Repare Therapeutics Inc. (Nasdaq: RPTX), a clinical-stage precision oncology company, today announced positive data from its MYTHIC Phase 1 gynecologic expansion clinical trial. The trial evaluated the combination of lunresertib and camonsertib (Lunre+Camo) at the recommended Phase 2 dose (RP2D) in patients with endometrial cancer and platinum-resistant ovarian cancer (PROC) that exhibit lunre-sensitizing biomarkers.
Lunresertib is a first-in-class small molecule PKMYT1 inhibitor, targeting cell cycle regulation in Lunre BM+ tumors, which include those with CCNE1 amplifications or FBXW7 or PPP2R1A mutations. Camonsertib is a potential best-in-class ATR inhibitor that targets the DNA damage response pathway.
Lloyd M. Segal, President and CEO of Repare, commented, “We are encouraged by the strong response and clear benefit observed in patients with endometrial and platinum-resistant ovarian cancers in the MYTHIC clinical trial. These patients need new treatments, and our results support the potential of Lunre+Camo to make a significant difference, especially as an alternative to chemotherapy. We have received positive feedback from regulatory agencies in both the U.S. and Europe, and we look forward to initiating a Phase 3 trial in endometrial cancer in the second half of 2025.”
The MYTHIC trial (NCT04855656) is a global, open-label Phase 1 study designed to evaluate the safety, pharmacokinetics, pharmacodynamics, and early anti-tumor activity of Lunre+Camo in advanced solid tumors. As of November 14, 2024, 51 evaluable patients were enrolled in the gynecologic cancer cohort.
Across all treated tumor types at the optimized RP2D (n=67), Lunre+Camo showed a favorable and differentiated tolerability profile compared to existing therapies, with anemia being the most common adverse event (26.9%, Grade 3).
Endometrial Cancer Findings:
- 27 evaluable patients with a median age of 67 years.
- 100% had prior platinum therapy, and 77.8% had received immune checkpoint inhibitors.
- 56% had PPP2R1A mutations; 22% had FBXW7 mutations; 15% had CCNE1 amplification.
- Key efficacy outcomes:
- Overall response rate (ORR) of 25.9% (confirmed ORR in 5 out of 7 patients).
- Clinical benefit observed in 48.1% of patients.
- At 24 weeks, 43% of patients showed durable clinical benefit (PFS24w).
Platinum-Resistant Ovarian Cancer Findings:
- 24 evaluable patients with a median age of 63 years.
- 100% were platinum-resistant or ineligible, with 45.8% having prior PARP inhibitors and 70.8% having received prior bevacizumab.
- 87.5% of tumors had CCNE1 amplification.
- Key efficacy outcomes:
- ORR of 37.5% (confirmed ORR in 4 out of 9 patients).
- Clinical benefit observed in 79% of patients.
- PFS24w of 45%.
Brian Slomovitz, MD, MS, FACOG, Director of Gynecologic Oncology at Mount Sinai Medical Center, stated, “Repare’s biomarker-driven approach addresses the urgent need for new treatment options for recurrent gynecologic cancers. The data support the potential of Lunre+Camo as a new treatment option for endometrial and platinum-resistant ovarian cancers.”
Repare has consulted with the U.S. FDA and the European Medicines Agency, receiving guidance on the registrational development plans for Lunre+Camo in gynecologic cancers. The company plans to submit final Phase 3 trial protocols for regulatory clearance soon and expects to begin the Phase 3 trial for endometrial cancer in the second half of 2025. Additionally, Repare intends to start a small contribution of components trial in endometrial cancer in early 2025.
Maria Koehler, MD, PhD, Chief Medical Officer of Repare, added, “The results from the MYTHIC trial increase our confidence in the potential of Lunre+Camo to offer a new treatment option for patients with aggressive recurrent endometrial cancer. We are grateful to all those involved in the trial and look forward to advancing these promising data.”
About Repare Therapeutics Inc. Repare Therapeutics is a clinical-stage precision oncology company focused on developing novel therapeutics using a synthetic lethality approach. The company’s pipeline includes lunresertib (RP-6306), camonsertib (RP-3500), and other therapies targeting genomic instability and DNA damage repair. Repare uses its SNIPRx® platform to identify highly targeted cancer therapies.