Repare Therapeutics Inc. (Nasdaq: RPTX) is making strides in its clinical-stage precision oncology programs, with key updates presented across its pipeline. The company is on track to report data from the MYTHIC dose expansion clinical trial in December 2024, evaluating lunresertib in combination with camonsertib at the recommended Phase 2 dose (RP2D). This combination is being assessed in patients with platinum-resistant ovarian and endometrial cancers, specifically those harboring CCNE1 amplification or FBXW7 or PPP2R1A mutations.
Lunresertib (RP-6306) Clinical Updates
Lunresertib, a first-in-class, oral PKMYT1 inhibitor, is currently being evaluated in the MYTHIC trial. Repare plans to report data from approximately 20-30 patients in each cohort in December 2024, with the intention of initiating a registrational trial in 2025. Updated safety and tolerability data from the Phase 1 MYTHIC trial, presented at the 36th EORTC-NCI-AACR Symposium, highlighted the benefits of an individualized schedule for managing anemia. This approach demonstrated a reduction in Grade 3 anemia from 51.4% to 22.6% through dose optimization, while maintaining clinical benefit. Notably, no thrombocytopenia or serious neutropenia was observed in these patients.
Data presented at the AACR Ovarian Cancer Research Symposium underscored the impact of alterations in FBXW7, PPP2R1A, and CCNE1 in metastatic ovarian and endometrial cancers, indicating inherent chemotherapy resistance and limited treatment options for patients with these biomarkers.
Lunresertib is also being evaluated in combination with Debio 0123, a WEE1 inhibitor, in Module 4 of the MYTHIC trial, targeting advanced solid tumors with CCNE1 amplification or FBXW7 or PPP2R1A alterations. Initial data from this module is expected in 2025.
Camonsertib (RP-3500) Clinical Updates
Camonsertib, a potential best-in-class oral ATR inhibitor, is being evaluated as a monotherapy in the Phase 2 TRESR clinical trial's non-small cell lung cancer (NSCLC) expansion. Early data suggests a promising signal of prolonged progression-free survival in patients with ATM-mutated NSCLC. Initial data from the TRESR clinical trial is anticipated in 2025.
Phase 1 data from a trial conducted with Memorial Sloan Kettering Cancer Center, presented at the ASTRO annual meeting, highlighted the benefits of camonsertib in combination with palliative radiation for metastatic tumors harboring an ataxia-telangiectasia-mutated (ATM) mutation. The data indicated a higher clinical benefit in patients with pathogenic ATM mutations compared to those with variants of unknown significance.
RP-1664 and RP-3467 Development
RP-1664, a first-in-class, oral, selective PLK4 inhibitor, is being evaluated as a monotherapy in the Phase 1 LIONS clinical trial in adult and adolescent patients with TRIM37-high solid tumors. The company expects to advance RP-1664 into a Phase 1/2 trial in pediatric patients with high-risk, recurrent neuroblastoma.
The first patient has been dosed in the POLAR clinical trial evaluating RP-3467, a Polθ ATPase inhibitor, alone and in combination with the PARP inhibitor, olaparib, in molecularly selected advanced solid tumors, including ovarian, breast, prostate, and pancreatic cancers.
Financial Position
As of September 30, 2024, Repare Therapeutics reported cash, cash equivalents, and marketable securities of $179.4 million, which the company believes is sufficient to fund its operational plans into the second half of 2026.
