A Phase 2, Open-label, Multi-centre Study of FPI-2265 (225Ac-PSMA-I&T) and Olaparib in Participants With Metastatic Castration Resistant Prostate Cancer (mCRPC)
试验速览
- 阶段
- 2 期
- 状态
- 进行中（未招募）
- 入组人数
- 85
- 试验地点
- 4
- 主要终点
- Evaluate anti-tumour activity of FPI-2265 administered in combination with olaparib
研究概览
简要总结
This study is an open-label, multicenter study designed to investigate the efficacy, safety and tolerability of FPI-2265 (225Ac-PSMA-I&T) in combination with Olaparib in participants with mCRPC. The dose optimization Phase 2 part will be investigating the safety, tolerability, and anti-tumor activity of novel dosing regimens of FPI-2265 and Olaparib in participants with metastatic castration-resistant prostate cancer.
详细描述
This study is an open-label, multicenter study designed to investigate the efficacy, safety and tolerability of FPI-2265 (225Ac-PSMA-I&T) in combination with Olaparib in participants with mCRPC. The study will be conducted in two parts, with Part A enrolling participants who have been previously treated with lutetium-177 (177Lu) vipivotide tetraxetan or other 177Lu-PSMA radioligand therapy (RLT) and Part B enrolling participants who have not been previously treated with lutetium-177 (177Lu) vipivotide tetraxetan or other 177Lu-PSMA radioligand therapy. For each part of the study, a Simon 2-stage design will be used to evaluate two dosing regimens. The purpose of this investigation is to determine the recommended FPI-2265 dose and regimen. Conclusions from this Phase 2 study will be based on safety, tolerability, and anti-tumor activity data. Participants with PSMA-positive mCRPC will be allocated to Arm 1 and Arm 2 in a singular, alternating fashion, until all Stage 1 participants are enrolled into each of the two regimens:
Arm 1: Will consist of up to six doses of FPI-2265 every six weeks at Dose A and olaparib twice a day on days 1 to 14 of each cycle.
Arm 2: Will consist of up to nine doses of FPI-2265 every four weeks at Dose B and olaparib twice a day on days 1 to 14 of each cycle Participants will be monitored and assessed for efficacy response, disease progression, and adverse events.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 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
- •Adult male participants with mCRPC that is progressing at the time of study entry
- •ECOG performance status 0-1 and life expectancy of at least three months
- •Must have received at least one novel anti-androgen deprivation therapy
- •Participants with known BRCA mutations should have received approved therapies such as PARP inhibitors, per Investigator discretion.
- •All prior treatment-related AEs must have resolved to CTCAE Grade ≤1 (except alopecia).
- •Participants must have had prior orchiectomy and/or ongoing androgen deprivation therapy and a castrate level of serum testosterone (<50 ng/dL or <1.7 nmol/L)
- •Positive PSMA PET/CT scans .
- •Participants must have adequate organ and bone marrow function:
- •Hgb >/= 9g/dL
- •Platelets >/= 100 x 10^9/L
- •ANC /= 50 mL/min
排除标准
- •Previous treatment with any of the following within 6 months of first dose: Samarium-153, Rhenium-186, Rhenium-188, Radium-223, hemi-body irradiation.
- •Participants who received more than two (2) prior lines of cytotoxic chemotherapy for CRPC.
- •Participants with known unresolved urinary tract obstruction.
- •Transfusion- or growth factor-dependent participants.
- •Participants with a history of CNS metastases are excluded, except those who have received therapy (and are neurologically stable, asymptomatic, and not receiving corticosteroids for the purposes of maintaining neurologic integrity.
- •Symptomatic cord compression, or clinical or radiologic findings indicative of impending cord compression.
- •Participants with any liver metastases.
- •Participants with skeletal metastases presenting as a superscan .
- •Previous history of interstitial lung disease or non-infectious pneumonitis.
- •Participants with a history or clinical and/or laboratory features suggestive of MDS/AML.
- •Major surgery ≤28 days prior to the first dose of study treatment.
- •Planning to conceive a pregnancy during the treatment and up to six months after the last treatment.
- •Participants unable to swallow orally administered medications or with malabsorptive gastrointestinal disorders.
- •Concomitant use of known strong or moderate CYP3A inhibitors or inducers
研究组 & 干预措施
Part A
Regimen 1: FPI-2265 (Dose A intravenously [IV] every six weeks) plus olaparib (twice daily [BID], on Days 1 to 14 of each cycle).
Regimen 2: . FPI-2265 (Dose B intravenously [IV] every 4 weeks) plus olaparib (twice daily [BID], on Days 1 to 14 of each cycle)
干预措施: FPI-2265 (Drug)
Part B
Regimen 1: FPI-2265 (Dose A intravenously [IV] every six weeks) plus olaparib (g twice daily [BID], on Days 1 to 14 of each cycle).
Regimen 2: . FPI-2265 (Dose B intravenously [IV] every 4 weeks) plus olaparib (twice daily [BID], on Days 1 to 14 of each cycle)
干预措施: FPI-2265 (Drug)
Part B
Regimen 1: FPI-2265 (Dose A intravenously [IV] every six weeks) plus olaparib (g twice daily [BID], on Days 1 to 14 of each cycle).
Regimen 2: . FPI-2265 (Dose B intravenously [IV] every 4 weeks) plus olaparib (twice daily [BID], on Days 1 to 14 of each cycle)
干预措施: Olaparib (Drug)
Part A
Regimen 1: FPI-2265 (Dose A intravenously [IV] every six weeks) plus olaparib (twice daily [BID], on Days 1 to 14 of each cycle).
Regimen 2: . FPI-2265 (Dose B intravenously [IV] every 4 weeks) plus olaparib (twice daily [BID], on Days 1 to 14 of each cycle)
干预措施: Olaparib (Drug)
结局指标
主要结局
Evaluate anti-tumour activity of FPI-2265 administered in combination with olaparib
时间窗: From first dose until approximately 12 weeks after the first administered dose of FPI-2265
The frequency and proportion of participants with PSA50 response will be summarized, where PSA50 is defined as ≥50% decline in PSA level from pre-treatment.
Evaluate the safety and tolerability of FPI-2265 administered in combination with olaparib
时间窗: From first dose until end of long-term follow-up, 5 years from the last administered dose of FPI-2265
Safety will be assessed by percentage of patient with treatment emergent adverse events and serious adverse events; percentage of patients with SAEs during the first year of the long term follow up and the number of AESIs during the 5 year follow up period. Percentage of patients with interruption of FPI-2265; percentage of patients who discontinue treatment; number and grade for AEs related to study treatment.
次要结局
未报告次要终点