A Phase II, Open-label, Multi-Center, Randomized Study of Combination of Lutetium (177Lu) Vipivotide Tetraxetan (AAA617) and Androgen Receptor Pathway Inhibitor (ARPI) vs. Lutetium (177Lu) Vipivotide Tetraxetan (AAA617) in First-line Treatment of Patients With Prostate-Specific Membrane Antigen (PSMA)-Positive Progressive 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
- 7
- 试验地点
- 18
- 主要终点
- Safety: Number of participants with adverse events (AEs) and serious adverse events (SAEs)
研究概览
简要总结
The purpose of this study is to assess safety of combination of AAA617 (administered for 6 cycles at a dose of 7.4 GBq (200 mCi) +/- 10%) and ARPI and AAA617 alone in PSMA-positive mCRPC patients who were previously treated and progressed on ARPI in the biochemical recurrence (BCR)-non metastatic hormone sensitive prostate cancer (mHSPC), mHSPC, or non-metastatic Castration Resistant Prostate Cancer (nmCRPC) setting and have not previously received a taxane-containing regimen in the metastic castrate resistant prostate cancer (mCRPC) setting.
详细描述
This prospective, open-label, multi-center, randomized phase II study enrolled adult participants with PSMA PET (positron emission tomography) positive mCRPC who were previously treated and progressed on ARPI in the BCR-non mHSPC, mHSPC, or nmCRPC setting and have not previously received a taxane-containing regimen in the mCRPC setting. A PSMA PET/ computed tomography (CT) scan was done at Screening to confirm PSMA positive disease. This is a United States-based study.
Eligible participants were randomized in a 1:1 ratio to one of the two treatment arms (Arm A: AAA617+ARPI vs Arm B: AAA617). As the study is being closed out early, safety and tolerability will be assessed in already enrolled participants, treated with AAA617 in combination with ARPI or AAA617 alone. In Arm A, participants will receive ARPI between Day -14 and prior to first dose of AAA617 and will continue until a maximum of Cycle 6 Day 42 of AAA617, until the treatment is no longer clinically beneficial to participant, or experiences unacceptable toxicity or as per investigator's decision, whichever is earliest. The ARPI (abiraterone or enzalutamide) was as per investigator's choice, and switching from prior ARPI (pre-randomization) was highly recommended.
Seven eligible participants were randomized in a 1:1 ratio into one of two treatment arms. Participants in Arm A will receive AAA617 in combination with ARPI, while those in Arm B will receive AAA617 alone. Randomization was stratified by type of prior ARPI (abiraterone vs other [enzalutamide, apalutamide, or darolutamide]) and by setting of prior ARPI (mHSPC without docetaxel vs mHSPC with docetaxel vs others [BCRnon mHSPC or nmCRPC setting]).
The study duration is approximately 1.5 years.
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
- •Participants must have an ECOG performance status of 0 to
- •Participants must have histopathological, and/or cytological confirmation of adenocarcinoma of the prostate.
- •Participants must have PSMA PET positive disease using FDA approved PSMA-imaging approved agents, and eligible as determined by the sponsor's central reading rules.
- •Participants must have a castrate level of serum/plasma testosterone (< 50 ng/dL or < 1.7 nmol/L).
- •Newly diagnosed mCRPC participants who must have progression on prior ARPI in the BCR-non mHSPC, mHSPC, or nmCRPC setting.
- •Participants must have progressed only once on prior second-generation ARPI (abiraterone, enzalutamide, darolutamide, or apalutamide). First generation androgen receptor inhibitor therapy (e.g. bicalutamide) is allowed but not considered as prior ARPI therapy (second generation ARPI must be the most recent therapy received).
- •Participant must have been diagnosed with mCRPC with documented progressive disease after having been previously treated with ARPI in the BCR-non mHSPC, mHSPC, or nmCRPC setting as their last treatment (and did not progress on more than one ARPI), based on at least 1 of the following criteria:
- •Serum/plasma PSA progression is defined as 2 increases in PSA measured at least 1 week apart. The minimal start value is 2.0 ng/mL; 1.0 ng/mL is the minimal starting value if confirmed rise in PSA is the only indication of progression as per PCWG3 guidelines.
- •Soft-tissue progression defined [PCWG3-modified RECIST v1.1 (Eisenhauer et al 2009, Scher et al 2016)].
- •Progression of bone disease: 2 new lesions; only positivity on the bone scan defines metastatic disease to bone (PCWG3 criteria [Scher et al 2016]).
- •Participants must have ≥ 1 metastatic lesion by conventional imaging that is present at Screening/Baseline CT, MRI, or bone scan imaging obtained ≤ 28 days (about 4 weeks) prior to randomization.
- •Participants must have adequate organ function:
- •Bone marrow reserve
- •Absolute Neutrophil Count (ANC) ≥ 1.5 × 109/L
- •Platelets ≥ 100 × 109/L
- •Hemoglobin ≥ 9 g/dL Hepatic
- •Total bilirubin < 2 × the institutional upper limit of normal (ULN). For participants with known Gilbert's Syndrome ≤ 3 × ULN is permitted.
- •Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) ≤ 3.0 × ULN OR ≤ 5.0 × ULN for participants with liver metastases
- •Albumin ≥ 2.5 g/dL Renal
- •eGFR ≥ 50 mL/min/1.73m2 using Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation.
排除标准
- •Previous treatment with any of the following within 6 weeks of randomization: Strontium-89, Samarium-153, Rhenium-186, Rhenium-188, Radium-223, hemi-body irradiation, and Lu-DOTA radioligand therapy.
- •Previous PSMA-imaging RLT
- •Previous treatment with taxane-based chemotherapy at mCRPC settings. Taxane exposure is allowed in the mHSPC setting if more than 12 months have elapsed since the completion of this therapy.
- •Participants with a history of CNS metastases who are neurologically unstable, symptomatic, or receiving corticosteroids for the purpose of maintaining neurologic integrity.
- •Symptomatic cord compression, or clinical or radiologic findings indicative of impending cord compression.
- •Participant with known or suspected deleterious germline or somatic homologous recombination repair gene-mutated mCRPC, who is considered appropriate for treatment with PARP inhibitor according to the judgment of the investigator.
- •History of myocardial infarction, angina pectoris, or coronary artery bypass graft (CABG) within 6 months prior to ICF signature and/or clinically active significant cardiac disease
- •Concurrent serious acute or chronic nephropathy as determined by the principal investigator.
- •Other protocol-defined inclusion/exclusion criteria may apply.
研究组 & 干预措施
Arm B: AAA617 alone
3 participants will receive AAA617 alone.
干预措施: AAA617 (Drug)
Arm A: AAA617 and ARPI (Abiraterone or Enzalutamide)
4 participants to receive AAA617 in combination with ARPI
干预措施: AAA617 (Drug)
Arm A: AAA617 and ARPI (Abiraterone or Enzalutamide)
4 participants to receive AAA617 in combination with ARPI
干预措施: ARPI: Abiraterone (Drug)
Arm A: AAA617 and ARPI (Abiraterone or Enzalutamide)
4 participants to receive AAA617 in combination with ARPI
干预措施: ARPI: Enzalutamide (Drug)
结局指标
主要结局
Safety: Number of participants with adverse events (AEs) and serious adverse events (SAEs)
时间窗: up to end of study, approx. 1.5 years
Number of participants with adverse events (AEs) and serious adverse events (SAEs).
Radiographic Progression Free Survival (rPFS)
时间窗: From date of randomization to date of first documented radiographic disease progression or death due to any cause, whichever occurs first, up to approximately 24 months
Time to radiographic disease progression or death due to any cause as assessed by Blinded Independent Central review (BICR) using conventional imaging and PCWG3-modified RECIST v1.1 criteria.
次要结局
- Overall survival (OS)(From date of randomization to date of death due to any cause, up to approximately 24 months)
- Progression-free survival (PFS)(From date of randomization to date of first documented progression or death from any cause, whichever occurs first, up to approximately 24 months)
- Secondary PFS2(From date of randomization to first documented progression or death from any cause, whichever occurs first, for up to approximately 24 months)
- Overall response rate (ORR)(From date of randomization to date of first documented progression or death due to any cause, whichever occurs first, up to approximately 24 months)
- Disease control rate (DCR)(From date of randomization to date of first documented progression or death due to any cause, whichever occurs first, up to approximately 24 months)
- Duration of response (DoR)(From date of first documented response (CR or PR) and date of first documented radiographic progression in soft tissue or death due to any cause, whichever occurs first, up to approximately 24 months)
- Biochemical response by prostate specific antigen (PSA50 and PSA90) response rate(From baseline to date of first documented progression or death due to any cause, whichever occurs first, up to approximately 24 months)
- Time of first symptomatic skeletal event (TTSSE)(From date of randomization to date of first symptomatic skeletal event or death due to any cause, whichever occurs first, up to approximately 24 months)
- Time of first radiographic soft tissue progression (TTSTP)(From date of randomization to date of radiographic soft tissue progression or death due to any cause, whichever occurs first, up to approximately 24 months)
- Time to initiation of cytotoxic chemotherapy(From date of randomization to date of first documented dose of new cytotoxic chemotherapy or death due to any cause, whichever occurs first, up to approximately 24 months)
- Brief Pain Inventory-Short Form (BPI-SF)(From date of randomization to date of worsening of worst pain intensity, up to approximately 24 months)