A phase 1b/2, study of nivolumab following preoperative chemoradiotherapy in patients with resectable rectal cancer

The standard treatment for patients (pts) with locally advanced rectal cancer is the fluoropyrimidine-based chemoradiotherapy (CRT) and subsequent radical surgery. As the pathological complete response (pCR) of CRT ranged 8-17%, more powerful treatment has been desired. The synergistic effects of anti-PD-1 antibody and radiation have already been demonstrated in various in vivo models. This is a phase Ib/II, open-label, single-arm, multicenter study to investigate the safety, efficacy, and proof of concept of nivolumab (Nivo) and surgery as a sequential therapy following CRT in pts with locally advanced resectable rectal cancer. In phase Ib part, we evaluate the safety and dose-limiting toxicity, and decide a recommended dose (RD). In phase II part, we evaluate the efficacy and safety of Nivo and surgery at the RD. The primary endpoint is the pCR rate determined by central assessment in pts with microsatellite-stable (MSS)/microsatellite instability low (MSI-L) tumors. Disease-free survival, overall survival, and safety will be evaluated as secondary endpoints. In exploratory analysis, we also evaluate the biomarkers related to therapeutic response to preoperative CRT and Nivo.