A Phase II, Randomized, Open-label, Multi-center Study of JSB462 (Luxdegalutamide) in Combination With Abiraterone in Adult Male Patients With Metastatic Hormone-sensitive Prostate Cancer (mHSPC)
试验速览
- 阶段
- 2 期
- 状态
- 进行中（未招募）
- 入组人数
- 168
- 试验地点
- 173
- 主要终点
- Prostate Specific Antigen 90 (PSA90) Rate
研究概览
简要总结
This Phase II study aims to evaluate efficacy and safety of the combination of JSB462 (also known as luxdegalutamide) at 100 mg and 300 mg once a day (QD) doses + abiraterone compared with an androgen receptor pathway inhibitor (ARPI, abiraterone or enzalutamide) in participants with metastatic Hormone Sensitive Prostate Cancer (mHSPC) and to select the recommended dose of the combination for phase III. Towards that end, the totality of the efficacy, safety, tolerability and PK data from participants randomized in the study will be evaluated
详细描述
The study for each participant consists of a Screening period (28 days), a treatment period, a post-treatment safety follow-up (30 days) followed by a long-term follow-up period.
During the treatment period:
- JSB462 is administered from randomization, orally, daily and continuously (100 mg or 300 mg QD) until disease progression per PCWG3-modified RECIST 1.1 as assessed by the investigator, the occurrence of unacceptable toxicities, death, participant decision or investigator decision.
- Abiraterone 1000 mg or enzalutamide 160 mg are administered from randomization, orally, daily, and continuously until disease progression per PCWG3-modified RECIST 1.1 as assessed by the investigator, the occurrence of unacceptable toxicities, death, participant decision or investigator decision.
During the post-treatment follow up period:
- Safety follow-Up: After discontinuation of study treatment, all participants will be followed for at least 1 safety follow-up visit (30 days [+/- 7 days] after treatment discontinuation). Subsequent lines of therapy may be administered according to investigator's discretion after treatment discontinuation.
- Long-term follow-up: Starts after the Safety follow-up period and lasts until the end of study. Safety, efficacy and survival information may be collected from participants during this period.
研究设计
- 研究类型
- Interventional
- 分配方式
- 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
- •An Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) ≤2
- •Histologically confirmed adenocarcinoma of the prostate. Participants with mixed histology (neuroendocrine) are not eligible
- •High-volume mHSPC, defined by the presence of ≥1 metastatic visceral non-nodal lesion and/or ≥4 metastatic bone lesions (with at least one lesion outside the vertebral column and/or pelvis) in imaging exams (CT/MRI or bone scan) according to local radiology assessment by the investigator obtained ≤28 days prior to randomization
- •Participants must have a castrate level of serum/plasma testosterone (<50 ng/dL or <1.7 nmol/L). Ongoing ADT (as defined by prior orchiectomy and/or ongoing GnRH analog/antagonist) for ≤90 days is allowed prior to randomization, provided that PSA zero (PSA level <0.2 ng/ml according to local laboratory as assessed by the investigator) is not achieved prior to randomization.
排除标准
- •Prior exposure to a second generation ARPI (such as enzalutamide/darolutamide/apalutamide and/or abiraterone) for the treatment of advanced/metastatic disease is not allowed. Prior exposure to ARPI, to taxane chemotherapy (up to 6 cycles) or to RLT in the context of (neo)adjuvant treatment for localized prostate cancer is allowed, if the last dose of this treatment was administered >12 months from randomization. Prior use of a first generation ARPI (such as bicalutamide) in the context of ADT initiation with a GnRH analog is allowed, provided the first generation ARPI was administered for ≤14 days and last dose was administered ≥7 days from randomization.
- •Participants with biochemical recurrence only or those without evidence of metastatic disease by radiological imaging (CT/MRI or bone scan) are not eligible
- •Other inclusion/exclusion criteria may apply.
研究组 & 干预措施
Arm 3
abiraterone 1000 mg QD or enzalutamide 160 mg QD
干预措施: Enzalutamide (Drug)
Arm 1
JSB462 100 mg QD + abiraterone 1000 mg QD
干预措施: Abiraterone (Drug)
Arm 3
abiraterone 1000 mg QD or enzalutamide 160 mg QD
干预措施: Abiraterone (Drug)
Arm 2
JSB462 300 mg QD + abiraterone 1000 mg QD
干预措施: Abiraterone (Drug)
Arm 2
JSB462 300 mg QD + abiraterone 1000 mg QD
干预措施: JSB462 (Drug)
Arm 1
JSB462 100 mg QD + abiraterone 1000 mg QD
干预措施: JSB462 (Drug)
结局指标
主要结局
Prostate Specific Antigen 90 (PSA90) Rate
时间窗: From date of randomization till 30 days safety fup, assessed up to approximately 75 months
Prostate Specific Antigen 90 (PSA90) Rate is defined as the proportion of participants who achieve a ≥90% decrease in PSA from baseline at any timepoint, confirmed by a second PSA measurement ≥3 weeks without any PSA progression in between.
Incidence rate of adverse events (AEs)
时间窗: From date of randomization till 30 days safety fup, assessed up to approximately 75 months
The analysis of adverse events will include categorization by type, frequency, and severity, as graded by the NCI CTCAE version 5.0.
Number of participants with dose adjustments
时间窗: From date of randomization till 30 days safety fup, assessed up to approximately 75 months
The number of participants with dose adjustments (reductions, interruption, or permanent discontinuation) will be summarized by treatment arm.
Duration of exposure to study treatment
时间窗: From date of randomization till 30 days safety fup, assessed up to approximately 75 months
The duration of exposure in weeks to study treatment and for each study treatment component (JSB462, abiraterone and enzalutamide) will be summarized for each study treatment component by means of descriptive statistics using the SAS.
次要结局
- Radiographic Progression Free Survival (rPFS)(From date of randomization until date of radiographic progression or date of death from any cause, whichever comes first, assessed up to approximately 83 months)
- Overall Survival (OS)(From date of randomization until date of death from any cause, assessed up to approximately 83 months)
- Incidence rate of adverse events (AEs)(From date of randomization till 30 days safety fup, assessed up to approximately 83 months)
- Overall Response Rate (ORR)(From date of randomization until date of progression or date of death from any cause, whichever come first, assessed up to approximately 83 months)
- Disease Control Rate (DCR)(From date of randomization until date of progression or date of death from any cause, whichever come first, assessed up to approximately 83 months)
- Duration of Response (DOR)(From date of randomization until date of progression or date of death from any cause, whichever come first, assessed up to approximately 83 months)
- Time to Response (TTR)(From date of randomization until date of first documented Complete Response (CR) or Partial Response (PR), assessed up to approximately 83 months)
- Time to soft tissue progression (TTSTP)(From date of randomization until date of soft tissue radiographic progression or date of death from any cause, whichever comes first, assessed up to approximately 83 months)
- Prostate Specific Antigen 30 (PSA30) Rate(From date of randomization till 30 days safety fup, assessed up to approximately 75 months)
- Prostate Specific Antigen 50 (PSA50) Rate(From date of randomization till 30 days safety fup, assessed up to approximately 75 months)
- Prostate Specific Antigen 0 (PSA0) Rate(From date of randomization till 30 days safety fup, assessed up to approximately 75 months)
- Duration of biochemical response (DBR)(From date of date of first PSA50 response until date of PSA progression or death from any cause, assessed up to approximately 83 months)
- Time to first symptomatic skeletal event (TTSSE)(From date of randomization till EOT or death, whichever happens first, assessed up to approximately 83 months)
- Plasma concentrations of JSB462 and plasma concentrations of its metabolite ARV-767(Day 1 of Cycles 1 and 2: Pre-dose/0h and Post-dose 4h +/- 1h. Day 1 of Cycles 3 to 8: Pre-dose/0h. End of Treatment Visit (EOT): Anytime. 1 cycle = 28 days.)
- Patient Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE)(From randomization up till 30 day safety Follow-up, assessed up to approximately 83 months)