Abstract
This is the first stage of the phase 1b/2 trial evaluating the effectiveness and safety of toripalimab, irinotecan, and bevacizumab in patients with rectal cancer refusing up-front surgery or radiation therapy (rectum cohort) and patients with T4NanyM0 colon cancer (colon cohort) with deficiency of mismatch repair (dMMR) or microsatellite instability (MSI). This trial allows a doctor-patient shared decision-making process to determine whether to omit irinotecan or bevacizumab and the optimal surgery timing. The primary endpoint pathological complete response (pCR) rates in the full analysis set (FAS) and per-protocol set (PPS) are 57.1% (95% confidence interval [CI] 28.9-82.3) and 66.7% (34.9-90.1), respectively, in the colon cohort (n = 14) and 75.0% (35.6-95.5) and 100% (51.7-100.0), respectively, in the rectum cohort (n = 8). No disease recurrence occurs in PPS. No grade 4-5 drug-related adverse events are observed. Toripalimab with or without irinotecan and bevacizumab shows promising efficacy and manageable toxicity in dMMR/MSI T4NanyM0 colon cancer and locally advanced rectal cancer (ClinicalTrials.gov: NCT04988191).