Repare Therapeutics Inc. (Nasdaq: RPTX) announced updated positive safety and tolerability results from its Phase 1 MYTHIC clinical trial, evaluating the combination of lunresertib, a PKMYT1 inhibitor, and camonsertib, an ATR inhibitor (lunre+camo). The data, presented at the EORTC-NCI-AACR Symposium, highlighted the benefits of an individualized schedule for managing anemia in patients treated with the combination therapy.
The MYTHIC trial (NCT04855656) has previously shown promising clinical activity in molecularly selected patients across various tumor types. In this analysis, patients were followed for approximately nine months at the recommended Phase 2 dose (RP2D) to assess the effectiveness of the individualized schedule. The results demonstrated a successful approach to mitigating mechanism-based anemia while maintaining clinical benefit. Notably, no thrombocytopenia of any grade nor serious neutropenia was observed in these patients.
Individualized Schedule Improves Anemia Rates
Dr. Martin Højgaard of Rigshospitalet, Denmark, presented the data, which focused on how an individualized schedule improves rates and severity of anemia in patients treated with lunresertib and camonsertib. The key finding was that the individualized schedule effectively mitigated mechanism-based anemia, which is often observed with these types of inhibitors.
Maria Koehler, MD, PhD, Executive Vice President and Chief Medical Officer of Repare, stated, "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." She added, "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 updated data revealed several 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 the schedule change, with generally maintained radiographic regressions and molecular responses. Deepening of target lesion regression was noted in some patients despite the change in schedule.
- 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 identified as 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.
