The CREAFORMO-004 study: A phase II study of HR070803 plus 5-fluorouracil/leucovorin and bevacizumab as second-line treatment in patients with metastatic colorectal cancer.

e15525 Background: Irinotecan-based regimens are commonly used as second-line therapy for metastatic colorectal cancer (mCRC). Irinotecan liposomes can improve the distribution and metabolism through enhanced permeability and retention effect. This study explored the efficacy and safety of irinotecan liposome (HR070803) in combination with 5-fluoruracil/leucovorin (5-FU/LV) and bevacizumab as a second-line treatment for patients with mCRC. Methods: In this phase 2 study (ChiCTR2300075966), patients with histologically confirmed mCRC who had failed prior first-line chemotherapy (fluoropyrimidine plus oxaliplatin, with either bevacizumab or an anti-EGFR antibody for RAS wild-type tumors) were eligible for enrollment. Exclusion criteria included patients with pathologically confirmed pMMR/MSI-H, BRAF V600E mutation, or prior irinotecan-based therapy. Bevacizumab (5.0 mg/kg), HR070803 (60 mg/m²), and 5-FU/LV (2400/400 mg/m²) were administered every two weeks until disease progression. The primary endpoint was the objective response rate (ORR) according to RECIST version 1.1. Secondary endpoints included disease control rate (DCR), duration of response (DoR), progression-free survival (PFS), overall survival (OS), quality of life, and tolerability. Results: From January 15, 2024, to December 27, 2024, 34 patients were enrolled. The median age was 58 years (range, 26–73), with 76.5% of patients being male and 73.5% having left-sided colon or rectal cancer. KRAS mutations were present in 41.2% of patients, and 2.9% had ERBB2 amplification. Hepatic metastases were observed in 76.5% of patients, and 58.8% had metastatic involvement of more than one organ. Of the 27 patients with evaluable treatment efficacy, the confirmed ORR was 29.6% (8/27 patients; 95% CI, 12.2-48.0), and the DCR was 81.5% (22/27 patients; 95% CI, 65.8-97.1). Median DoR, PFS, and OS were not yet reached. Treatment-related adverse events (TRAEs) of grade 3 or 4 occurred in 47.1% of patients (16/34); the most common TRAEs were hematologic and gastrointestinal. TRAEs leading to treatment discontinuation occurred in 2 patient (5.9%). Conclusions: Irinotecan liposome (HR070803) in combination with 5-FU/LV and bevacizumab demonstrated promising efficacy and durability in this patient population. These results support further investigation of irinotecan liposome (HR070803) as a treatment option for patients with mCRC. Clinical trial information: ChiCTR2300075966 .