Cadonilimab combined with FOLFIRINOX and bevacizumab as first-line treatment for microsatellite stable/proficient mismatch repair metastatic colorectal cancer: Updated survival analysis and safety outcomes from a multicenter, single-arm, phase 2 study (SYLT-026).

Abstract

121 Background: This study evaluated the efficacy and safety of combining cadonilimab with FOLFIRINOX (irinotecan, oxaliplatin, leucovorin, and fluorouracil) and bevacizumab as first-line therapy for pMMR/MSS mCRC. Methods: In this multicenter, single-arm, phase II trial, we enrolled treatment-naive patients (aged 18–75 years) with unresectable pMMR/MSS mCRC, an ECOG PS of 0-2, and ≥1 measurable lesion (per RECIST v1.1). Patients received FOLFIRINOX (irinotecan 165 mg/m², oxaliplatin 85 mg/m², L-leucovorin 200 mg/m², fluorouracil 2400 mg/m² as a 48-hour infusion), bevacizumab (5 mg/kg), and cadonilimab (6 mg/kg) every 14 days for up to 12 cycles, followed by maintenance therapy with fluoropyrimidine, bevacizumab, and cadonilimab for up to 52 weeks or until disease progression, unacceptable toxicity, or withdrawal of consent. Patients were stratified by liver metastasis status (n =10 with and n =10 without). The primary endpoint was objective response rate (ORR). Results: Between November 16, 2023, and July 26, 2024, 20 patients were enrolled. The ORR was 100% with all partial responses (PR). As of data cutoff (September 1, 2025), the median follow-up was 17.18 months (lQR 15.18-18.99). The median PFS was 16.03 months, and the median OS was not yet mature. The median PFS between the liver metastasis subgroup and the non-liver metastasis subgroup was (NA vs 14.75 m; p = 0.32), the median OS of both subgroups was not reached. No significant difference in 12-month PFS rate was observed between the liver metastasis subgroup (90% [95% CI: 73.2–100%]) and the non-liver metastasis subgroup (64% [95% CI: 37.4–100%]), p = 0.71; while the 12-month OS showed an approached statistical significance (100% [95% CI: 100–100%] vs 64% [95% CI: 37.4–100%]; p = 0.051). Hypoalbuminemia (75%), anemia (70%), and fatigue/asthenia (65%) were common adverse events but most patients were grade 1 - 2. Other notable adverse events included stomatitis (55%), proteinuria (50%), and diarrhea (50%), 5% of which were grade 3. Six (30%) patients experienced at least one irAEs of any grade, and 4 (20%) developed grade 3 (G3) adverse events, 2(10%) patients developed multiple irAEs involving more than one organ system. The details were grade 3 dermatitis (n = 3), grade 3 hepatitis (n = 1), grade 3 colitis (n = 1), grade 2 myositis (n = 1), grade 2 colitis (n = 1) and grade 1 dermatitis (n = 1). irAEs led to cadonilimab discontinuation in 4(20%) patients. Conclusions: Cadonilimab combined with FOLFOIRINOX and bevacizumab demonstrated promising survival and acceptable toxicity as first-line therapy for pMMR/MSS mCRC. These findings support further validation in phase 3 randomized trial. Clinical trial information: NCT05839470 .