Tislelizumab, bevacizumab, and chemotherapy as second-line therapy in PD-L1-positive, RAS-mutant metastatic colorectal cancer: A single-arm, phase II clinical trial.

Abstract

e15540 Background: The therapeutic options for RAS-mutant metastatic colorectal cancer (mCRC) post first-line therapy are limited, with suboptimal efficacy of standard second-line regimens. Preclinical and clinical data support the synergistic antitumor effect of anti-PD-1 and anti-VEGF agents. Methods: This single-arm phase II study enrolled 42 eligible RAS-mutant, PD-L1-positive mCRC patients who progressed after first-line fluoropyrimidine-based chemotherapy. Patients received tislelizumab, bevacizumab, and switched chemotherapy. The primary endpoint was 6-month progression-free survival (PFS) rate. Results: Between April 2023 and March 2025, 50 patients were screened and 42 patients were eligible. The primary endpoint was met, with a 6-month PFS rate was 66.67% (95% CI:53.83-82.56%). The confirmed ORR was 16.67% (95% CI: 6.97-31.36%), and DCR was 88.10% (95% CI: 74.37-96.02%). The median OS was 16.3 months (95% CI: 13.2-NA months). Treatment-related adverse events occurred in 76.7% of patients, with 4.76% being grade 3–4. Immune-related adverse events were grade 1-2 in 21.43% of patients. No treatment-related deaths occurred. Conclusions: This combination regimen showed promising efficacy and manageable safety, providing a potential therapeutic option for this patient population (ChiCTR2200066728). Clinical trial information: ChiCTR2200066728 .