Phase I multicenter, open-label study to establish the maximum tolerated dose (MTD) of trifluridine/tipiracil and oxaliplatin combination in patients (pts) with metastatic colorectal cancer (mCRC)
Session type: Poster / e-Poster / Silent Theatre session
Preclinical evidence suggests improved efficacy when combining trifluridine/tipiracil with oxaliplatin compared to each monotherapy. The primary objective was to determine the safety and MTD among mCRC pts who have progressed after at least one prior line of treatment.
This is a two-part study, starting with a 3+3 design, where pts received escalating trifluridine/tipiracil doses together with a fixed dose of oxaliplatin 85mg/m² (day 1). The second part combines this doublet with either bevacizumab or nivolumab to assess safety, pharmacokinetics and efficacy of each triplet.
Fifteen of 17pts were evaluable for DLTs. Median age was 61 years (range 32-74), 11 and 6pts had an ECOG PS of 0 and 1, respectively; 76% received ≥2 lines including for 10pts previous line with oxaliplatin. Pts received a median of four cycles (range:1–23). The MTD was defined at trifluridine/tipiracil 35mg/m² bid and oxaliplatin 85mg/m² days 1-5 q14. Combination was well tolerated and only one DLT was observed (G3 febrile neutropenia). The most common (>20%) non-hematologic adverse drug reactions (ADRs) included nausea, asthenia, vomiting, diarrhea and decreased appetite. Moderate-to-severe neutropenia occurred in 5pts and thrombocytopenia in 4pts (all G1); 1pt experienced a G4 anemia at Cycle 4. Oxaliplatin-related neurotoxicity G≥2 was observed in 2pts. ADRs were manageable with basic supportive care, with treatment delays or interruptions. Best overall response includes partial response (n=1, unconfirmed), stable disease (n=7).
At the MTD, incidence and severity of bone marrow suppression and gastrointestinal toxicities were similar to previously published data. A cohort of 6 additional pts will confirm the MTD. The second part of this study is now underway and has recently opened in the UK. Clinical trial: NCT02848443.