Tislelizumab plus bevacizumab and XELOX as first-line treatment of MSS/pMMR RAS-mutant metastatic colorectal cancer (TACTIC CRC-02): a phase II study

Background: The TACTIC CRC-02 study evaluated the efficacy and safety of tislelizumab, a humanized immunoglobulin G4 monoclonal antibody targeting programmed cell death protein 1, combined with standard XELOX plus bevacizumab as first-line treatment of microsatellite stable/proficient mismatch repair (MSS/pMMR) RAS-mutant metastatic colorectal cancer (mCRC).Patients and methods: TACTIC CRC-02 was a single-center, single-arm, open-label, phase II trial.Eligible patients had previously untreated, unresectable MSS/pMMR, RAS-mutant mCRC and an Eastern Cooperative Oncology Group performance status of 0 or 1. Patients received intravenous tislelizumab (200 mg/m 2 ), bevacizumab (7.5 mg/kg), and oxaliplatin (130 mg/m 2 ) on day 1, with oral capecitabine (1000 mg/m 2 twice daily) on days 1-14 of each 21-day cycle, for up to eight induction cycles followed by maintenance therapy.The primary endpoint was objective response rate (ORR) per RECIST 1.1.Secondary endpoints included progression-free survival, overall survival, and safety.Results: Between March 2023 and March 2024, 52 patients were enrolled and treated.At a median follow-up of 17.8 months [95% confidence interval (CI) 15.8 months-not reached), the primary endpoint was met with an ORR of 73.1% (95% CI 61.1% to 85.1%).The median progression-free survival was 9.6 months (95% CI 9.1-11.6months), and the median overall survival was not mature.Grade 3-4 treatment-related adverse events occurred in 21.2% of patients, with grade 3-4 immune-related adverse events occurring in 1.9%.No treatment-related deaths occurred.Conclusions: First-line treatment with tislelizumab plus XELOX and bevacizumab demonstrated a high ORR and a manageable safety profile in patients with MSS/pMMR, RAS-mutant mCRC.This chemo-immunotherapy combination represents a promising strategy and warrants further investigation in a phase III trial.