A phase II study of nanoliposomal irinotecan with TAS102 and bevacizumab for patients with refractory metastatic colorectal cancer (mCRC).

161 Background: Metastatic colorectal cancer (mCRC) is a leading cause of cancer-related death. The combination of trifluridine/tipiracil (TAS102) and bevacizumab (bev) is a standard of care for patients with refractory disease. Nanoliposomal irinotecan (nal-IRI) is a well-tolerated chemotherapy with established activity in gastrointestinal malignancies. This study evaluates the addition of nal-IRI to TAS102/bev. Methods: A prospective, phase II, single arm clinical trial of nal-IRI with TAS102 and bevacizumab in participants with microsatellite stable (MSS) mCRC, previously treated with 5-fluorouracil (5FU), oxaliplatin, and irinotecan was conducted at the University of Wisconsin Carbone Cancer Center (NCT05854498). If RAS wild-type, prior anti EGFR-agent was required, and if RAS wild-type and HER2 amplified, prior HER2-targeted therapy was required. The primary endpoint of this study was to determine the progression free survival (PFS). Toxicities were graded according to CTCAE v5.0. Response was evaluated according to RECIST v1.1 criteria. Dosing was initiated at nal-IRI 60 mg/m2 on days 1 and 15, TAS102 35mg/m2 PO BID on days 1-5 and 15-19, and bev 5 mg/kg on days 1 and 15 of every 28-day cycles. The dosing of nal-IRI was modified to 50 mg/m2 after the first 6 subjects to enhance tolerability. Results: Between 10/2023 to 08/2025, 25 patients (9 females, 2 non-white, median age 57) were treated on study. 11/25 (44%) had KRAS wild-type disease. Median number of prior lines of therapy was 3 (range 2-11). Median follow-up time was 8.4 months. All 25 patients were evaluable for response. The best response was partial response in 1/25 (4%) patients, stable disease in 20/25 (80%) patients, and progressive disease in 4/25 (16%) patients. Disease control rate was 84% (21/25). The median PFS at data cut-off was 7.2 months. 6 patients remain on treatment. There have been no G4 treatment-related adverse events (TRAEs). Most common G3 TRAEs include abdominal pain in 2/25 (8%) patients, anemia in 3/25 (12%) patients, diarrhea in 3/25 (12%) patients, hypertension in 2/25 (8%) patients, lymphocyte count decreased in 3/25 (12%) patients. Conclusions: In this study, nal-IRI with TAS102 and bevacizumab was well-tolerated with no unexpected toxicities and shows encouraging results for treatment-refractory mCRC. Clinical trial information: NCT05854498 .