PSMAcTION: A Phase II/III, Open-label, International, Multicenter, Randomized Study of AAA817 Versus Standard of Care in the Treatment of Adult Participants With PSMA Positive Metastatic Castration-resistant Prostate Cancer Who Progressed on or After [177Lu]Lu-PSMA Targeted Therapy
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 443
- 试验地点
- 93
- 主要终点
- Radiographic progression-free survival (rPFS)- Phase III
研究概览
简要总结
This is a Phase II/III study. Patient population is adult participants with PSMA-positive mCRPC who had treatments with androgen receptor pathway inhibitor (ARPI) and taxane-based chemotherapy and progressed on or after [177Lu]Lu-PSMA targeted therapy.
Treatment of interest: the investigational treatment is AAA817 regardless of subsequent anti-neoplastic treatment. The control treatment is investigator's choice of Standard of Care, regardless of subsequent anti-neoplastic treatment
详细描述
Study CAAA817A12201 consists of 2 parts: a randomized, open-label, international, multicenter, phase II study (Phase II) to collect more information to support the proposed dose of AAA817 and a randomized, open-label, international, multicenter, 2- arm phase III study (Phase III) aimed to evaluate the efficacy and safety of proposed dose of AAA817 vs. investigator's choice of standard of care (SoC) in the treatment of adult participants with PSMA-positive metastatic castration-resistant prostate cancer (mCRPC) who had treatments with ARPI and taxane-based chemotherapy, and progressed on or after [177Lu]Lu-PSMA targeted therapy. The purpose of the phase II part (Phase II) of this study is to collect additional information to support proposed phase III dose of AAA817.
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 100 Years（Adult, Older Adult）
- 性别
- Male
- 接受健康志愿者
- 否
入选标准
- •adults ≥ 18 years of age.
- •ECOG performance status of 0 to
- •histopathological and/or cytological confirmation of adenocarcinoma of the prostate.
- •PSMA-positive disease as assessed by PSMA PET/CT scan using an approved PSMA imaging agent as protocol instructed,
- •castrate level of serum/plasma testosterone (< 50 ng/dL or < 1.7 nmol/L).
- •Prior treatments with an androgen receptor pathway inhibitor (ARPI) and taxane-based chemotherapy, and progressed on or after [177Lu]Lu-PSMA targeted therapy.
- •≥ 1 metastatic lesion that is present on screening/baseline CT, MRI, or bone scan imaging obtained ≤ 28 days prior to randomization
- •eGFR as requested by the sponsor
排除标准
- •Any investigational agents within 28 days prior to the day of randomization.
- •Any 225Ac-based investigational compound used prior to the day of randomization.
- •Participants with a history of CNS metastases who are neurologically unstable, symptomatic, or receiving corticosteroids for the purpose of maintaining neurologic integrity.
- •Concurrent acute kidney injury (renal failure developed between 48 hours to 7 days) or chronic kidney disease (at least 3 months of ongoing renal injury)
- •Baseline xerostomia ≥ Grade 2 by CTCAE v.5
- •History of uncontrolled hypertension, myocardial infarction (MI), angina pectoris, or coronary artery bypass graft (CABG) within 6 months prior to ICF signature and/or clinically active significant cardiac disease
- •History of lymphoproliferative disease or any known malignancy or history of malignancy of any organ system within the past 2 years (except for basal cell carcinoma or actinic keratosis that have been treated with no evidence of recurrence in the past 3 months, non-invasive malignant colon polyps that have been removed).
- •Other protocol-defined inclusion/exclusion criteria may apply.
研究组 & 干预措施
Phase III: Investigator's choice of SoC
Participants will be given Standard of Care (SOC) treatment per Investigator's choice.
干预措施: Investigators choice of SoC (Drug)
Phase II: AAA817 Dose B
AAA817 will be given for a number of cycles; a cycle = 8 weeks
干预措施: AAA817 (Drug)
Phase II: AAA817 Dose A
AAA817 Dose A will be given for a number of cycles: a cycle = 8 weeks
干预措施: AAA817 (Drug)
Phase III: Recommended Phase 3 Dose of AAA817
Rp3D of AAA817 will be given for a number of cycles; a cycle = 8 weeks
干预措施: AAA817 (Drug)
结局指标
主要结局
Radiographic progression-free survival (rPFS)- Phase III
时间窗: from date of randomization up to approximately 24 months
Percentage of participants who are alive without radiographic progression or who are lost to follow-up at the time of analysis
Biochemical response rate (Phase II)
时间窗: from date of randomization up to approximately 24 months
Biochemical response rate as defined as the percentage of participants who achieved a ≥ 50% decrease from baseline that is confirmed by a second measurement
Adverse Events (AEs) and Serious Adverse Events (SAEs), and deaths - Phase II
时间窗: from day of randomization to 30 days after End of Treatment or (last AAA817 dose date + 55 days, last dose date of SoC + 30 days), whichever is later
Safety defined as the type, incidence and severity of AEs and SAEs, and deaths
Tolerability of the proposed dose of AAA817- Phase II
时间窗: From on-treatment period which start from the first dose of study treatment until 30 days post-last dose date for SoC and 55 days post last-dose for AAA817
Percentage of participants who experienced Dose interruptions, reductions, discontinuation, dose intensity and duration of exposure
Overall survival (OS)- Phase III
时间窗: from date of randomization up to approximately 24 months
Percentage of participants who are alive or who are lost to follow-up at the time of analysis
Biochemical response rate (Phase II)
时间窗: from date of randomization up to approximately 24 months
Biochemical response rate as defined as the percentage of participants who achieved a ≥ 50% decrease from baseline that is confirmed by a second measurement
Adverse Events (AEs) and Serious Adverse Events (SAEs), and deaths - Phase II
时间窗: from day of randomization to 30 days after End of Treatment or (last AAA817 dose date + 55 days, last dose date of SoC + 30 days), whichever is later
Safety defined as the type, incidence and severity of AEs and SAEs, and deaths
Tolerability of the proposed dose of AAA817- Phase II
时间窗: From on-treatment period which start from the first dose of study treatment until 30 days post-last dose date for SoC and 55 days post last-dose for AAA817
Percentage of participants who experienced Dose interruptions, reductions, discontinuation, dose intensity and duration of exposure
Radiographic progression-free survival (rPFS)- Phase III
时间窗: from date of randomization up to approximately 24 months
Percentage of participants who are alive without radiographic progression or who are lost to follow-up at the time of analysis
Overall survival (OS)- Phase III
时间窗: from date of randomization up to approximately 24 months
Percentage of participants who are alive or who are lost to follow-up at the time of analysis
次要结局
- Radiographic progression-free survival (rPFS)- Phase II(from date of randomization up to approximately 24 months)
- Progression free survival (PFS)- Phase II(from date of randomization up to approximately 24 months)
- Overall response rate (ORR)- Phase II(from date of randomization up to approximately 24 months)
- Disease control rate (DCR)- Phase II(from date of randomization up to approximately 24 months)
- Overall survival (OS)- Phase II(from date of randomization up to approximately 24 months)
- Progression free survival (PFS) -Phase III(from date of randomization up to approximately 24 months)
- Overall response rate (ORR)- Phase III(from date of randomization up to approximately 24 months)
- Disease control rate (DCR) -Phase III(from date of randomization up to approximately 24 months)
- Duration of response (DoR)- Phase III(from date of randomization up to approximately 24 months)
- Time to first radiographic soft tissue progression (TTSTP)- Phase III(from date of randomization up to approximately 24 months)
- First symptomatic skeletal event (TTSSE)_Phase III(from date of randomization up to approximately 24 months)
- Prostate specific antigen (PSA) response -Phase III(from date of randomization up to approximately 24 months)
- Patient reported disease related symptoms and health-related quality of life (HRQoL): Phase III(from date of randomization up to approximately 24 months)
- Radiographic progression-free survival (rPFS)- Phase II(from date of randomization up to approximately 24 months)
- Progression free survival (PFS)- Phase II(from date of randomization up to approximately 24 months)
- Overall response rate (ORR)- Phase II(from date of randomization up to approximately 24 months)
- Disease control rate (DCR)- Phase II(from date of randomization up to approximately 24 months)
- Overall survival (OS)- Phase II(from date of randomization up to approximately 24 months)
- Progression free survival (PFS) -Phase III(from date of randomization up to approximately 24 months)
- Overall response rate (ORR)- Phase III(from date of randomization up to approximately 24 months)
- Disease control rate (DCR) -Phase III(from date of randomization up to approximately 24 months)
- Duration of response (DoR)- Phase III(from date of randomization up to approximately 24 months)
- Time to first radiographic soft tissue progression (TTSTP)- Phase III(from date of randomization up to approximately 24 months)
- First symptomatic skeletal event (TTSSE)_Phase III(from date of randomization up to approximately 24 months)
- Prostate specific antigen (PSA) response -Phase III(from date of randomization up to approximately 24 months)
- Patient reported disease related symptoms and health-related quality of life (HRQoL): Phase III(from date of randomization up to approximately 24 months)
- Time to worsening on the Worst Pain: Phase III(from date of randomization up to approximately 24 months)