An Open-label Study Comparing Lutetium (177Lu) Vipivotide Tetraxetan (AAA617) in Combination With ARPI Versus AAA617 in PSMA Positive First-line mCRPC
NCT ID: NCT06894511
Last Updated: 2025-11-12
Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
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RECRUITING
PHASE2
420 participants
INTERVENTIONAL
2025-09-11
2029-04-09
Brief Summary
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Detailed Description
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Approximately 420 eligible participants will be randomized in a 1:1 ratio to one of the two treatment arms (Arm A: AAA617+ARPI vs Arm B: AAA617). The primary objective of the study is to evaluate the rPFS response in participants with metastatic CRPC, assessed by conventional imaging, treated with AAA617 in combination with ARPI and AAA617 alone. Best Supportive Care (BSC) will be allowed in both arms at the discretion of the investigator and includes available care for the eligible participants according to best institutional practice for mCRPC. Androgen deprivation therapy (ADT) is required in both arms.
A total of approximately 420 eligible participants will be 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 will be 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 \[BCR-non mHSPC or nmCRPC setting\]).
The study duration is approximately 3.5 years.
Conditions
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Keywords
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Study Design
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RANDOMIZED
PARALLEL
TREATMENT
NONE
Study Groups
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Arm A: AAA617 and ARPI
AAA617 and ARPI (Enzalutamide, Abiraterone):
* AAA617 will be administered once every 6 weeks (1 cycle) for a planned 6 cycles.
* ARPI will be administered from 14 days (+ 7 days) before first dose of AAA617 until participant is no longer clinically benefiting, or experiences unacceptable toxicity or if investigator determines that the patient should discontinue ARPI.
AAA617
Dose formulation: open-label vial
Dose level: 7.4 GBq (200 mCi) ± 10% Once, every 6 weeks for 6 cycles, intravenous administration
ARPI: Abiraterone
Dose formulation: tablet/capsule
Dose level: 160 mg (four 40 mg or two 80 mg soft capsules) as a single daily dose, oral administration
ARPI: Enzalutamide
Dose formulation: tablet
Dose level: 1000 mg daily (two 500 mg tablets or four 250 mg tablets as a single daily dose together with 5 mg oral prednisone 2 times a day, oral administration
Arm B: AAA617 alone
AAA617 alone: Control Arm B participants will receive a dose of AAA617 which will be administered once every 6 weeks (1 cycle) for a planned 6 cycles.
AAA617
Dose formulation: open-label vial
Dose level: 7.4 GBq (200 mCi) ± 10% Once, every 6 weeks for 6 cycles, intravenous administration
Interventions
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AAA617
Dose formulation: open-label vial
Dose level: 7.4 GBq (200 mCi) ± 10% Once, every 6 weeks for 6 cycles, intravenous administration
ARPI: Abiraterone
Dose formulation: tablet/capsule
Dose level: 160 mg (four 40 mg or two 80 mg soft capsules) as a single daily dose, oral administration
ARPI: Enzalutamide
Dose formulation: tablet
Dose level: 1000 mg daily (two 500 mg tablets or four 250 mg tablets as a single daily dose together with 5 mg oral prednisone 2 times a day, oral administration
Other Intervention Names
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Eligibility Criteria
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Inclusion Criteria
* 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.
Exclusion Criteria
* 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.
18 Years
100 Years
MALE
No
Sponsors
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Novartis Pharmaceuticals
INDUSTRY
Responsible Party
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Principal Investigators
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Novartis Pharmaceuticals
Role: STUDY_DIRECTOR
Novartis Pharmaceuticals
Locations
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Cancer And Blood Spclsts of AZ
Casa Grande, Arizona, United States
Highlands Oncology Group
Fayetteville, Arkansas, United States
Hoag Memorial Hospital Presbyterian
Newport Beach, California, United States
East Jefferson Hospital
Metairie, Louisiana, United States
Urology Cancer Center PC
Omaha, Nebraska, United States
Oregon Urology Institute
Springfield, Oregon, United States
Texas Oncology P A
Bedford, Texas, United States
Urology San Antonio
San Antonio, Texas, United States
Virginia Cancer Specialists
Fairfax, Virginia, United States
Countries
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Central Contacts
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Novartis Pharmaceuticals
Role: CONTACT
Facility Contacts
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Estrella Crystal
Role: primary
Shelly Farrow
Role: primary
Geo Raya
Role: primary
Antonia Eltit
Role: primary
Makenzie Ann Long
Role: primary
Helena McLeod
Role: primary
Carolina Hernandez
Role: primary
Manuel Hernandez
Role: primary
Hoang Anh Dinh
Role: primary
Other Identifiers
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CAAA617B1US01
Identifier Type: -
Identifier Source: org_study_id