Efficacy and safety of regorafenib plus biweekly TAS-102 for refractory metastatic colorectal cancer (REGTAS): A multicenter single-arm phase II trial.

e15567 Background: Both regorafenib and TAS-102 have shown significant, but limited survival benefits for metastatic colorectal cancer (mCRC) patients who progressed after standard treatments. Due to their unique mechanisms of action and non-overlapping toxicities, a preliminary phase I study (REMETY) has demonstrated that regorafenib combined with TAS-102 in a four-week standard schedule was feasible and safe, but at the cost of recommended phase II dose of TAS-102 being 25 mg/m2 BD. This study aimed to evaluate the efficacy and safety of biweekly TAS-102 plus regorafenib in refractory mCRC. Methods: REGTAS is a multicenter phase II trial involving patients with chemo-refractory mCRC. Prior treatment with 5-FU, oxaliplatin, irinotecan, anti-VEGF antibody and anti-EGFR antibody for RAS wild type was required. Regorafenib was administered at 120 mg/day for 21 days in a four-week cycle, or a dose-escalation strategy (80 mg/day, followed by weekly increase of 40 mg to 120 mg/day). TAS-102 was given biweekly (30mg/m2 BD, on Day 1-5). The primary endpoint was progression-free survival (PFS). The secondary endpoint included safety, disease control rate (DCR) and overall survival (OS). Results: From March 1st 2022 to December 31st 2022, 16 patients were enrolled form five centers. All patients received at least one cycle of treatment, and 13 patients had at least one evaluation. The median age was 56.5 years old including 9 (52.9%) males. 11 (68.7%) patients were enrolled within 18 months from diagnosis of mCRC. RAS and BRAF mutation were detected in 8 (50.0%) and 1 (6.3%) patients. Among 13 evaluable patients, 11 achieved SD and 2 had PD, with the DCR of 84.6% (95% CI: 54.6%-98.1%). The median PFS was 4.9 months (95% CI: 2.8-7.0). Twelve patients were alive, and the median OS was not reached. All patients experienced treatment-related adverse events (TRAEs) and 4 (25.0%) had grade 3 or higher TRAEs. No grade 5 TRAE occurred. The most common TRAEs of any grade were hand-foot syndrome (62.5%), hypertension (68.8%), fatigue (50.0%), neutropenia (43.8%), thrombocytopenia (31.3%) and alanine aminotransferase increased (25.0%). Conclusions: Regorafenib plus biweekly TAS-102 exhibited promising benefits in terms of DCR and PFS, and could be a novel treatment option for patients with refractory mCRC. The adverse events were generally tolerable and manageable. Further studies are needed to confirm these preliminary findings. Clinical trial information: The registration number is still under approval .