A multi-center phase 1b/2 clinical trial of concurrent administration of fruquintinib and FTD/TPI in patients with previously treated unresectable metastatic colorectal cancer and gastric cancer (FACT).

TPS466 Background: Fruquintinib, an oral tyrosine kinase inhibitor targeting VEGF receptors (VEGFR)-1,2, and 3, was recently approved in Japan for patients with unresectable metastatic colorectal cancer (CRC) as a later-line therapy option. Trifluridine/tipiracil (FTD/TPI) has demonstrated efficacy as a later-line treatment for metastatic CRC and gastric cancer (GC). Previous clinical studies have suggested that the combination of FTD/TPI with a VEGF inhibitor may provide enhanced antitumor activity and prolong survival in CRC and GC. This study aims to evaluate the efficacy and safety of fruquintinib in combination with FTD/TPI in patients with unresectable advanced or recurrent CRC and GC. Methods: The FACT trial is an investigator-initiated, open-label, single-arm, multicenter phase 1b/2 study. Eligible patients are aged 18 years or older with histologically confirmed unresectable or metastatic CRC or GC who have received standard chemotherapy regimens and are refractory or intolerant to them. Patients receive fruquintinib (5 mg once daily, orally) on days 1–21, and FTD/TPI (35 mg/m² twice daily, orally) on days 1–5 and 8–12 of each 28-day treatment cycle. Phase 1b employs a standard 3+3 dose de-escalation design to evaluate dose-limiting toxicity (DLT) and determine the recommended phase 2 dose (RP2D) of fruquintinib. If patients are intolerant to fruquintinib at 5 mg, the dose may be reduced to 4 mg. In phase 2, patients receive the RP2D. The primary endpoints are the incidence of dose-limiting toxicity (DLT) in phase 1b and disease control rate (DCR) assessed by investigators in phase 2. Secondary endpoints include objective response rate, progression-free survival, duration of response, overall survival, and incidence of adverse events. In this study, the DCR threshold is set at 40% and the expected value at 65%. With a one-sided significance level of 5% and 80% power, the required sample size is calculated to be 28 using exact binomial distribution. The planned sample size is 30 for each of CRC and GC. Enrollment commenced in June 2025 (jRCT2031240630). Phase 1b have been completed without DLT. Enrollment to phase 2 began in August 2025. Clinical trial information: jRCT2031240630 .