Repare Therapeutics Presented Updated Data Highlighting The Benefits Of Its Individualized Schedule For Managing Anemia In Phase 1 MYTHIC Trial, Which Treated Patients With The Combination Of Lunresertib And Camonsertib
Repare Therapeutics Presented Updated Data Highlighting The Benefits Of Its Individualized Schedule For Managing Anemia In Phase 1 MYTHIC Trial, Which Treated Patients With The Combination Of Lunresertib And Camonsertib
Repare Therapeutics展示了更新的数据,突出了其个性化方案治疗贫血的好处,在第1阶段MYTHIC试验中,该试验使用Lunresertib和Camonsertib的联合治疗患者。
Key Clinical Trial Findings:
主要临床试验发现:
- 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.
- 根据在少数患者中观察到的进入血红蛋白,个性化计划缓解了基于机制的贫血
- 时间表变更后,总体临床益处得以维持,放射回归和分子反应总体保持不变:
-尽管时间表发生了变化,但一些患者的靶病变消退程度有所加深
-治疗9周后,对于开始治疗或改用2周/休假1周的患者,未观察到对无进展存活率(PFS)的影响 - 剂量优化显著降低了所有患者的3级贫血(22.6%,之前为51.4%):
-与接受治疗相比,基线骨髓功能是3级贫血的关键原因
-基线血红蛋白、先前的治疗和治疗强度(每周与休息 2 周/休息 1 周的对比)预测的 3 级贫血频率(月经+迷彩)
-基线血红蛋白低于 11g/dL 的患者的贫血减少幅度最大(第 12 周的 3 级贫血:34%,之前为 68%;总体风险降低:58%)
-新的时间表也减少了红细胞输血(13%对比之前的43%)、剂量中断(13%对23%)和剂量减少(6%对17%)
-其他三级事件已经不常见(发生率