ORIC selects 400 mg RP3D of rinzimetostat, shows 84% five-month rPFS
ORIC Pharmaceuticals selected 400 mg once-daily rinzimetostat in combination with darolutamide as the RP3D for its Himalayas-1 Phase 3 mCRPC trial starting 1H 2026. In Phase 1b, 400 mg dosing achieved an 84% five-month rPFS with mostly Grade 1-2 adverse events (fatigue 39%, diarrhea 22%, nausea 22%) and minimal dose modifications.
1. RP3D Selection for Phase 3 Trial
ORIC conducted an exposure-response analysis across over 100 patients, comparing 400 mg and 600 mg once-daily dosing of rinzimetostat with darolutamide. Both doses delivered similar efficacy, but the 600 mg arm showed higher toxicity and more treatment modifications, leading to selection of 400 mg as the recommended Phase 3 dose.
2. Phase 1b Safety and Tolerability Data
In the Phase 1b cohort, 400 mg once-daily rinzimetostat exhibited a highly differentiated safety profile, with 39% of patients reporting fatigue (17% Grade 1, 22% Grade 2), 22% diarrhea, and 22% nausea, all mostly Grade 1-2. Only one Grade 3 treatment-related event occurred, with one treatment interruption and no dose reductions required.
3. Preliminary Efficacy Outcomes
Among 18 efficacy-evaluable mCRPC patients with a median follow-up of 4.9 months, landmark radiographic progression-free survival rates were 93% at three months, and 84% at both four and five months. Additional analyses showed 47% of patients achieved a PSA50 response and 71% experienced over 50% ctDNA reduction.
4. Himalayas-1 Phase 3 Trial Plans
ORIC plans to initiate the global Himalayas-1 registrational trial in the first half of 2026, enrolling approximately 600 post-abiraterone mCRPC patients across more than 250 sites. The study will evaluate the efficacy and safety of 400 mg once-daily rinzimetostat plus standard-dose darolutamide.