Liposomal irinotecan plus bevacizumab in irinotecan-refractory metastatic colorectal cancer: A multicenter, phase I/II trial.

e15545 Background: lrinotecan-based chemotherpy is a standard treatment in metastatic colorectal cancer (mCRC). Liposomal irinotecan is a nanoliposomal formulation of irinotecan which has improved pharmacokinetics (PK) and tumor distribution of irinotecan and its active metabolite, SN-38. However, the efficacy and safety of liposomal irinotecan in patients who previously received irinotecan-based chemotherapy remain unclear. This phase I/II study was designed to determine the maximum tolerated dose (MTD), and explore the efficacy of liposomal irinotecan plus bevacizumab in irinotecan-refractory mCRC patients. We report the results of the phase I portion of the study preceding the initiation of the phase II study. Methods: Patients who had progressed during or within three months after treatment with an irinotecan-based regimen received liposomal irinotecan plus bevacizumab (5mg/kg) every 2 weeks until disease progression, or unacceptable toxicity. Phase I was a dose-escalation study of liposomal irinotecan, using a conventional 3+3 design to determine the MTD. The starting dose of liposomal irinotecan was 70 mg/m 2 and escalated by 10 mg/m 2 to the target dose of 90 mg/m 2 . Results: The study completed dose-escalation part (70 to 90 mg/m 2 ) as of cutoff date (December, 2024). A total of 12 patients were enrolled, with a media age of 61.5 (range: 40-74) years. All patients had received ≥2 prior lines therapy, 5 patients (41.7%) had received ≥3 prior lines therapy, and 5 patients (41.7%) had more than 2 metastatic sites. 33.3% of the tumors were located in the right colon, 25.0% in the left colon and 41.7% in the rectum. Dose-limiting toxicity was not observed in per dose level. The target dose of 90 mg/m 2 was determined to be the MTD. Treatment-related adverse events (TRAEs) occurred in 12 patients (100.0%), and 6 patients (50.0%) experienced grade 3-4 AEs. Grade 3-4 TRAEs included diarrhea (50.0%), neutropenia (8.3%), leucopenia (8.3%), which had recovered after symptomatic treatment. No unexpected adverse events and grade 5 TRAE occurred. 8 patients underwent at least one tumor assessment. Among them, 6 patients achieved stable disease, 2 patients had progressive disease. The DCR was 75.0% (95%CI 34.9%-96.8%), and median PFS and median OS were not reached yet. Conclusions: The results showed that liposomal irinotecan (90 mg/m 2 ) plus bevacizumab (5mg/kg) every 2 weeks had tolerable toxicity and promising efficacy. Phase II study is currently ongoing. Clinical trial information: NCT06434090 .