Treatment of Metastatic Castration-Resistant Prostate Cancer With Homologous Recombination Deficiency

A Phase 2, Open-Label, Single-Arm Study of BGB-290 (BGB-290) for the Treatment of Patients With Metastatic Castration-Resistant Prostate Cancer (mCRPC) With Homologous Recombination Deficiency (HRD)

This study is designed to evaluate the efficacy of pamiparib in participants with metastatic castration-resistant prostate cancer (mCRPC) positive for circulating tumor cells (CTC) with homologous recombination deficiency (CTC-HRD). All participants will receive pamiparib. The purpose of this study is to demonstrate that pamiparib will improve Objective Response Rate (ORR) and Prostate-Specific Antigen (PSA) response rate

Study Overview

• Status: Terminated
• Conditions: Metastatic Castration-Resistant Prostate Cancer (mCRPC); Homologous Recombination Deficiency (HRD)
• Intervention / Treatment: Drug: Pamiparib

Detailed Description

This is a global, Phase 2, open-label study of pamiparib in approximately 100 participants with metastatic castration-resistant prostate cancer (mCRPC) positive for circulating tumor cells (CTC) with homologous recombination deficiency (CTC-HRD). Participants in Cohort 1 will include 50 mCRPC participants with CTC-HRD-positive, measurable metastatic disease (soft tissue with/without bone lesions), and positive BRCA1/2 mutation or negative/unknown BRCA1/2 mutation. Cohort 2 will include 30 mCRPC CTC-HRD positive participants with bone metastasis only and positive or negative/unknown BRCA1/2. Cohort 3 and 4 will include 20 mCRPC CTC-HRD negative/unknown participants with BRCA1/2 positive mutations, metastatic disease (measurable soft tissue with/without bone), and bone only. Participants will undergo PSA level assessments approximately every 4 weeks as well as tumor assessments every 8 weeks for 24 weeks and the every 12 weeks, or as clinically indicated. Administration of pamiparib will continue until disease progression, unacceptable toxicity, death or another discontinuation criterion is met.

• Study Type: Interventional
• Enrollment (Actual): 13
• Phase: Phase 2

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Gosford, New South Wales, Australia, 2250
      • Gosford Hospital
    • Liverpool, New South Wales, Australia, 2170
      • Liverpool Hospital
    • Waratah, New South Wales, Australia, 2298
      • Calvary Mater Newcastle
  • Queensland
    • South Brisbane, Queensland, Australia, 044101
      • Icon Cancer Care Foundation
• Puerto Rico
  • Rio Piedras, Puerto Rico, 935
    • Pan American Oncology Trials, LLC
• Spain
  • Barcelona, Spain, 8035
    • L Hospitalet de Llobregat
• United States
  • Georgia
    • Athens, Georgia, United States, 30607
      • University Cancer and Blood Center
  • New York
    • Bronx, New York, United States, 10461
      • Montefiore Einstein Cancer Center
  • Washington
    • Seattle, Washington, United States, 98195
      • University of Washington

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

Key Inclusion Criteria:

• Men (≥ 18 years of age) with histologically or cytologically confirmed adenocarcinoma or poorly differentiated adenocarcinoma of the prostate without neuroendocrine differentiation with HRD deficiency by CTC-HRD assay and/or deleterious germline or somatic mutation in BRCA1 or BRCA2; mCRPC measurable disease and/or bone disease. • PSA progression with ≥ 3 rising PSA levels with ≥ 1 week between determinations and a screening PSA ≥ 2 μg/L (2 ng/mL).
• Must be surgically or medically castrated with serum testosterone levels of ≤1.73 nmol/L (50 ng/dL), must have received ≥ 1 prior androgen receptor-targeted therapy, and must have received ≥ 1 taxane-based therapy.
• mCRPC with 1 or 2 of the following:
• Measurable disease per RECIST v1.1
• Bone disease
• CTC-HRD+ or BRCA1/2 mutation
• PSA progression (PCWG3 criteria)
• ≥1 androgen receptor-targeted therapy (eg, abiraterone acetate/prednisone or enzalutamide) for mCRPC with progressive disease
• ≥1 taxane for metastatic prostate cancer

Key Exclusion Criteria:

• Chemotherapy, hormonal therapy, biologic therapy, radionuclide therapy, immunotherapy, investigational agent, anticancer Chinese medicine, or herbal remedies ≤ 5 half-lives if the half-life is known, ≤ 14 days if not known, before start of study treatment
• Continued treatment with a bisphosphonate or denosumab is allowed, if administered at a stable dose > 28 days before start of study treatment
• Radiotherapy ≤ 21 days (≤ 14 days, if single fraction of radiotherapy) before start of study treatment

Prior treatment for prostate cancer with any of the following:

• poly ADP ribose polymerase (PARP) inhibitor
• Platinum
• Cyclophosphamide
• Mitoxantrone

NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Pamiparib; Participants will receive pamiparib for a period up to 1 year	Drug: Pamiparib; 60 mg orally twice daily (BID); Other Names: BGB-290

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective Response Rate (ORR) Determined by Independent Review Committee	ORR is the percentage of participants with a best objective response of complete response (CR) or partial response (PR) confirmed at a subsequent timepoint ≥ 4 weeks later by an Independent Review Committee (IRC).	Up to 1 year and 6 months
Prostate-Specific Antigen (PSA) Response Rate	PSA response rate is defined as the percentage of participants with PSA decline ≥ 50% from baseline [confirmed by a second PSA value ≥ 3 weeks later] for CTC-HRD-positive participants with or without measurable disease.	Up to 1 year and 6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Duration of Response (DOR) by IRC	DOR is defined as the time from the date of the earliest documented CR or PR (that is subsequently confirmed) to radiographic disease progression or death due to any cause, whichever occurs first.	Up to 1 year and 7 months
Objective Response Rate by Investigator	ORR is the percentage of participants with a best objective response of complete response (CR) or partial response (PR) confirmed at a subsequent timepoint ≥ 4 weeks later by the investigator.	Up to 1 year and 6 months
Time to Objective Response by Investigator	Time to objective response is defined as the time from the date of the first dose of study drug to the first documented confirmed response of CR or PR assessed by the investigator and summarized for participants who have achieved a confirmed objective response.	Up to 1 year and 6 months
Clinical Benefit Rate By Investigator	Clinical Benefit Rate is the percentage of participants who achieved confirmed CR, PR, or SD or NON-CR/NON-PD. The minimum interval for confirmed CR and PR is 4 weeks and the measurement of SD or NON-CR/NON-PD is 7 weeks after first dose date.	Up to 1 year and 6 months
Time to PSA Response	Time to PSA response is defined as the time from the date of the first dose of study drug to the first PSA decline ≥ 50% that is subsequently confirmed. Assessments are summarized for participants who have achieved a confirmed PSA response.	Up to 1 year and 6 months
Duration of PSA Response	Duration of PSA response is defined as the time from the date of the earliest documented PSA response (that is subsequently confirmed) to PSA progression or death due to any cause, whichever occurs first. PSA progression is defined as a ≥ 25% increase in PSA with an absolute increase of ≥ 2 μg/L above the nadir (or above the baseline for participants with no PSA decline) after12 weeks, confirmed by a second value ≥ 3 weeks later. The nadir is defined as the lowest value at or after baseline.	Up to 1 year and 7 months
Time to PSA Progression	Time to PSA progression is defined as the time from the date of the first dose of study drug to a ≥ 25% increase in PSA with an absolute increase of ≥ 2 ng/mL above the nadir (or above the baseline for participants with no PSA decline) after 12 weeks, confirmed by a second value ≥ 3 weeks later. Death for the participants with no PSA progression is also considered as an event.	Up to 1 year and 7 months
Time to Symptomatic Skeletal Event	Time to symptomatic skeletal event (SSE) is defined as time from the date of the first dose of study drug to the first symptomatic fracture, radiation or surgery to bone, or spinal cord compression.	Up to 1 year and 7 months
Radiographic Progression-Free Survival by IRC	Radiographic progression-free survival is defined as the time from the date of the first dose of study drug to radiographic disease progression by IRC or death due to any cause, whichever occurs first.	Up to 1 year and 7 months
Overall Survival (OS)	Overall survival is defined as the time from the date of the first dose of study drug to death due to any cause.	Up to 1 year and 7 months
Number of Participants With Treatment-Emergent Adverse Events Graded According to National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) Version 4.03		From the date of first Pamiparib dose until 30 days after the last dose or initiation of new anti-cancer therapy, whichever occurs first. (Up to 1 year and 7 months)

Collaborators and Investigators

• Sponsor: BeiGene
• Investigators: Principal Investigator: Study Director, Guy's and St Thomas' NHS Foundation Trust

Study record dates

Study Major Dates

• Study Start (Actual): February 5, 2019
• Primary Completion (Actual): August 6, 2020
• Study Completion (Actual): September 2, 2020

Study Registration Dates

• First Submitted: October 11, 2018
• First Submitted That Met QC Criteria: October 17, 2018
• First Posted (Actual): October 19, 2018

Study Record Updates

• Last Update Posted (Actual): November 17, 2021
• Last Update Submitted That Met QC Criteria: October 20, 2021
• Last Verified: October 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Genital Neoplasms, Male; Prostatic Diseases; Prostatic Neoplasms
• Other Study ID Numbers: BGB-290-202; 2018-002587-28 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No