FDA Fast Tracks Lunresertib/Camonsertib in Platinum-Resistant Ovarian Cancer

• The FDA granted fast track designation to lunresertib (RP-6306) with camonsertib (RP-3500) for treating adult patients with platinum-resistant ovarian cancer harboring CCNE1 amplifications, FBXW7 mutations, or PPP2R1A mutations, aiming to expedite the development of this treatment.

• The combination therapy is currently being evaluated in the phase 1 MYTHIC study (NCT04855656)

• Data from dose-expansion cohorts of the study are expected in Q4 2024.
  

The FDA has granted a fast track drug designation to the combination of lunresertib with camonsertib for the treatment of adult patients with platinum-resistant ovarian cancer with CCNE1 amplifications, FBXW7 mutations, or PPP2R1A mutations.¹

The combination of lunresertib, a first-in-class, oral, small molecule PKMYT1 inhibitor, and camonsertib, a potential leading ATR inhibitor, is currently being evaluated in the phase 1 MYTHIC study. Alone and in combination with camonsertib, lunresertib has demonstrated safety, tolerability, and early efficacy in this study.

“The FDA’s decision to grant fast track designation supports our goal of quickly and efficiently developing the lunresertib-camonsertib combination for patients with genomically defined platinum-resistant ovarian cancer,” said Maria Koehler, MD, PhD, executive vice president and chief medical officer of Repare Therapeutics, in a press release. “[Patients with] ovarian cancer need therapies that provide long-term benefit beyond that observed with standard of care. Our precision medicine approach targets treatment to patients who could most benefit from a well-tolerated alternative to chemotherapy.”

Previously in 2023, the FDA granted the combination a fast track designation for the treatment of patients with CCNE1-amplified, FBXW7-mutated, or PPP2R1A-mutated endometrial cancer.

About the MYTHIC Trial

MYTHIC is an ongoing, multicenter, open-label, dose-escalation and -expansion, phase 1 trial assessing treatment with lunresertib alone or in combination with camonsertib or Debio 0123, an oral WEE1 inhibitor, for the treatment of patients with advanced solid tumors.²

Patients aged 12 years and older are eligible for enrollment in the study if they have locally advanced or metastatic resistant or refractory solid tumors. Those under the age of 18 must weigh at least 40 kg. Additional criteria require patients to have tumors that harbor CCNE1 amplifications per a tumor or plasma next-generation sequencing (NGS) test or fluorescence in situ hybridization, FBXW7 deleterious mutations per a tumor or plasma NGS test, or PPP2R1A deleterious mutations per a tumor or plasma NGS test. Patients must also have a Lansky performance status of at least 50% if aged 16 years of age and younger, and for those over 16, patients must have an ECOG performance status of 0 or 1 (or 2 for module 1). Further, patients are required to have measurable disease per RECIST 1.1 criteria and adequate hematologic and organ function.

Once enrolled in the study, patients will be treated with lunresertib alone, lunresertib in combination with camonsertib, or lunresertib in combination with Debio 0123. Patients will continue treatment until disease progression, unacceptable toxicity, or investigator/patient decision.

Safety and tolerability are the primary end points of the study and include defining the maximum tolerated dose and recommended phase 2 dose of lunresertib alone, lunresertib with camonsertib, and lunresertib with Debio 0123. Investigators are also evaluating pharmacokinetics (PK).
Secondary end points of the study include evaluating the preliminary antitumor activity of the 3 regimens, plasma concentrations of lunresertib monotherapy, the relationship between pharmacodynamic biomarkers and PK of lunresertib at different dose levels and schedules, and plasma concentrations for the combination.

Data from module 2 of the MYTHIC study, which includes dose-expansion cohorts with approximately 20 to 30 patients with ovarian or endometrial cancer enrolled, are expected to be read out in the fourth quarter of 2024.¹

REFERENCES:
1. Repare Therapeutics announces fast track designation granted by the FDA for lunresertib in combination with camonsertib for the treatment of platinum-resistant ovarian cancer. News release. Repare Therapeutics. June 4, 2024. Accessed June 6, 2024. https://tinyurl.com/5d84r4ts
2. Study of RP-6306 alone or in combination with RP-3500 or Debio 0123 in patients with advanced solid tumors (MYTHIC). ClinicalTrials.gov. Updated April 15, 2024. Accessed June 6, 2024. https://clinicaltrials.gov/study/NCT04855656