ORIC Pharmaceuticals starts Phase 3 Himalayas-1 trial in mCRPC
ORIC Pharmaceuticals has initiated the Himalayas-1 global Phase 3 registrational trial, evaluating its EED inhibitor rinzimetostat in combination with darolutamide in patients with metastatic castration-resistant prostate cancer (mCRPC) who have previously received abiraterone. The announcement, made on 14 July 2026, also confirmed a clinical trial collaboration and supply agreement with Bayer AG, under which Bayer will provide its approved AR inhibitor NUBEQA (darolutamide) at no cost for use in the study.
The trial's initiation follows End-of-Phase 1 interactions with the FDA and other global health authorities, and builds on earlier dose-optimisation work that identified 400 mg once daily as the recommended Phase 3 dose for rinzimetostat. ORIC retains full global development and commercial rights to the drug; the Bayer agreement grants no licence or option over rinzimetostat.
Trial design and endpoints
Himalayas-1 will enrol approximately 600 patients across more than 250 sites in 25 countries, randomised 1:1. The experimental arm receives 400 mg once daily rinzimetostat combined with darolutamide; the comparator arm receives physician's choice of an AR inhibitor or docetaxel. The primary endpoint is radiographic progression-free survival, with overall survival as the key secondary endpoint. Additional secondary endpoints include PSA response rate, objective response rate, and patient-reported outcomes. The breadth of the comparator arm reflects current real-world practice variation in post-abiraterone mCRPC and should support a broad label if results are positive.
Jacob Chacko, president and chief executive of ORIC, said the Phase 3 initiation "represents an important milestone toward establishing rinzimetostat as a potentially practice-changing therapy for patients," noting the collaboration with Bayer "underscores our shared interest in evaluating this regimen."
Market context and competitive landscape
The post-abiraterone mCRPC setting is one of the most contested spaces in prostate cancer drug development. Patients who progress on abiraterone face a narrowing set of options with meaningful efficacy, and the optimal sequencing of AR-pathway agents, taxanes, and newer targeted approaches remains actively debated. Rinzimetostat's mechanism, allosteric inhibition of the polycomb repressive complex 2 via its EED subunit, is designed to counteract epigenetic resistance that can develop following AR-directed therapy. This differentiates it mechanistically from most approved agents in the indication, though clinical differentiation will need to be demonstrated in the Phase 3 dataset.
The broader PRC2 inhibitor class has had a mixed clinical history. Tazemetostat, an EZH2 inhibitor that targets a different subunit of PRC2, is approved in follicular lymphoma and epithelioid sarcoma but has not advanced in prostate cancer. ORIC's EED-targeting approach is therefore less clinically validated at the mechanistic level, making the Himalayas-1 read-out especially significant for the class as a whole.
For Bayer, the supply agreement is a relatively low-risk means of gathering additional real-world combination data on darolutamide, whose label is currently anchored to non-metastatic CRPC and earlier metastatic disease. A positive Himalayas-1 outcome could support a label extension conversation, even though Bayer holds no formal rights in the deal.
The trial's size, geographic footprint, and clearly defined endpoints position ORIC for a clean regulatory interaction if efficacy signals hold. Investors will be watching enrolment pace, given the competitive landscape for mCRPC patients eligible for post-abiraterone studies, and any interim data updates that may emerge ahead of primary completion.