Overview

Himalayas-1 is a randomized, open-label, global, multicenter phase 3 study evaluating whether the combination of rinzimetostat with darolutamide is more effective compared to physician's choice of control; ARPI (darolutamide or enzalutamide) or docetaxel for treating patients with metastatic castration resistant prostate cancer (mCRPC) who were previously treated with abiraterone acetate.

The primary objective of this study is to demonstrate superiority in radiographic progression free survival (rPFS) of the investigational arm of rinzimetostat + darolutamide combination versus physician's choice of control: ARPI (darolutamide or enzalutamide) or docetaxel.

Eligibility

Inclusion Criteria:

• Histologically or cytologically confirmed adenocarcinoma of the prostate without small cell features
• Progressive disease in the setting of surgical or medical castration with evidence of disease progression on treatment with abiraterone acetate in the mCSPC setting or first line mCRPC setting is required
• Metastatic disease in bone documented on bone scan, or in soft tissue documented on CT/MRI scan
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
• Adequate organ function

Exclusion Criteria:

• Prior treatment for prostate cancer at any stage with cytotoxic chemotherapy, radioligand therapy (ie, 177Lu -PSMA-617, radium-223), ARPIs including apalutamide, darolutamide, and enzalutamide, PARP monotherapy or other systemic anticancer treatment (approved drugs or experimental compounds such as, antibody therapy, immunotherapy, gene or cell therapy, angiogenesis inhibitors, CDK4/6 inhibitors, PRC2 inhibitors) with the following exceptions:
  1. Treatment with first-generation antiandrogen agents (eg, bicalutamide, flutamide, nilutamide), but must be discontinued prior to the first dose of study medication
  2. Docetaxel treatment is allowed for mCSPC, as long as no signs of failure or disease progression occurred during treatment or within 3 months of treatment completion
• Any other anticancer therapy (drug or vaccine which does not meet exclusion criterion 1 above) within 28 days or 5 half-lives (whichever is longer) prior to randomization
• Known or suspected brain metastasis or active leptomeningeal disease
• Clinically significant cardiovascular disease defined as:
• Any medical (including active or clinically significant bacterial, fungal, or viral infection) or psychiatric condition including recent (within the past year) or active suicidal ideation/behavior or laboratory abnormality that may increase the risk of study participation or, in the investigator's judgment, make the patient inappropriate for the study
• Active inflammatory gastrointestinal disease, chronic diarrhea, or previous gastric resection or lap-band surgery are excluded