Repare Therapeutics announces intial data from Phase 1 MINOTAUR trial

Repare Therapeutics reported initial data from the ongoing Phase 1 MINOTAUR clinical trial evaluating lunresertib in combination with FOLFIRI in patients with advanced solid tumors. The data are being presented in a mini oral presentation by Elisa Fontana, M.D., Ph.D., Medical Director, Sarah Cannon Research Institute UK at the European Society of Medical Oncology Gastrointestinal Cancers Congress 2024, being held June 26-29 in Munich, Germany. Lunresertib is a first-in-class precision oncology small molecule PKMYT1 inhibitor that targets CCNE1 amplification, FBXW7 and PPP2R1A alterations in solid tumors. Lunresertib is being evaluated in combination with other therapies across several Phase 1 and Phase 2 clinical trials, as well as in multiple investigator-sponsored trials. Key Initial Findings from the Phase 1 MINOTAUR Clinical Trial: MINOTAUR is a Phase 1, multi-center, open-label, dose-scalation study to evaluate safety, pharmacokinetics, pharmacodynamics and preliminary anti-tumor activity of lunresertib in combination with FOLFIRI in advanced solid tumors. Primary objectives of the study were safety and tolerability, and determination of the recommended Phase 2 dose and schedule. Secondary objectives were pharmacokinetics, preliminary evidence of anti-tumor activity, pharmacodynamics, and circulating tumor DNA monitoring. As of May 2, 2024, the cutoff date for the data presented at the ESMO GI Congress, 38 patients were enrolled in the clinical trial. Preliminary RP2D established as 60mg BID lunresertib continuous plus standard FOLFIRI; Promising efficacy in heavily pretreated population with tumors that harbor CCNE1 amplification and FBXW7 mutation alterations; Overall response across tumor types was 18.2%, including four confirmed and two unconfirmed partial responses, regardless of prior irinotecan exposure; Prolonged clinical benefit rate across tumor types, primarily digestive system tumors, was 51.5%, including 46.7% of patients with recurrent colorectal cancer; Patients with CRC had prolonged duration of therapy, with 40% of irinotecan-naive patients and 20% of irinotecan-experienced patients on treatment for over nine months, compared to clinical benchmarks of 20% and 5-10%, respectively; ctDNA molecular response rate was 61% among evaluable patients; Lunresertib combination therapy was well tolerated without excess toxicity above expected rates for lunresertib or standard FOLFIRI alone; No safety-related treatment discontinuations at preliminary RP2D; Neutropenia and leukopenia were the most common Grade 3/4 treatment-related adverse events, consistent with that reported for FOLFIRI alone and reversible with FOLFIRI interruption; Rate of low-grade, reversible rash was consistent with lunresertib monotherapy experience.