Neoadjuvant chemoradiotherapy plus sintilimab in proficient mismatch repair locally advanced rectal cancer with intermediate/high-immunoscore (SILAR): a single-arm phase II trial.

There is an urgent need to identify those who may benefit from immunotherapy-based chemoradiotherapy (CRT) for patients with locally advanced rectal cancer (LARC) with proficient mismatch repair (pMMR). This single-arm, phase-II trial (NCT05450029), enrolled 46 treatment-naïve patients with histologically confirmed T3-4N0M0 or T1-4N+M0 LARC with intermediate or high Immunoscore. Patients received 6 cycles of mFOLFOX6 and long-course radiotherapy (50 Gy in 25 fractions) followed by surgery. Sintilimab was added during CRT (2nd-6th cycle). The primary endpoint, pathologic complete response (pCR) rate, was 65.2% [30/46, 95%CI: 49.7-78.6], with 85.7% (6/7) in high and 61.5% (24/39) in intermediate Immunoscore, meeting the pre-specified primary endpoint. Secondary endpoints included R0 resection rate (97.8%), the clinical tumor response (ORR 93.5%), the complication rate and safety, 3-year event-free survival rate, and 3-year overall survival rate (immature). The most common treatment related adverse event (TRAE) was leukopenia (69.6%, 32/46). The TRAE of Grade 3 occurred in 7 patients (15.2%). Four patients had postoperative complications (all grade ≤2). Here, we showed that PD-1 blockade combined with long-course CRT yielded promising therapeutic effects with a favorable pCR rate and acceptable safety profile among patients with intermediate/high-Immunoscore pMMR LARC.