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)
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 发起方
- 入组人数
- 13
- 试验地点
- 9
- 主要终点
- Objective Response Rate (ORR) Determined by Independent Review Committee
研究概览
简要总结
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
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- Male
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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
- •Cyclophosphamide
- •Mitoxantrone
- •NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.
研究组 & 干预措施
Pamiparib
Participants will receive pamiparib for a period up to 1 year
干预措施: Pamiparib (Drug)
结局指标
主要结局
Objective Response Rate (ORR) Determined by Independent Review Committee
时间窗: Up to 1 year and 6 months
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).
Prostate-Specific Antigen (PSA) Response Rate
时间窗: Up to 1 year and 6 months
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.
次要结局
- Time to PSA Response(Up to 1 year and 6 months)
- Time to Objective Response by Investigator(Up to 1 year and 6 months)
- Clinical Benefit Rate By Investigator(Up to 1 year and 6 months)
- Overall Survival (OS)(Up to 1 year and 7 months)
- Duration of Response (DOR) by IRC(Up to 1 year and 7 months)
- Objective Response Rate by Investigator(Up to 1 year and 6 months)
- Time to PSA Progression(Up to 1 year and 7 months)
- Duration of PSA Response(Up to 1 year and 7 months)
- Time to Symptomatic Skeletal Event(Up to 1 year and 7 months)
- Radiographic Progression-Free Survival by IRC(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))