Phase II, single-arm trial of preoperative short-course radiotherapy followed by chemotherapy and camrelizumab in locally advanced rectal cancer

BACKGROUND: In locally advanced rectal cancer (LARC), preoperative short-course radiotherapy (SCRT) with delayed surgery has been shown to be as effective as long-course chemoradiotherapy, with only modest benefits. This study aimed to evaluate the efficacy and safety of preoperative SCRT combined with subsequent CAPOX (capecitabine and oxaliplatin) and the anti-PD-1 antibody camrelizumab in patients with LARC. METHODS: This was a prospective, single-arm, phase II trial. Treatment-naïve patients with histologically confirmed T3-4N0M0 or T1-4N+M0 rectal adenocarcinoma received 5×5 Gy SCRT with two subsequent 21-day cycles of CAPOX plus camrelizumab after 1 week, followed by radical surgery after 1 week. The primary endpoint was pathological complete response (pCR) rate. Biomarker analysis was performed to identify a potential predictor of pCR to treatment. RESULTS: From November 7, 2019 to September 14, 2020, 30 patients were enrolled, and 27 patients received at least one dose of CAPOX plus camrelizumab. Surgery was performed in 27 (100%) patients. The pCR (ypT0N0) rate was 48.1% (13/27), including 46.2% (12/26) for proficient mismatch repair (MMR) tumors and 100% (1/1) for deficient MMR tumors. Immune-related adverse events were all grade 1–2, with the most common being reactive cutaneous capillary endothelial proliferation (81.5%). No grade 4/5 adverse events occurred. Biomarker analysis showed patients without FGFR1–3 deletions had a better tendency for pCR. CONCLUSIONS: SCRT combined with subsequent CAPOX plus camrelizumab followed by delayed surgery showed a favorable pCR rate with good tolerance in patients with LARC, especially in the proficient MMR setting. A randomized controlled trial is ongoing to confirm these results. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov identifier: NCT04231552.