ORIC initiates the global Phase 3 Himalayas-1 trial evaluating rinzimetostat plus NUBEQA (darolutamide) for metastatic castration-resistant prostate cancer after abiraterone.
Written By: Anshu Gupta, PharmD
Reviewed By: Pharmacally Editorial Team
ORIC Pharmaceuticals has announced the initiation of the Himalayas-1 global Phase 3 registrational trial evaluating rinzimetostat in combination with NUBEQA® (darolutamide) for patients with metastatic castration-resistant prostate cancer (mCRPC) whose disease has progressed following treatment with abiraterone. The study is being conducted under a clinical trial collaboration with Bayer, which will supply darolutamide for use in the study.
Patients with mCRPC who experience disease progression after abiraterone continue to represent a population with substantial unmet medical need. According to ORIC, rinzimetostat has continued to demonstrate a potential best-in-disease clinical profile in earlier clinical development, supporting its advancement into the Phase 3 registrational study. Dr. Jacob M. Chacko, Chief Executive Officer of ORIC Pharmaceuticals, noted that patients whose disease progresses after abiraterone continue to have limited treatment options, highlighting the need for new therapeutic approaches.
The initiation of Himalayas-1 follows ORIC’s previously presented dose optimization data for rinzimetostat. The company identified 400 mg once daily as the recommended Phase 3 dose (RP3D). Following End-of-Phase 1 interactions with the U.S. Food and Drug Administration and other global health authorities, ORIC finalized the Phase 3 protocol and initiated the Himalayas-1 registrational trial.
Trial Design
Himalayas-1 is a global Phase 3 registrational trial expected to enroll approximately 600 patients across more than 250 clinical sites in 25 countries. Eligible participants are patients with mCRPC who have previously been treated with abiraterone and have experienced disease progression.
Participants will be randomized 1:1 to receive either the investigational combination or physician’s choice of standard therapy. The investigational treatment arm will receive rinzimetostat 400 mg once daily in combination with darolutamide. The control arm will receive physician’s choice of an androgen receptor (AR) inhibitor or docetaxel, consistent with the study protocol.
Study Endpoints
The primary endpoint of the trial is radiographic progression-free survival (rPFS). The key secondary endpoint is overall survival (OS). Additional secondary endpoints include PSA response rate, objective response rate (ORR), and patient-reported outcomes (PROs). These secondary endpoints will further evaluate antitumor activity and the impact of treatment on patients’ quality of life.
Bayer Collaboration
Under the clinical trial collaboration and supply agreement, ORIC will sponsor and conduct the Himalayas-1 trial. Bayer will provide NUBEQA® (darolutamide) at no cost for use in the trial in combination with rinzimetostat. The agreement does not grant Bayer any license, option, or other rights to rinzimetostat, while ORIC retains full worldwide development and commercialization rights to the investigational therapy.
Clinical Significance
In the announcement, Dr. Jacob M. Chacko said that patients with mCRPC who progress after abiraterone continue to have significant unmet medical needs and limited treatment options. He stated that the initiation of the Himalayas-1 Phase 3 trial represents an important milestone toward evaluating rinzimetostat as a potential new treatment option for these patients. He also noted that the collaboration with Bayer strengthens ORIC’s global operational readiness by securing access to darolutamide for the Phase 3 study, supporting the advancement of the investigational combination.
What This Means to Patient
The Himalayas-1 trial is designed to evaluate whether the combination of rinzimetostat and NUBEQA® (darolutamide) can improve radiographic progression-free survival compared with currently available treatment options in patients with mCRPC previously treated with abiraterone. Overall survival and additional secondary endpoints will provide further evidence regarding the regimen’s clinical benefit and patient experience. As stated in the announcement, the combination remains investigational, and the results of the Phase 3 trial will determine its potential role in the treatment of this patient population.
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About the Writer
Anshu Gupta(LinkedIn) is a PharmD professional and healthcare writer with interests in clinical research, pharmacovigilance, regulatory affairs, and medical writing. She has presented research at academic conferences and completed certifications in Good Clinical Practice (GCP), ICH-GCP, and drug safety. Passionate about clinical trials and evidence-based medicine, she is committed to translating scientific evidence into accurate, reliable, and accessible healthcare content.