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A Study to Learn About the Investigational Drug Rinzimetostat (ORIC-944) in Patients With mCRPC Who Were Previously Treated With Abiraterone Acetate (Himalayas-1) (Himalayas-1)

2 septembre 2026 mis à jour par: ORIC Pharmaceuticals

A Phase 3, Randomized, Open-Label Study of Rinzimetostat (ORIC-944) in Combination With Darolutamide Compared With ARPI or Docetaxel in Patients With Metastatic Castration Resistant Prostate Cancer Previously Treated With Abiraterone Acetate (Himalayas-1)

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.

Aperçu de l'étude

Statut

Recrutement

Les conditions

Intervention / Traitement

Type d'étude

Interventionnel

Inscription (Estimé)

600

Phase

  • Phase 3

Contacts et emplacements

Cette section fournit les coordonnées de ceux qui mènent l'étude et des informations sur le lieu où cette étude est menée.

Coordonnées de l'étude

Lieux d'étude

  • États-Unis
    • Indiana
      • Jeffersonville, Indiana, États-Unis, 40207
        • Recrutement
        • First Urology PSC
    • North Carolina
      • Charlotte, North Carolina, États-Unis, 29464
        • Recrutement
        • Urology Specialists of the Carolinas - University Place
        • Chercheur principal:
          • Jeremy Hubbard, MD
    • Ohio
      • Canton, Ohio, États-Unis, 44718
        • Recrutement
        • Gabrail Cancer Center Research
    • Texas
      • Dallas, Texas, États-Unis, 75231
        • Recrutement
        • Urology Clinics of North Texas
      • Fort Worth, Texas, États-Unis, 76132
        • Recrutement
        • Urology Partners of North Texas (UPNT)
      • Houston, Texas, États-Unis, 77027
        • Recrutement
        • Houston Metro Urology (HMU)
    • Utah
      • Murray, Utah, États-Unis, 84107
        • Recrutement
        • Summit Urology
        • Chercheur principal:
          • Stewart Landau, MD

Critères de participation

Les chercheurs recherchent des personnes qui correspondent à une certaine description, appelée critères d'éligibilité. Certains exemples de ces critères sont l'état de santé général d'une personne ou des traitements antérieurs.

Critère d'éligibilité

Âges éligibles pour étudier

  • Adulte
  • Adulte plus âgé

Accepte les volontaires sains

Non

La description

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

Plan d'étude

Cette section fournit des détails sur le plan d'étude, y compris la façon dont l'étude est conçue et ce que l'étude mesure.

Comment l'étude est-elle conçue ?

Détails de conception

  • Objectif principal: Traitement
  • Répartition: Randomisé
  • Modèle interventionnel: Affectation parallèle
  • Masquage: Aucun (étiquette ouverte)

Armes et Interventions

Groupe de participants / Bras
Intervention / Traitement
Comparateur actif: Investigational Arm
Rinzimetostat + darolutamide
Médicament: Rinzimetostat
400 mg once daily (QD)
Autres noms:
  • ORIC-944
Médicament: Darolutamide
600 mg twice daily (BID)
Autres noms:
  • Nubeqa
Comparateur actif: Physician's Choice
Control Arm
Médicament: Darolutamide
600 mg twice daily (BID)
Autres noms:
  • Nubeqa
Médicament: Enzalutamide
160 mg once daily (QD)
Autres noms:
  • Xtandi
Médicament: Docetaxel
75 mg/m2 intravenously (IV) every 21 days for up to 10 cycles
Autres noms:
  • Taxotère

Que mesure l'étude ?

Principaux critères de jugement

Mesure des résultats
Description de la mesure
Délai
Radiographic Progression Free Survival assessed by blinded independent central review (BICR) per RECIST v1.1 and Prostate Cancer Clinical Trials Working Group 3 (PCWG3)
Délai: Randomization up to ~2 years
Radiographic Progression Free Survival is defined as the time from the date of randomization to first evidence of radiographic progression as assessed in soft tissue by RECIST 1.1 or in bone per PCWG3 guideline by BICR, or death, whichever occurs first
Randomization up to ~2 years

Mesures de résultats secondaires

Mesure des résultats
Description de la mesure
Délai
Overall Survival (OS)
Délai: 5 years
OS is defined as time from date of randomization to date of death due to any cause
5 years
Objective response rate (ORR)
Délai: Randomization up to ~2 years
ORR is defined as proportion of patients with measurable soft tissue disease at baseline who have a confirmed objective response of complete response (CR) or partial response (PR)
Randomization up to ~2 years
Duration of Response (DoR)
Délai: Randomization up to ~2 years
DOR is defined as time of first response to first documentation of radiographic progression or death, whichever occurs first
Randomization up to ~2 years
Prostate Specific Antigen (PSA) response
Délai: Randomization up to ~2 years
Defined as the proportion of patients with a confirmed ≥50% and ≥90% decline in PSA from baseline as per the PCWG3 criteria, along with the maximum decline in PSA occurring at any point on study
Randomization up to ~2 years
Time to PSA progression
Délai: Randomization up to ~2 years
Measured from the start of treatment until criteria for PSA progression are met as per PCWG3
Randomization up to ~2 years
Time to initiation of antineoplastic therapy
Délai: Randomization up to ~4 years
Time from randomization to first symptomatic skeletal event (symptomatic bone fractures, spinal cord compression, surgery or radiation to the bone whichever is first)
Randomization up to ~4 years
Time to first symptomatic skeletal event
Délai: Randomization up to ~4 years
Time from randomization to first symptomatic skeletal event (symptomatic bone fractures, spinal cord compression, surgery or radiation to the bone whichever is first) Compare patient reported outcomes (PROs) between the investigational treatment and control arms
Randomization up to ~4 years
Change from baseline in patient reported pain symptoms per Brief Pain Inventory-Short Form (BPI-SF)
Délai: Randomization up to ~4 years
Analysis of Brief Pain Inventory-Short Form (BPI-SF) will be based on the pain severity score (mean of individual BPI-SF items 3, 4, 5 and 6), the pain interference score (the mean of items 9A-9G), and the single BPI-SF Item 3 which asks the patient to rate pain at its worst in the last 24 hours
Randomization up to ~4 years
Change from baseline in health-related quality of life (HRQoL) per Functional Assessment of Cancer Therapy - Prostate (FACT-P)
Délai: Randomization up to ~4 years
Change from baseline in HRQoL (FACT-P total score) will be presented. The FACT-P total score will be calculated based on the participant responses to the 39 items in the FACT-P questionnaire. Each item is rated on a 0 to 4 Likert-type scale and then combined to produce the FACT-P total score (0-156), with higher scores representing better health-related quality of life
Randomization up to ~4 years
Change from baseline in social/family well-being per Functional Assessment of Cancer Therapy - Prostate (FACT-P)
Délai: Randomization up to ~4 years
Change from baseline in social/family well-being score will be presented. The social/family well-being score will be calculated based on 7 items in the FACT-P questionnaire; score range 0-28. Each item is rated on a 0 to 4 Likert-type scale
Randomization up to ~4 years
Change from baseline in functioning well-being per Functional Assessment of Cancer Therapy - Prostate (FACT-P)
Délai: Randomization up to ~4 years
Change from baseline in functioning well-being score will be presented. The functioning well-being score will be calculated based on 7 items in the FACT-P questionnaire; score range 0-28. Each item is rated on a 0 to 4 Likert-type scale
Randomization up to ~4 years
Change from baseline in physical well-being per Functional Assessment of Cancer Therapy - Prostate (FACT-P)
Délai: Randomization up to ~4 years
Change from baseline in physical well-being score will be presented. The physical well-being score will be calculated based on 7 items in the FACT-P questionnaire; score range 0-28. Each item is rated on a 0 to 4 Likert-type scale
Randomization up to ~4 years
Change from baseline in symptoms per Functional Assessment of Cancer Therapy - Prostate (FACT-P)
Délai: Randomization up to ~4 years
Change from baseline prostate cancer symptoms (PCS) score will be presented. The PCS score will be calculated based on 12 items in the FACT-P questionnaire; score range 0-48. Each item is rated on a 0 to 4 Likert-type scale
Randomization up to ~4 years
Change from baseline in patient reported health status per European Quality of Life 5-Dimension 5 Level (EQ-5D-5L)
Délai: Randomization up to ~4 years
Participants will self-rate their current state of mobility, self-care, usual activities, pain/discomfort, and anxiety/depression by choosing 1 of 5 possible responses that record the level of severity (no problems, slight problems, moderate problems, severe problems, or extreme problems) within each dimension. The questionnaire also includes a visual analog scale to self-rate general health state on a scale from "the worst health you can imagine" to "the best health you can imagine."
Randomization up to ~4 years
Symptomatic toxicity as measured by items from the Patient-Reported Outcome CTCAE (PRO-CTCAE)
Délai: Randomization up to ~2 years
Each selected PRO-CTCAE items will be assessed related to one or more attributes that include counts for the frequency, severity, and/or interference with usual or daily activities
Randomization up to ~2 years
Overall side effect burden as measured by the FACT- GP5
Délai: Randomization up to ~2 years
The FACT-GP5 question assesses overall side effect burden with the following response options "I am bothered by side effects of treatment," is rated on a 5-point scale ranging from "not at all" (0) to "very much" (4) and counts will be presented
Randomization up to ~2 years
Time to confirmatory deterioration in patient-reported pain symptoms per BPI-SF Item 3 "worst pain in 24 hours"
Délai: Randomization up to ~4 years
Defined as the time from randomization to onset of pain progression, which is defined as > 2-point increase from baseline in the score from the BPI-SF Question 3 that is confirmed at the next consecutive assessment > 4 weeks apart or an initial deterioration followed by death before the next assessment
Randomization up to ~4 years
Time to definitive deterioration in patient-reported health related quality of life (HRQoL) per FACT-P
Délai: Randomization up to ~4 years
Defined as the time from randomization to onset of definitive deterioration in FACT-P total score, which is defined as >10 point decrease from baseline and no subsequent observations with a <10 point decrease from baseline FACT-P total score
Randomization up to ~4 years
Time to definitive deterioration in patient-reported physical well-being per FACT-P
Délai: Randomization up to ~4 years
Time to definitive deterioration in physical well-being (PWB) per FACT-P is defined as the time from randomization to onset of definitive deterioration in physical well-being, which is defined as ≥3-point
Randomization up to ~4 years
Incidence of Adverse Events (AEs)
Délai: Randomization up to ~2 years
Type, incidence, relationship to study treatments, severity, and seriousness of AEs [as graded by National Cancer Institute (NCI) common terminology criteria for adverse events (CTCAE) v6.0] and other clinical assessments
Randomization up to ~2 years
Evaluate the pharmacokinetics (PK) of rinzimetostat in combination with darolutamide
Délai: Randomization up to ~1 year
Rinzimetostat characterized by predose and postdose plasma concentrations at selected time points
Randomization up to ~1 year

Collaborateurs et enquêteurs

C'est ici que vous trouverez les personnes et les organisations impliquées dans cette étude.

Parrainer

ORIC Pharmaceuticals

Collaborateurs

Bayer

Dates d'enregistrement des études

Ces dates suivent la progression des dossiers d'étude et des soumissions de résultats sommaires à ClinicalTrials.gov. Les dossiers d'étude et les résultats rapportés sont examinés par la Bibliothèque nationale de médecine (NLM) pour s'assurer qu'ils répondent à des normes de contrôle de qualité spécifiques avant d'être publiés sur le site Web public.

Dates principales de l'étude

Début de l'étude (Réel)

3 août 2026

Achèvement primaire (Estimé)

1 mars 2028

Achèvement de l'étude (Estimé)

1 septembre 2030

Dates d'inscription aux études

Première soumission

18 juin 2026

Première soumission répondant aux critères de contrôle qualité

20 juillet 2026

Première publication (Réel)

23 juillet 2026

Mises à jour des dossiers d'étude

Dernière mise à jour publiée (Réel)

3 septembre 2026

Dernière mise à jour soumise répondant aux critères de contrôle qualité

2 septembre 2026

Dernière vérification

1 septembre 2026

Plus d'information

Termes liés à cette étude

Mots clés

Termes MeSH pertinents supplémentaires

Autres numéros d'identification d'étude

  • ORIC-944-05
  • 2026-525340-15-00 (Ctis)

Plan pour les données individuelles des participants (IPD)

Prévoyez-vous de partager les données individuelles des participants (DPI) ?

NON

Informations sur les médicaments et les dispositifs, documents d'étude

Étudie un produit pharmaceutique réglementé par la FDA américaine

Oui

Étudie un produit d'appareil réglementé par la FDA américaine

Non

produit fabriqué et exporté des États-Unis.

Non

Ces informations ont été extraites directement du site Web clinicaltrials.gov sans aucune modification. Si vous avez des demandes de modification, de suppression ou de mise à jour des détails de votre étude, veuillez contacter register@clinicaltrials.gov. Dès qu'un changement est mis en œuvre sur clinicaltrials.gov, il sera également mis à jour automatiquement sur notre site Web .

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