Liposomal irinotecan combined with 5-FU/LV and bevacizumab as second-line therapy for metastatic colorectal cancer: A multicenter, single-arm phase II study (IRIS).

e15569 Background: For patients with metastatic colorectal cancer (mCRC) who progress after first-line oxaliplatin-based therapy, irinotecan-based regimens represent a standard second-line option. Liposomal irinotecan, designed to exploit the enhanced permeability and retention (EPR) effect, may improve tumor targeting while reducing systemic toxicity. This study evaluated the efficacy and safety of liposomal irinotecan combined with 5-FU/LV and bevacizumab as second-line treatment for mCRC. Methods: This was a multicenter, single-arm phase II study conducted across multiple institutions in China. Eligible patients were aged 18-75 years with histologically confirmed unresectable mCRC, progressive disease after first-line oxaliplatin-based therapy. Patients received liposomal irinotecan (70 mg/m²) + 5-FU (2400 mg/m²) + LV (400 mg/m²) + bevacizumab (5 mg/kg) on Day 1, every 2 weeks until disease progression or unacceptable toxicity. The primary endpoint was objective response rate (ORR) per RECIST v1.1. Secondary endpoints included disease control rate (DCR), duration of response (DoR), progression-free survival (PFS), overall survival (OS), and safety. Results: Between December 2023 and September 2025, 172 patients were enrolled and included in the full analysis set. At data cutoff, 60 patients remained on treatment and 112 had completed treatment. Median age was 60 years (range: 18-75), 57.6% were male, and 39.0% had rectal primary tumors. Among 111 efficacy-evaluable patients, the ORR was 18.0% (95% CI: 11.4–26.4%) and the DCR was 82.9% (95% CI: 74.6–89.4%). After a median follow-up of 4.7 months (range: 0.03-19.0), the median PFS was 7.8 months (95% CI: 5.54-9.96), and median OS was not reached. Subgroup analyses revealed longer PFS in patients with baseline CEA < 5 ng/L (9.3 vs. 6.5 months, p = 0.037) and in those who had not received bevacizumab in the first-line setting (9.6 vs. 6.1 months, p = 0.015). Treatment-related adverse events (TRAEs) occurred in 90.1% of patients, with grade ≥3 TRAEs in 43.6%. The most common grade ≥3 TRAEs were neutropenia (21.5%), leukopenia (13.4%), and diarrhea (8.7%). Serious adverse events (SAEs) occurred in 6.4% of patients, with no new safety signals identified. Conclusions: Liposomal irinotecan combined with 5-FU/LV and bevacizumab showed promising antitumor activity and a manageable safety profile as second-line therapy for mCRC. These results support this regimen as a valuable therapeutic option for patients progressing after oxaliplatin-based first-line treatment. Clinical trial information: NCT06184698 .