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

Browse trials for

• Prostatic Neoplasms 6,356
• Recurrence 4,278
• Bulbo-Spinal Atrophy, X-Linked 33

Keywords

• prostate cancer
• advanced prostate cancer
• hormone dependent malignancy
• hormone resistant
• relapsed
• refractory
• androgen receptor (AR) signaling
• metastatic castration resistant prostate cancer (mCRPC)
• 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
• darolutamide
• enzalutamide
• docetaxel
• abiraterone
• abiraterone acetate
• efficacy
• safety
• open-label

Study arms

• Active comparator
  Investigational Arm

  Rinzimetostat + darolutamide

  Drug: Rinzimetostat · Drug: Darolutamide

• Active comparator
  Physician's Choice

  Control Arm

  Drug: Darolutamide · Drug: Enzalutamide · Drug: Docetaxel

Interventions

• DrugRinzimetostat

  400 mg once daily (QD)

  Also known as: ORIC-944

• DrugDarolutamide

  600 mg twice daily (BID)

  Also known as: Nubeqa

• DrugEnzalutamide

  160 mg once daily (QD)

  Also known as: Xtandi

• DrugDocetaxel

  75 mg/m2 intravenously (IV) every 21 days for up to 10 cycles

  Also known as: Taxotere

Primary outcomes

1. Radiographic Progression Free Survival assessed by blinded independent central review (BICR) per RECIST v1.1 and Prostate Cancer Clinical Trials Working Group 3 (PCWG3)

   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

   Time frame: Randomization up to ~2 years

Secondary outcomes

1. Overall Survival (OS)

   OS is defined as time from date of randomization to date of death due to any cause

   Time frame: 5 years

2. Objective response rate (ORR)

   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)

   Time frame: Randomization up to ~2 years

3. Duration of Response (DoR)

   DOR is defined as time of first response to first documentation of radiographic progression or death, whichever occurs first

   Time frame: Randomization up to ~2 years

4. Prostate Specific Antigen (PSA) response

   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

   Time frame: Randomization up to ~2 years

5. Time to PSA progression

   Measured from the start of treatment until criteria for PSA progression are met as per PCWG3

   Time frame: Randomization up to ~2 years

6. Time to initiation of antineoplastic therapy

   Time from randomization to first symptomatic skeletal event (symptomatic bone fractures, spinal cord compression, surgery or radiation to the bone whichever is first)

   Time frame: Randomization up to ~4 years

7. Time to first symptomatic skeletal event

   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

   Time frame: Randomization up to ~4 years

8. Change from baseline in patient reported pain symptoms per Brief Pain Inventory-Short Form (BPI-SF)

   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

   Time frame: Randomization up to ~4 years

9. Change from baseline in health-related quality of life (HRQoL) per Functional Assessment of Cancer Therapy - Prostate (FACT-P)

   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

   Time frame: Randomization up to ~4 years

10. Change from baseline in social/family well-being per Functional Assessment of Cancer Therapy - Prostate (FACT-P)

    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

    Time frame: Randomization up to ~4 years

11. Change from baseline in functioning well-being per Functional Assessment of Cancer Therapy - Prostate (FACT-P)

    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

    Time frame: Randomization up to ~4 years

12. Change from baseline in physical well-being per Functional Assessment of Cancer Therapy - Prostate (FACT-P)

    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

    Time frame: Randomization up to ~4 years

13. Change from baseline in symptoms per Functional Assessment of Cancer Therapy - Prostate (FACT-P)

    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

    Time frame: Randomization up to ~4 years

14. Change from baseline in patient reported health status per European Quality of Life 5-Dimension 5 Level (EQ-5D-5L)

    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."

    Time frame: Randomization up to ~4 years

15. Symptomatic toxicity as measured by items from the Patient-Reported Outcome CTCAE (PRO-CTCAE)

    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

    Time frame: Randomization up to ~2 years

16. Overall side effect burden as measured by the FACT- GP5

    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

    Time frame: Randomization up to ~2 years

17. Time to confirmatory deterioration in patient-reported pain symptoms per BPI-SF Item 3 "worst pain in 24 hours"

    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

    Time frame: Randomization up to ~4 years

18. Time to definitive deterioration in patient-reported health related quality of life (HRQoL) per FACT-P

    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

    Time frame: Randomization up to ~4 years

19. Time to definitive deterioration in patient-reported physical well-being per FACT-P

    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

    Time frame: Randomization up to ~4 years

20. Incidence of Adverse Events (AEs)

    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

    Time frame: Randomization up to ~2 years

21. Evaluate the pharmacokinetics (PK) of rinzimetostat in combination with darolutamide

    Rinzimetostat characterized by predose and postdose plasma concentrations at selected time points

    Time frame: Randomization up to ~1 year

Individual participant data

Plan to share: No