Abstract CT222: Phase Ib/II study of fruquintinib (F) combined with capecitabine (C) as maintenance therapy (MT) for RAS/BRAF wild-type metastatic colorectal cancer (mCRC) after first-line treatment with cetuximab combined with chemotherapy

Abstract Background: Continuous administration of cetuximab plus chemotherapy as first-line treatment for RAS/BRAF wild-type mCRC patients (pts) may bring cutaneous toxicities and resistance issues. However, the best maintenance strategy for these pts remains unclear. We conducted this study to explore the safety and efficacy of F (an anti-angiogenic inhibitor targeting VEGFR-1,2,3) combined with C as an oral regimen in MT of RAS/BRAF wild-type mCRC. Methods: The study enrolled pts with unresectable advanced metastatic colorectal adenocarcinoma who were RAS/BRAF wild-type and achieved disease control after up to 8 cycles of standard first-line cetuximab combined with chemotherapy. The study consisted of dose escalation (DES) and dose expansion (DEX) phases. The primary endpoint of the DES phase was the dose-limiting toxicities (DLTs) of F combined with C and the recommended phase II dose (RP2D) of F. The primary endpoint of the DEX phase was progression-free survival (PFS) from the start of MT until disease progression or death. Secondary endpoints were safety, disease control rate (DCR), and overall survival (OS, from the start of MT). We planned to enroll about 30 pts in the DEX phase. F (QD, days 1-14) was administered in combination with C (1g/m2 BID, days 1-14) every 21 days as MT. There were 3 dose levels for F: 3 mg/d, 4 mg/d, and 5 mg/d. The dose exploration was based on the ‘3+3’ dose escalation principle, with 4 mg/d as the starting dose. Results: As of January 5, 2025, 16 pts (median age: 61 years old; 25% female; primary tumor location: 81.3% sigmoid colon, 18.7% rectum; metastatic sites: 37.5% liver, 31.3% distant lymph nodes, 25% peritoneum, 6.3% lung, 25% none, 18.8% more than 1 organ) were enrolled (6 in DES, 10 in DEX). F dose level 5 mg/d on days 1-14 was determined as the RP2D (no DLTs were observed in 3 pts in F dose level 4 mg/d or 3 pts in F dose level 5 mg/d). Treatment-related adverse events (TRAEs) of any grade occurred in 14 (87.5%) pts. TRAEs of grade ≥ 3 was thrombocytopenia (1 patient, 6.3%). There were no serious TRAEs. 4 patients had their dose of furiquintinib reduced during treatment, 3 due to thrombocytopenia and 1 due to gingival pain. Of the 11 pts evaluable for response, DCR was 90.9% (95% CI: 62.3%, 98.4%). With median follow-up of 5.7 months, 5 pts had progressive disease, median PFS was not reached (95%CI: 4.1, NA). Two pts had duration of disease control of more than 430 days and one patient was still in treatment. OS is not yet mature. Detection and analysis of potent biomarkers related to drug activity is in progress. Conclusions: The RP2D of F was 5 mg/d on days 1-14 in this study. Our preliminary results showed that the efficacy of F combined with C is promising with well tolerance as MT in RAS/BRAF wild-type mCRC. Citation Format: Kai Ou, Biyang Cao, Wenwei Yang, Letian Zhang, Jingyu Lu, Lin Yang. Phase Ib/II study of fruquintinib (F) combined with capecitabine (C) as maintenance therapy (MT) for RAS/BRAF wild-type metastatic colorectal cancer (mCRC) after first-line treatment with cetuximab combined with chemotherapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_2):Abstract nr CT222.