Efficacy and safety of tislelizumab as neoadjuvant treatment in patients with stage II–III microsatellite instability-high/mismatch repair-deficient colorectal cancer: a single-arm, multicenter, open-label, prospective, phase II study

Background: In colorectal cancer (CRC), genomic microsatellite instability (MSI) indicates potential susceptibility to immune checkpoint blockade. Tislelizumab, a programmed cell death protein-1 inhibitor, has shown efficacy in MSI-high (MSI-H)/mismatch repair-deficient (dMMR) metastatic CRC. Methods: This prospective, single-arm phase II study (BGB-A317-214) aimed to evaluate the efficacy and safety of neoadjuvant tislelizumab in stage II–III MSI-H/dMMR CRC. Eligible patients received three cycles of neoadjuvant tislelizumab (200 mg intravenously) every 3 weeks, followed by radical surgery. The primary endpoint was investigator-assessed major pathological response (MPR) rate. Secondary endpoints included investigator-assessed pathological complete response (pCR) rate, event-free survival (EFS), and safety. Results: From January 2022 to June 2023, 33 patients were enrolled and received at least one cycle of neoadjuvant tislelizumab, and 29 received radical surgery. At primary analysis (data cutoff: 26 September 2023; median study follow-up: 6.5 range, 0.9–20.0 months), MPR and pCR rates were 89.7% (26/29 patients) and 62.1% (18/29 patients), respectively. MPR and pCR were consistent across the subgroups, including tumor location and clinical stage. With long-term follow-up (data cutoff: 3 January 2025; median study follow-up: 21.7 range, 0.9–35.2 months), the median EFS by investigator was not reached. The 1-year and 2-year EFS rates were both 93.9%. The safety profile of tislelizumab was well tolerated with no unexpected safety signals; one patient (3%) had a grade ≥3 treatment-related adverse event (abdominal inflammation). All other treatment-related adverse events were mild to moderate in severity. Conclusion: This study provides promising preliminary evidence for the efficacy and safety of neoadjuvant tislelizumab in patients with locally advanced MSI-H/dMMR CRC.