Repare Therapeutics (RPTX) Earnings Call Presentation

Study Overview - The MINOTAUR study investigates the combination of Lunresertib (Lunre), a PKMYT1 inhibitor, with FOLFIRI in advanced gastrointestinal cancers[1] - The study is ongoing but closed to enrollment (NCT05147350)[8, 10] - The primary objectives are to assess the safety, tolerability, recommended phase II dose (RP2D), and schedule of the combination[8] Preclinical Rationale - CCNE1 amplification and deleterious FBXW7 mutations, present in approximately 20% of GI cancers, are associated with poor prognoses and lack matched targeted therapies[5] - Lunre synergizes with irinotecan (iri) to enhance DNA damage and anti-tumor activity by abrogating iri-induced CDK1 phosphorylation[5] Clinical Trial Demographics - The study included 38 patients, with 18 (47.4%) having colorectal cancer (CRC) and 20 (52.6%) with other tumor types[10] - Among CRC patients, 77.8% (14/18) had RAS mutations, and 100% (18/18) had FBXW7 alterations[10] - Among other tumor patients, 35% (7/20) had RAS mutations, 60% (12/20) had CCNE1 amplification, and 40% (8/20) had FBXW7 alterations[10] Safety and Tolerability - The RP2D was established at 60mg BID (twice daily) of continuous daily dosing of Lunre[12] - The safety profile was consistent with FOLFIRI alone, with neutropenia being the most common Grade 3+ hematologic treatment-related adverse event (TRAE) observed in 31.6% (12/38) of patients[12, 13, 15] Efficacy - The overall response rate (ORR) was 18.2% (95% CI: 7-35.5)[17] - The clinical benefit rate (CBR) in CRC patients was 55.6% (10/18)[17] - 40% (2/5) of irinotecan-naïve CRC patients had a duration of treatment (DOT) greater than 9 months[17] - ctDNA molecular response rate (MRR) was 61% (14/23)[17]