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)
20 luglio 2026 aggiornato da: 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.
Panoramica dello studio
Stato
Reclutamento
Intervento / Trattamento
Tipo di studio
Interventistico
Iscrizione (Stimato)
600
Fase
- Fase 3
Contatti e Sedi
Questa sezione fornisce i recapiti di coloro che conducono lo studio e informazioni su dove viene condotto lo studio.
Contatto studio
- Nome: ORIC Clinical Call Center
- Email: clinical@oricpharma.com
Luoghi di studio
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North Carolina
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Charlotte, North Carolina, Stati Uniti, 29464
- Reclutamento
- Urology Specialists of the Carolinas - University Place
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Investigatore principale:
- Jeremy Hubbard, MD
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Utah
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Murray, Utah, Stati Uniti, 84107
- Reclutamento
- Summit Urology
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Investigatore principale:
- Stewart Landau, MD
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Criteri di partecipazione
I ricercatori cercano persone che corrispondano a una certa descrizione, chiamata criteri di ammissibilità. Alcuni esempi di questi criteri sono le condizioni generali di salute di una persona o trattamenti precedenti.
Criteri di ammissibilità
Età idonea allo studio
- Adulto
- Adulto più anziano
Accetta volontari sani
No
Descrizione
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:
- Treatment with first-generation antiandrogen agents (eg, bicalutamide, flutamide, nilutamide), but must be discontinued prior to the first dose of study medication
- 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
Piano di studio
Questa sezione fornisce i dettagli del piano di studio, compreso il modo in cui lo studio è progettato e ciò che lo studio sta misurando.
Come è strutturato lo studio?
Dettagli di progettazione
- Scopo principale: Trattamento
- Assegnazione: Randomizzato
- Modello interventistico: Assegnazione parallela
- Mascheramento: Nessuno (etichetta aperta)
Armi e interventi
Gruppo di partecipanti / Arm |
Intervento / Trattamento |
|---|---|
|
Comparatore attivo: Investigational Arm
Rinzimetostat + darolutamide
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400 mg once daily (QD)
Altri nomi:
600 mg twice daily (BID)
Altri nomi:
|
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Comparatore attivo: Physician's Choice
Control Arm
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600 mg twice daily (BID)
Altri nomi:
160 mg once daily (QD)
Altri nomi:
75 mg/m2 intravenously (IV) every 21 days for up to 10 cycles
Altri nomi:
|
Cosa sta misurando lo studio?
Misure di risultato primarie
Misura del risultato |
Misura Descrizione |
Lasso di tempo |
|---|---|---|
|
Radiographic Progression Free Survival assessed by blinded independent central review (BICR) per RECIST v1.1 and Prostate Cancer Clinical Trials Working Group 3 (PCWG3)
Lasso di tempo: 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
|
Misure di risultato secondarie
Misura del risultato |
Misura Descrizione |
Lasso di tempo |
|---|---|---|
|
Overall Survival (OS)
Lasso di tempo: 5 years
|
OS is defined as time from date of randomization to date of death due to any cause
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5 years
|
|
Objective response rate (ORR)
Lasso di tempo: 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)
Lasso di tempo: 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
Lasso di tempo: 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
Lasso di tempo: 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
Lasso di tempo: 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
Lasso di tempo: 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)
Lasso di tempo: 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
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Randomization up to ~4 years
|
|
Change from baseline in health-related quality of life (HRQoL) per Functional Assessment of Cancer Therapy - Prostate (FACT-P)
Lasso di tempo: 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)
Lasso di tempo: 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)
Lasso di tempo: 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)
Lasso di tempo: 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)
Lasso di tempo: 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)
Lasso di tempo: 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)
Lasso di tempo: 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
Lasso di tempo: 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"
Lasso di tempo: 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
Lasso di tempo: 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
Lasso di tempo: 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)
Lasso di tempo: 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
Lasso di tempo: Randomization up to ~1 year
|
Rinzimetostat characterized by predose and postdose plasma concentrations at selected time points
|
Randomization up to ~1 year
|
Collaboratori e investigatori
Qui è dove troverai le persone e le organizzazioni coinvolte in questo studio.
Sponsor
Collaboratori
Studiare le date dei record
Queste date tengono traccia dell'avanzamento della registrazione dello studio e dell'invio dei risultati di sintesi a ClinicalTrials.gov. I record degli studi e i risultati riportati vengono esaminati dalla National Library of Medicine (NLM) per assicurarsi che soddisfino specifici standard di controllo della qualità prima di essere pubblicati sul sito Web pubblico.
Studia le date principali
Inizio studio (Stimato)
1 luglio 2026
Completamento primario (Stimato)
1 marzo 2028
Completamento dello studio (Stimato)
1 settembre 2030
Date di iscrizione allo studio
Primo inviato
18 giugno 2026
Primo inviato che soddisfa i criteri di controllo qualità
20 luglio 2026
Primo Inserito (Effettivo)
23 luglio 2026
Aggiornamenti dei record di studio
Ultimo aggiornamento pubblicato (Effettivo)
23 luglio 2026
Ultimo aggiornamento inviato che soddisfa i criteri QC
20 luglio 2026
Ultimo verificato
1 luglio 2026
Maggiori informazioni
Termini relativi a questo studio
Parole chiave
- sicurezza
- cancro alla prostata
- etichetta aperta
- efficacia
- enzalutamide
- abiraterone
- ricaduto
- refrattario
- carcinoma prostatico avanzato
- docetaxel
- resistente agli ormoni
- abiraterone acetato
- darolutamide
- carcinoma prostatico resistente alla castrazione metastatico (mCRPC)
- hormone dependent malignancy
- androgen receptor (AR) signaling
- androgen pathway modulator-resistant (APMR)
- metastatic castration sensitive prostate cancer (mCSPC)
- androgen pathway modulator-naïve/sensitive (APMN/S)
- polycomb repressive complex 2 (PRC2)-controlled dysregulation
- embryonic ectoderm development (EED)
- enhancer of zeste homolog 2 (EZH2)
- ORIC-944
- rinzimetostat
- mevrometostat
Termini MeSH pertinenti aggiuntivi
- Malattie urogenitali
- Malattie genitali
- Malattie del sistema nervoso centrale
- Malattie del sistema nervoso
- Processi patologici
- Neoplasie genitali, maschio
- Neoplasie urogenitali
- Neoplasie per sede
- Neoplasie
- Malattie genitali, maschio
- Malattie della prostata
- Malattie urogenitali maschili
- Malattie neuromuscolari
- Attributi della malattia
- Malattie genetiche, congenite
- Malattie Neurodegenerative
- Malattie Eredodegenerative, Sistema Nervoso
- Malattie genetiche, legate all'X
- Malattie del midollo spinale
- Malattia del motoneurone
- Atrofia muscolare, spinale
- Malattie e anomalie congenite, ereditarie e neonatali
- Condizioni patologiche, segni e sintomi
- Neoplasie prostatiche
- Ricorrenza
- Atrofia bulbo-spinale, legata all'X
- Prodotti chimici organici
- Idrocarburi
- Cicloparaffins
- Idrocarburi, aliciclici
- Idrocarburi, ciclici
- Terpeni
- Taxoidi
- Ciclodecani
- Diterpenes
- Docetaxel
- Daroutamide
- Enzalutamide
Altri numeri di identificazione dello studio
- ORIC-944-05
- 2026-525340-15-00 (Ctis)
Piano per i dati dei singoli partecipanti (IPD)
Hai intenzione di condividere i dati dei singoli partecipanti (IPD)?
NO
Informazioni su farmaci e dispositivi, documenti di studio
Studia un prodotto farmaceutico regolamentato dalla FDA degli Stati Uniti
Sì
Studia un dispositivo regolamentato dalla FDA degli Stati Uniti
No
prodotto fabbricato ed esportato dagli Stati Uniti
No
Queste informazioni sono state recuperate direttamente dal sito web clinicaltrials.gov senza alcuna modifica. In caso di richieste di modifica, rimozione o aggiornamento dei dettagli dello studio, contattare register@clinicaltrials.gov. Non appena verrà implementata una modifica su clinicaltrials.gov, questa verrà aggiornata automaticamente anche sul nostro sito web .