Trifluridine/tipiracil plus capecitabine and bevacizumab as upfront treatment for metastatic colorectal cancer: Results of the phase 1 TriComB study.

Abstract

3558 Background: Capecitabine (cap) plus Bevacizumab (bev) is a standard option for previously untreated unresectable metastatic colorectal cancer (mCRC) patients (pts) deemed not fit for upfront chemotherapy doublets. A synergistic effect of the sequential administration of cap and Trifluridine/Tipiracil (FTD/TPI) has been shown both in vitro and in vivomodels. Here, we present safety and preliminary activity results of the phase 1 TriComB study, an open-label, multicenter, phase 1/2 trial, evaluating FTD/TPI in combination with cap and bev in mCRC pts. Methods: Patients with previously untreated mCRC, ineligible for oxaliplatin- and/or irinotecan- based regimens, were enrolled. A 3 + 3 dose escalation design was used to identify the recommended dose (RD) of FTD/TPI (days 15-19 and 22-26) in combination with cap (1000 mg/sqm/BID days 1-14) and bev (5 mg/kg day 1,15) in 28-days cycles. Adverse events (AEs) were reported according to CTCAE version 5.0 and tumor response was assessed by RECIST version 1.1. Results: 11 pts (5 men, 6 women; median age: 77, range: 47-84 years) were enrolled. For the first three patients (FTD/TPI: 25mg/sqm BID) no dose limiting toxicities (DLTs) were observed. At 30 mg/sqm BID dose level, 3/5 DLTs were reported: 2 pts experienced a dose delay of >7 days from the scheduled timing and 1 patient was unable to receive ≥ 75% of study drugs’ doses during the first cycle. FTD/TPI was de-escalated and 3 additional patients were treated at 25 mg/sqm BID. Since 1/6 pts experienced a DLT (grade 4 colonic perforation) that was identified as the RD. Grade 3/4 AEs are listed in the Table. As of January 2024, Overall Response Rate is 72.7% (8/11 pts) and 66.7% (4/6 pts) in the overall population and at the RD, respectively. Conclusions: The sequential combination of cap and FTD/TPI with bev is feasible. The phase 2 of the study is ongoing to evaluate antitumor activity of this regimen in the same patients' population. Clinical trial information: NCT04564898 Safety summary Clinical trial information: NCT04564898 . [Table: see text]