On October 23, 2024 Repare Therapeutics Inc. ("Repare" or the "Company") (Nasdaq: RPTX), a leading clinical-stage precision oncology company, reported updated data highlighting the benefits of its individualized schedule for the management of anemia in the Phase 1 MYTHIC clinical trial treating patients with the combination of lunresertib, a first-in-class PKMYT1 inhibitor, and camonsertib, a potential best-in-class oral small molecule ATR inhibitor (lunre+camo) (Press release, Repare Therapeutics, OCT 23, 2024, View Source [SID1234647356]).

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Lunre+camo in the MYTHIC clinical trial (NCT04855656) previously demonstrated promising clinical activity in molecularly selected patients across multiple tumor types. In this analysis, Repare followed patients for approximately nine months at the recommended Phase 2 dose (RP2D) to assess the effectiveness of an individualized schedule. The analysis demonstrated a successful approach to mitigating mechanism-based anemia while maintaining clinical benefit. Further, Repare observed no thrombocytopenia of any grade nor serious neutropenia in these patients.

Dr. Martin Højgaard of Rigshospitalet, Denmark presented this data in a poster titled, "Individualized schedule improves rates and severity of anemia in patients treated with lunresertib, a PKMYT1 inhibitor, and camonsertib, an ATR inhibitor, in the Phase I MYTHIC study (NCT04855656)" at the 36th EORTC-NCI-AACR (Free EORTC-NCI-AACR Whitepaper) (ENA) Symposium on Molecular Targets and Cancer Therapeutics, being held October 23-25, 2024 in Barcelona, Spain.

"This individualized schedule in heavily pretreated patients with advanced cancers from our MYTHIC clinical trial met its goal of maintaining antitumor activity while reducing rates of grade 3 anemia," said Maria Koehler, MD, PhD, Executive Vice President and Chief Medical Officer of Repare. "We believe that these data demonstrate a favorable and differentiated tolerability profile versus both current and emerging therapies. We look forward to sharing efficacy data from the gynecological cancer expansion cohort of the MYTHIC clinical trial in December 2024."

Key Clinical Trial Findings:

The individualized schedule mitigated mechanism-based anemia based on entry hemoglobin observed in a minority of patients
Overall clinical benefit was maintained after schedule change with generally maintained radiographic regressions and molecular responses:
– Despite the change in schedule, deepening of target lesion regression was noted in some patients
– After 9 weeks on therapy, there was no observed impact on Progression Free Survival (PFS) in patients who started on or switched to the schedule of 2 weeks on / 1 week off of treatment
Dose optimization meaningfully reduced Grade 3 anemia (22.6% vs. 51.4%, previously) in all patients:
– Baseline marrow function was the key reason for Grade 3 anemia as opposed to exposure to therapy
– Baseline hemoglobin, prior therapies, and treatment intensity (weekly vs. 2 weeks on / 1 week off) predicted Grade 3 anemia frequency with lunre+camo
– Anemia reduction was greatest in patients with baseline hemoglobin less than 11g/dL (Grade 3 anemia at week 12: 34% vs. 68%, previously; overall risk reduction: 58%)
– Red blood cell transfusions (13% vs. 43%, previously), dose interruptions (13% vs. 23%) and dose reductions (6% vs. 17%) were also reduced with the new schedule
– Other Grade 3 events were already uncommon (<5% incidence) and remained consistently low, regardless of schedule