Overview
Repare Therapeutics Inc., a leading clinical-stage precision oncology company, presented updated data highlighting the benefits of its individualized schedule for the management of anaemia 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).
MYTHIC Clinical Trial Outcomes
- Lunre+camo in the MYTHIC clinical trial (NCT04855656) previously demonstrated promising clinical activity in molecularly selected patients across multiple tumour 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 anaemia while maintaining clinical benefit.
- Further, Repare observed no thrombocytopenia of any grade nor serious neutropenia in these patients.
Data presentation at 36th EORTC-NCI-AACR (ENA) Symposium, Spain
Dr. Martin Højgaard of Rigshospitalet, Denmark presented this data in a poster titled, “Individualized schedule improves rates and severity of anaemia 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 (ENA) Symposium on Molecular Targets and Cancer Therapeutics, being held October 23-25, 2024 in Barcelona, Spain.
Words from CMO: Repare
- 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 anaemia,” said Maria Koehler, MD, PhD, executive vice president and chief medical officer of Repare.
- We believe that these data demonstrate a favourable and differentiated tolerability profile versus both current and emerging therapies. We look forward to sharing efficacy data from the gynaecological cancer expansion cohort of the MYTHIC clinical trial in December 2024.
Key Clinical Trial Findings:
The individualized schedule mitigated mechanism-based anaemia 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.
Impact of dose optimization
Dose optimization meaningfully reduced Grade 3 anaemia (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 haemoglobin, prior therapies, and treatment intensity (weekly vs. 2 weeks on / 1 week off) predicted Grade 3 anaemia frequency with lunre+camo;
- Anemia reduction was greatest in patients with baseline hemoglobin less than 11g/dL (Grade 3 anaemia 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.
About the Compnay
Repare Therapeutics is a leading clinical-stage precision oncology company enabled by its proprietary synthetic lethality approach to the discovery and development of novel therapeutics.
