Liposomal irinotecan (HR070803) plus fluorouracil and bevacizumab as second-line treatment in advanced colorectal cancer: Cohort A results from a phase 2 trial.

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Background: Irinotecan-based regimens are standard second-line therapy for advanced colorectal cancer (CRC). Liposomal irinotecan (Lipo-IRI, HR070803) may offer improved safety and efficacy. This study investigated Lipo-IRI combined with fluorouracil and targeted therapy in this setting. Methods: This is an ongoing multicenter, two-cohort phase 2 trial (NCT06540326). Cohort A results are reported. Patients with relapsed/metastatic CRC after first-line therapy received Lipo-IRI (60 mg/m², q2w), 5-FU/leucovorin (modified de Gramont regimen, q2w), and bevacizumab (5 mg/kg, q2w) for 6-9 cycles, followed by maintenance therapy until progression or intolerance. The primary endpoint was objective response rate (ORR). Results: Between Nov 2024 and Oct 2025, 53 patients were enrolled in Cohort A. In the efficacy-evaluable set (n=46), the unconfirmed ORR was 26.1% (12/46; 95% CI, 14.3-41.1) and the confirmed ORR was 21.7% (10/46; 95% CI, 10.9-36.4). With a median follow-up of 5.5 months, the median progression-free survival (PFS) was 7.4 months (95% CI, 4.9-not reached). Grade ≥3 treatment-related adverse events occurred in 18.9% of patients, most commonly decreased neutrophil count (7.5%). Diarrhea (any grade) occurred in 9.4% of patients (grade ≥3: 1.9%). Conclusions: Lipo-IRI combined with fluorouracil and bevacizumab shows promising efficacy and a manageable safety profile as a second-line treatment for advanced CRC, suggesting it may be a good therapeutic option. Clinical trial information: NCT06540326 .