A Phase 1 Study of Cabozantinib and Trifluridine/Tipiracil in metastatic colorectal adenocarcinoma

Abstract

This study determined the safety and Recommended Phase 2 Dose (RP2D) of the multi-kinase inhibitor cabozantinib in combination with trifluridine/tipiracil (TFT/TPI) in refractory metastatic colorectal carcinoma (mCRC). Single institution investigator-initiated phase 1 study using 3 + 3 design. Eligible mCRC patients had received prior standard regimens. Cabozantinib was given orally (p.o.) at 20 mg (dose level [DL] 0) or 40 mg (DL 1) daily on days 1–28, and FTD/TPI p.o. at 35 mg/m2 on days 1–5 and 8–12 every 28 days. Fifteen patients were enrolled. Median age 56 years (31–80), male (12/15), ECOG 0/1 = 9/6. Three patients were treated at DL 0 and another nine were treated at DL 1, none exhibiting a DLT. Most common any grade (G) treatment related adverse events (TRAE) were diarrhea (50%), nausea (42%), neutropenia (42%), fatigue (33%) and rash (25%). G3-4 TRAE were neutropenia (25%) and thrombocytopenia, hypokalemia, weight loss (each 8%). No serious TRAE or G5 were reported. The RP2D was determined to be DL 1. Median PFS was 3.8 months (95% CI 1.9–6.8) and disease control rate was 86.7%. The combination of cabozantinib and TFT/TPI is feasible and tolerable at standard doses and showed encouraging clinical activity in refractory mCRC. ClinicalTrials.Gov: NCT04868773