locally advanced rectal cancer (LARC). Sequential use of an anti-PD-1 antibody after radiation demonstrates synergistic effects in in vivo models, and an anti-PD-1 antibody is effective in pts with microsatellite instability-high (MSI-H) metastatic colorectal cancer (mCRC). We studied nivolumab (nivo) and radical S following CRT (50.4 Gy with capecitabine 1,650 mg/m 2 ) in T 3–4 N any M 0 LARC. Methods: After the quality-assured CRT, 240 mg q2 weeks x 5 cycles of nivo and radical S were investigated. In cohort A-1, for pts with microsatellite stable (MSS) LARC, the primary endpoint was a centrally confirmed pathological complete response (pCR) rate using AJCC tumor regression grading. The estimated required sample size assuming null and alternative hypotheses pCR = 10% and 30% was 37 pts, with a 1-sided alpha of 5% and power of 90%. In Cohort A-2, 5 pts with MSI-H LARC were included in an exploratory manner. Results: From Jan/2017 to Oct/2019, a targeted number of pts was included and assessed. In cohort A-1, 30% (11/37; 90% CI 18-44%) of pCR (AJCC grade (gr) 0) rate and 38% (14/37) of major pathological response (MPR) (AJCC gr 0+1) rate were observed. Clinical CR was observed in one additional pt (3%) refusing S after nivo. In cohort A-2, 60% (3/5) of pCR rate and 60% (3/5) of MPR rate were observed. As of Jan/2020, only 2 pts (1 local and 1 metastatic) in cohort A-1 and none in cohort A-2 recurred. Immune-related severe adverse events were observed in 3 pts (gr 3 myasthenia, gr 3 interstitial nephritis, and gr 2 peripheral motor neuropathy); all fully recovered and received radical S. During the follow-up period, one additional pt with gr 2 colitis was observed. No treatment-related deaths were observed. Conclusions: Promising pCR rates of 30% and 60%, with mild toxicities, were shown in MSS and MSI-H LARC pts treated with nivo plus radical S after CRT, suggesting the candidate therapy for the future non-surgical approach. Clinical trial information: NCT02948348 .