Efficacy and safety of cadonilimab plus chemotherapy and bevacizumab as second-line treatment in patients with <i>RAS</i> -mutant metastatic colorectal cancer: Preliminary findings of a multi-center, single-arm study.

Abstract

e15602 Background: To date, immune-checkpoint inhibitors remain ineffective for patients with proficient mismatch repair/microsatellite stable (pMMR/MSS), metastatic colorectal cancer (mCRC). Chemotherapy plus targeted therapy represents standardized therapeutic regimens in second-line treatment of patients with pMMR/MSS mCRC. Preclinical and clinical studies have suggested that addition of immune-checkpoint inhibitors to standardized treatments have synergistic therapeutic effects in pMMR/MSS mCRC, especially in RAS-mutant patients. Therefore, this study aims to investigate whether the addition of cadonilimab (a humanized bispecific antibody targeting both PD-1 and CTLA-4) to chemotherapy and bevacizumab as second-line treatment could improve efficacy while maintaining safety in pMMR/MSS, RAS-mutant mCRC patients. Methods: This open-label, single-arm, multi-center study enrolled eligible patients with pMMR/MSS, RAS-mutant mCRC patients, aged 18-75, who were previously treated with oxaliplatin-based chemotherapy as first-line treatment, had at least one measurable lesion according to RECIST 1.1, ECOG performance status (PS) of 0–1, and adequate organ function. Participants received cadonilimab (6 mg/kg) plus FOLFIRI and bevacizumab (5 mg/kg) for up to twelve 14-day cycles, followed by maintenance therapy including cadonilimab and fluoropyrimidine with bevacizumab until PD or unacceptable toxicities. The primary endpoint was objective response rate (ORR) per RECIST 1.1 by investigator review. The secondary endpoints included disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and safety and tolerability. Results: In total, 32 eligible patients were enrolled between February 2024 to December 2025 from three centers. Among the 27 efficacy-evaluable patients, the regimen yielded an objective response rate (ORR) of 44.4% (12/27) and a disease control rate (DCR) of 70% (19/27). Median progression-free survival (PFS) and overall survival (OS) have not yet been reached. Grade ≥3 treatment-related adverse events (TRAEs) occurred in 7 of 32 patients (21.9%). The most common TRAE was decreased neutrophil count, followed by diarrhea, fatigue, infusion-related reaction and elevated alanime aminotransferase. Conclusions: Cadonilimab plus chemotherapy and bevacizumab shows an encouraging clinical efficacy and tolerable safety as second-line treatment among pMMR/MSS, RAS-mutant mCRC patients. Clinical trial information: NCT07253896 .