Repare Therapeutics has announced positive results from its MYTHIC Phase 1 clinical trial, evaluating the combination of lunresertib and camonsertib (Lunre+Camo) in patients with endometrial cancer and platinum-resistant ovarian cancer. The trial demonstrated promising overall response rates and progression-free survival, supporting plans for a Phase 3 trial in endometrial cancer.
MYTHIC Trial Results
The MYTHIC trial (NCT04855656) is a first-in-human, global, open-label Phase 1 dose-escalation clinical trial. As of the data cut-off date of November 14, 2024, 51 evaluable patients were enrolled in the gynecologic cancer expansion cohort of the MYTHIC trial.
In endometrial cancer patients (n=27), the overall response rate (ORR) was 25.9%, with a clinical benefit observed in 48.1% of patients. At the 24-week landmark analysis, nearly half of patients experienced durable clinical benefit, with a 24-week progression-free survival (PFS) rate of 43% (95% CI, 21-63%).
For platinum-resistant ovarian cancer patients (n=24), the ORR was 37.5%, and clinical benefit was observed in 79% of patients. The PFS at the 24-week landmark analysis was 45% (95% CI, 22-66%).
Across all tumor types treated at the optimized recommended Phase 2 dose (RP2D) (n=67), Lunre+Camo therapy demonstrated a favorable and differentiated tolerability profile when compared to current and emerging therapies. The most common adverse event was anemia (26.9%, Grade 3).
Patient Characteristics
Endometrial cancer patients had a median age of 67 years, with 100% having undergone prior platinum therapy and 77.8% having received immune checkpoint inhibitors. 59% of patients received the combination as a fourth line of therapy or beyond. 85% of tumors had p53 mutations.
Platinum-resistant ovarian cancer patients had a median age of 63 years, with 100% being platinum-resistant or platinum ineligible. 45.8% of patients had received prior PARP inhibitors, and 70.8% had received prior bevacizumab. 54% of patients received the combination as a fourth line of therapy or beyond. 100% of tumors had p53 mutations.
Planned Phase 3 Trial
Repare plans to initiate a registrational Phase 3 Lunre+Camo trial in endometrial cancer in the second half of 2025. The company has consulted with both the U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA), who have provided guidance into the Company’s registrational development plans for Lunre+Camo in gynecologic tumors.
Expert Commentary
"Those patients with recurrent gynecologic cancers have limited treatment options as tumors often become resistant to standard of care therapy," said Brian Slomovitz, MD, MS, FACOG, Director, Gynecologic Oncology, Co-chair of the Cancer Research Center, Mount Sinai Medical Center. "They urgently need new treatment options. Repare’s differentiated, biomarker-driven approach addresses this population and may offer a solution. These data support the potential of Lunre+Camo as a new treatment option to fill this unmet need for patients with endometrial and platinum-resistant ovarian cancers."
About Lunre+Camo
Lunresertib is a first-in-class precision oncology small molecule PKMYT1 inhibitor which targets cell cycle regulation in Lunre BM+ tumors (CCNE1 amplifications or FBXW7 or PPP2R1A deleterious alterations). Camonsertib is a potential best-in-class oral small molecule inhibitor of ATR, a critical component of the DNA damage response pathway.
