A Phase II, Randomized, Open-label, Multi-center Study of JSB462 (Luxdegalutamide) in Combination With Lutetium (177Lu) Vipivotide Tetraxetan in Adult Male Patients With PSMA-positive 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
- 138
- 试验地点
- 52
- 主要终点
- Incidence rate of adverse events (AEs)
研究概览
简要总结
This Phase II study aims to evaluate the efficacy and safety of the combination of JSB462 (also known as luxdegalutamide) at 100 mg and 300 mg QD doses + lutetium (177Lu) vipivotide tetraxetan (hereafter referred as AAA617) compared with AAA617 (control) in participants with metastatic Castration Resistant Prostate Cancer (mCRPC) with prior exposure to at least 1 Androgen Receptor Pathway Inhibitor (ARPI) and 0-2 taxane regimens and to select the recommended dose of the combination for phase III. Towards that end, the totality of the efficacy, safety, tolerability and pharmacokinetic (PK) data from participants randomized in the study will be evaluated.
详细描述
The study consists of a screening period, a randomization period, a treatment period, a post-treatment safety follow-up followed by a long-term follow-up period.
JSB462 administration starts at day 1 of randomization, whereas AAA617 administration starts at day 1 of treatment period. Participants in arm 1 and arm 2 will therefore receive JSB462 during the 14-day randomization period before first administration of AAA617.
- JSB462 is administered orally, daily and continuously (100 mg or 300 mg once a day (QD)) until disease progression per Prostate Cancer Working Group (PCWG) 3-modified Response Evaluation Criteria In Solid Tumors (RECIST) v1.1 as assessed by the investigator, the occurrence of unacceptable toxicities, death, participant decision or investigator decision.
- AAA617 will be administered at 7.4 gigabecquerel (GBq) intravenously every 6 weeks for up to 6 doses, unless there is disease progression per PCWG3-modified RECIST v1.1 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 end of treatment visit). 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 the 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
- •Adult male participants with histologically and/or cytologically confirmed adenocarcinoma of the prostate. Participants with mixed histology (neuroendocrine) are not eligible.
- •An Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) grade ≤
- •At least 1 bone or visceral metastatic lesion present on baseline CT, MRI, or bone scan imaging obtained ≤28 days prior to initiation of study treatment.
- •Participants must be [68Ga]Ga-PSMA-11 PET/CT scan positive and eligible as determined by the sponsor's central reader.
- •Participant must have prior exposure to at least one second generation ARPI in the metastatic/advanced setting.
- •Previous treatment with a maximum of 2 taxane regimens is allowed.
- •Participants eligible for PARPi and/or immune checkpoint inhibitor (per local testing and according to investigator's judgement) are eligible to participate if they have previous exposure to this(these) therapy(ies).
排除标准
- •Prior treatment with any RLT (approved or investigational) is not allowed
- •Prior treatment with a protein degrader compound that targets AR is not allowed
- •Other protocol-defined inclusion/exclusion criteria may apply.
研究组 & 干预措施
Arm 2
JSB462 300 mg QD + AAA617 7.4 GBq Q6W
干预措施: JSB462 (Drug)
Arm 1
JSB462 100 mg QD + AAA617 7.4 GBq Q6W
干预措施: JSB462 (Drug)
Arm 2
JSB462 300 mg QD + AAA617 7.4 GBq Q6W
干预措施: AAA617 (Drug)
Arm 1
JSB462 100 mg QD + AAA617 7.4 GBq Q6W
干预措施: AAA617 (Drug)
Arm 3
AAA617 7.4 GBq Q6W
干预措施: AAA617 (Drug)
结局指标
主要结局
Incidence rate of adverse events (AEs)
时间窗: From date of randomization till 30 days safety fup, assessed up to approximately 30 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 30 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 30 months
Dose interruptions, dose reductions, drug discontinuations, dose intensity, and duration of exposure to study treatment (all study drugs).
Prostate Specific Antigen 50 (PSA50) Rate
时间窗: From date of randomization till 30 days safety fup, assessed up to approximately 30 months
Prostate Specific Antigen 50 (PSA50) Rate is defined as the proportion of participants who achieve a ≥50% decrease from baseline at any timepoint, confirmed by a second PSA measurement ≥3 weeks without any PSA progression in between
次要结局
- 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 41 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 41 months)
- Volume of distribution during the terminal phase following intravenous elimination (Vz) of AAA617(Cycle 1: Day 1 (pre-dose/0hour, end of infusion (EOI), 1hour ±15minutes, 4hours ±30minutes), Day 2 (24hours ±2hours), Day 3 (48hours ±2hours), Day 8 (168hours ±12hours).Cycles 3 & 5: Day 1 (pre-dose/0hour, EOI), Day 3 (48hours ±2hours). 1 cycle=6 weeks.)
- Overall Survival (OS)(From date of randomization until date of death from any cause, assessed up to approximately 41 months)
- Prostate Specific Antigen 90 (PSA90) Rate(From date of randomization till 30 days safety fup, assessed up to approximately 30 months)
- Prostate Specific Antigen 0 (PSA0) Rate(From date of randomization till 30 days safety fup, assessed up to approximately 30 months)
- Observed maximum blood concentration (Cmax) of AAA617(Cycle 1: Day 1 (pre-dose/0hour, end of infusion (EOI), 1hour ±15minutes, 4hours ±30minutes), Day 2 (24hours ±2hours), Day 3 (48hours ±2hours), Day 8 (168hours ±12hours).Cycles 3 & 5: Day 1 (pre-dose/0hour, EOI), Day 3 (48hours ±2hours). 1 cycle=6 weeks.)
- Time of maximum observed blood concentration occurrence (Tmax) of AAA617(Cycle 1: Day 1 (pre-dose/0hour, end of infusion (EOI), 1hour ±15minutes, 4hours ±30minutes), Day 2 (24hours ±2hours), Day 3 (48hours ±2hours), Day 8 (168hours ±12hours).Cycles 3 & 5: Day 1 (pre-dose/0hour, EOI), Day 3 (48hours ±2hours). 1 cycle=6 weeks.)
- Terminal elimination half-life (T1/2) of AAA617(Cycle 1: Day 1 (pre-dose/0hour, end of infusion (EOI), 1hour ±15minutes, 4hours ±30minutes), Day 2 (24hours ±2hours), Day 3 (48hours ±2hours), Day 8 (168hours ±12hours).Cycles 3 & 5: Day 1 (pre-dose/0hour, EOI), Day 3 (48hours ±2hours). 1 cycle=6 weeks.)
- 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 41 months)
- Incidence rate of adverse events (AEs)(From date of randomization until date of death from any cause, assessed up to approximately 41 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 41 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 41 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 41 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 41 months)
- Time to first symptomatic skeletal event (TTSSE)(From randomization until the first occurrence of a new symptomatic bone fracture, spinal cord compression, tumor-related orthopedic surgery, radiation therapy for bone pain, or death, assessed up to 41 months.)
- Plasma concentrations of JSB462 and plasma concentrations of its metabolite ARV-767(Day 1 of Cycles 1 and 2: Pre-dose/0hour and Post-dose 4hour +/- 1hour. Day 1 of Cycles 3 to 6: Pre-dose/0hour. End of Treatment Visit (EOT): through study treatment discontinuation, an average of 24 months. 1 cycle = 28 days.)
- Concentrations of AAA617 in blood over time and PK parameters from blood radioactivity data(Cycle 1: Day 1 (pre-dose/0hour, end of infusion (EOI), 1hour ±15minutes, 4hours ±30minutes), Day 2 (24hours ±2hours), Day 3 (48hours ±2hours), Day 8 (168hours ±12hours).Cycles 3 & 5: Day 1 (pre-dose/0hour, EOI), Day 3 (48hours ±2hours). 1 cycle=6 weeks.)
- Prostate Specific Antigen 30 (PSA30) Rate(From date of randomization till 30 days safety fup, assessed up to approximately 30 months)
- Area under the AAA617 concentration-time curve from time zero to the time of last quantifiable concentration (AUClast)(Cycle 1: Day 1 (pre-dose/0hour, end of infusion (EOI), 1hour ±15minutes, 4hours ±30minutes), Day 2 (24hours ±2hours), Day 3 (48hours ±2hours), Day 8 (168hours ±12hours).Cycles 3 & 5: Day 1 (pre-dose/0hour, EOI), Day 3 (48hours ±2hours). 1 cycle=6 weeks.)
- Area under the concentration-time curve from time zero (pre-dose) extrapolated to infinite time (AUCinf) of AAA617(Cycle 1: Day 1 (pre-dose/0hour, end of infusion (EOI), 1hour ±15minutes, 4hours ±30minutes), Day 2 (24hours ±2hours), Day 3 (48hours ±2hours), Day 8 (168hours ±12hours).Cycles 3 & 5: Day 1 (pre-dose/0hour, EOI), Day 3 (48hours ±2hours). 1 cycle=6 weeks.)
- Patient Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE)(From date of randomization until date of death from any cause, assessed up to approximately 41 months)
- Total systemic clearance for intravenous administration (CL) of AAA617(Cycle 1: Day 1 (pre-dose/0hour, end of infusion (EOI), 1hour ±15minutes, 4hours ±30minutes), Day 2 (24hours ±2hours), Day 3 (48hours ±2hours), Day 8 (168hours ±12hours).Cycles 3 & 5: Day 1 (pre-dose/0hour, EOI), Day 3 (48hours ±2hours). 1 cycle=6 weeks.)
- Radiation absorbed doses in organs and tumors for AAA617(Cycle 1: Day 1 (1-4 hours), Day 2 (24 hours ±6 hours), Day 3 (48 hours ±6 hours), Day 8 (168 hours ±24 hours). Cycle 3: Day 1 (1-4 hours), Day 3 (48 hours ±6 hours). Cycle 5b (fit patients): Day 1 (1-4 hours), Day 3 (48 hours ±6 hours). 1 cycle=6 weeks.)