Niraparib Combinations for Prostate Cancer

(QUEST Trial)

Recruiting at52 trial locations

Age: 18+

Sex: Male

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1 & 2

Waitlist Available

Sponsor: Janssen Research & Development, LLC

No Placebo Group

Breakthrough Therapy

Trial Summary

What is the purpose of this trial?

The purpose of this study is to: a) establish the recommended phase 2 dose (RP2D) and to evaluate the antitumor activity and safety of niraparib combination therapies (Combinations 1 and 2) and b) to determine the relative bioavailability of niraparib and abiraterone acetate (AA) in combination (Combination 3) in participants with metastatic castration-resistant prostate cancer (mCRPC).

Research Team

Janssen Research & Development, LLC Clinical Trial

Principal Investigator

Janssen Research & Development, LLC

Eligibility Criteria

Men with metastatic castration-resistant prostate cancer who've had disease progression during treatment with abiraterone acetate and PARPi, or stopped these treatments due to side effects. They must have a good performance status (able to carry out daily activities) and resolved any previous treatment toxicities to an acceptable level. Participants should not donate sperm during the trial.

Inclusion Criteria

I can continue hormone therapy during the study if I haven't had surgery to remove my testicles.

Participant must agree not to donate sperm while on study treatment, and for 3 months following the last dose of study treatment

Side effects from my previous cancer treatments are mild or gone, except for hair loss or some nerve issues.

Exclusion Criteria

I have no active cancers except for certain skin, bladder, or breast cancers, or any cancer considered cured.

I am currently being treated for an infection.

My condition worsened on AA and PARPi treatment, or I stopped due to side effects.

Treatment Details

Interventions

• Abiraterone acetate (Androgen Receptor Inhibitor)
• Cetrelimab (PD-1 Inhibitor)
• Niraparib (PARP Inhibitor)
• Prednisone 5 mg (Corticosteroid)

Trial Overview The study is testing combinations of Niraparib with other drugs like Prednisone, Cetrelimab, and Abiraterone acetate in different doses for treating advanced prostate cancer. It aims to find the best dose for phase 2 trials, assess how well tumors respond, check safety, and understand how Niraparib and Abiraterone are absorbed together.

Participant Groups

Group I: Combination 3: Niraparib + AA-P Experimental Treatment 3 Interventions

Participants will be assigned to one of three cohorts to receive AA-P with or without niraparib. Participants in the Treatment Phase of this combination will be offered the option to enter the Long-term Extension Phase of the study.

Group II: Combination 2: Dose Expansion: Niraparib + AA-P (Part 2) Experimental Treatment 3 Interventions

Participants will be assigned to one of 4 cohorts based on biomarker status - Cohort 2A (BRCA biallelic loss), 2B (other DRD biallelic loss), 2C (BRCA monoallelic loss), or 2D (other DRD monoallelic loss), and will receive niraparib 200 mg once daily in combination with abiraterone acetate 1000 mg (4\*250 mg) plus 10 mg prednisone (5 mg twice daily) throughout treatment phase. Participants in the Treatment Phase of this combination will be offered the option to enter the Long-term Extension Phase of the study.

Group III: Combination 1:Dose Selection: Niraparib + cetrelimab (Part 1) Experimental Treatment 3 Interventions

Dose regimen 1: The participants will receive niraparib 200 milligram (mg) orally once daily in combination with cetrelimab 240 mg intravenously (IV) once every 2 weeks. Dose regimen 2: The participants will receive niraparib 200 mg orally once daily in combination with cetrelimab 480 mg IV once every 4 weeks in 28-day treatment cycles until disease progression, unacceptable toxicity, death, or the sponsor terminates the study. The safety evaluation team (SET) will determine if an additional cohort is necessary, based on the data from dose regimens 1 and 2. Participants in the Treatment Phase of this combination will be offered the option to enter the Long-term Extension Phase of the study.

Group IV: Combination 1:Dose Expansion: Niraparib + cetrelimab (Part 2) Experimental Treatment 2 Interventions

Participants will be assigned to either Cohort 1A (Biomarker \[BM\] positive \[+\]) or Cohort 1B (BM negative \[-\]) and will receive established RP2D of cetrelimab and niraparib, in Part 2 until disease progression, unacceptable toxicity, death, or the sponsor terminates the study. A futility analysis will be performed for the Cohort 1B after 10 BM- participants are enrolled in Part 2. This cohort will be closed if the response is less than predetermined response rate as outlined in the protocol. Participants in the Treatment Phase of this combination will be offered the option to enter the Long-term Extension Phase of the study.

Abiraterone acetate is already approved in Canada, Japan for the following indications:

Approved in Canada as Zytiga for:

• Metastatic castration-resistant prostate cancer

Approved in Japan as Zytiga for:

• Metastatic castration-resistant prostate cancer

Who Is Running the Clinical Trial?

Janssen Research & Development, LLC

Lead Sponsor

Trials

1,022

Recruited

6,408,000+

Giacomo Salvadore

Janssen Research & Development, LLC

Chief Medical Officer since 2023

MD from the University of Rome, Tor Vergata

Ricardo Attar

Janssen Research & Development, LLC

Chief Executive Officer since 2008

PhD in Molecular Biology from the University of Buenos Aires