Abstract 449TiP
Background
In randomized clinical trials, regorafenib (REG) has demonstrated a benefit in overall survival (OS) in mCRC patients, but limiting toxicities make treatment discontinuation frequent. Managing the high inter-patient variability of REG pharmacokinetics (PK) should help prevent toxicity and prolong the anti-tumor effect. In the prospective TEXCAN study, a sum of plasma concentrations of REG and its two main active metabolites M2 and M5 (Csum) at Day15 of Cycle 1 within 2.5 - 5.5 mg/L was associated with an improved OS (1). Applying a pharmacological prospective dosing optimization strategy, the present study intends to confirm whether Csum would be a valuable biomarker to individualize REG dosage and improve OS in mCRC patients.
Trial design
RePERSO is the first multicenter (12 sites), open-label, prospective single-arm phase II study, assessing the clinical impact of Csum as a biomarker of treatment benefit in mCRC patients. Patients ≥18 years, with mCRC, ECOG PS 0-1, treated with REG after failure of fluoropyrimidine-based chemotherapy combined with oxaliplatin and/or irinotecan as well as EGFR and/or VEGF inhibitors are eligible. The initial dose of REG is 120 mg/day for 3 weeks/4 (1 cycle). At cycles 2 and 3, the dose of REG is adjusted according to Csum, toxicity and radiological response. The primary objective of the trial is to determine whether an “optimal exposure” to REG, based on Csum, is associated with improved OS in mCRC patients. “Optimal exposure” is defined as a Csum within the predefined range of 2.5-5.5 mg/L at C1 and/or C2. Secondary objectives include comparison of objective response rate, disease control rate and progression-free survival between patients with or without “optimal exposure”. In addition, exploratory objectives include assessments of the prognostic value of the ratio of M2-concentrations C2/C1, the impact of genetic polymorphisms on the PK of REG, the influence of sarcopenia and the impact of endogenous biomarkers on REG response. It is planned to include 100 patients in 12 months with a 1-year follow-up. First patient was enrolled in October 2021 and 24/100 patients have been enrolled by 30th April 2022. 1. Rousseau et al. Eur J Cancer.2022.
Clinical trial identification
NCT04874207 EUDRACT no.: 2021-000252-18.
Editorial acknowledgement
Legal entity responsible for the study
Centre Hospitalier Universitaire de Rennes.
Funding
Bayer Healthcare.
Disclosure
F. Lemaitre: Financial Interests, Personal, Other, Travel meeting: Chiesi; Non-Financial Interests, Personal, Other: Astellas; Non-Financial Interests, Personal, Invited Speaker: Sandoz. T. Lecomte: Non-Financial Interests, Personal, Advisory Board: Amgen, Servier, Sanofi, Merk; Financial Interests, Personal, Other, Travel accommodations expenses: Amgen, Servier, Sanofi. C. Tournigand: Financial Interests, Institutional, Funding, research project: Bayer. K. Bouhier Leporrier: Financial Interests, Other: IPSEN, Novartis; Non-Financial Interests, Other: IPSEN. J. Metges: Financial Interests, Personal, Other: Bayer, BMS, MSD. D. Tougeron: Financial Interests, Personal, Advisory Board: AstraZeneca, Sanofi, AMGEN, MSD, Roche, Servier, Servier, Pierre Fabre. F. Di Fiore: Other, Personal, Advisory Role: Roche, Amgen, Sanofi, Ipsen, Pierre Fabre, Servier, Janssens, Mylan, Sandoz, Bayer; Other, Personal, Leadership Role: Merk. C. Hervé: Financial Interests, Personal, Other, Travel accommodations: Sanofi, Servier. Y. Touchefeu: Non-Financial Interests, Personal, Advisory Board: MERK; Financial Interests, Personal, Other, Travel accommodations: MSD. B.J. Rousseau: Non-Financial Interests, Personal, Advisory Board: Bayer, Roche, Novartis, Gilead, Servier; Financial Interests, Personal, Other, Travel accommodations expenses: Bayer, Servier, Astellas. A. Lievre: Financial Interests, Personal, Advisory Board: AAA, BMS, Incyte, Pierre Fabre Oncologie, Servier, Astellas; Financial Interests, Personal, Invited Speaker: AAA, Amgen, Bayer, Ipsen, Mylan, Novartis, Pierre Fabre Oncologie, Roche, Sandoz, Sanofi, Servier, BMS, Leo-pharma, Viatris, Mylan; Financial Interests, Institutional, Invited Speaker: Incyte; Financial Interests, Personal, Other, registration and travel to medical congress: Boehringer, Ipsen, Mylan, Servier; Financial Interests, Personal, Other, registration and virtual medical congress (ASCO): Roche; Financial Interests, Personal, Other, Travel and meeting registration: Pierre Fabre Oncologie; Financial Interests, Institutional, Research Grant, RePERSO trial: Bayer; Financial Interests, Institutional, Invited Speaker, SOCRATE trial (FFCD promotion): Lilly; Financial Interests, Institutional, Research Grant, Given to INSERM: Novartis; Non-Financial Interests, Principal Investigator: Lilly, BMS, Incyte, Astra-Zeneca.
All other authors have declared no conflicts of interest.