Metastatic Castration Resistant Prostate Cancer (mCRPC)Phase 2PSMAndARPINCT06894511
An Open-label Study of Lutetium (177Lu) Vipivotide Tetraxetan (AAA617) in Combination With ARPI Versus AAA617 in PSMA Positive First-line mCRPC
A Phase 2 study testing AAA617, ARPI: Abiraterone and ARPI: Enzalutamide in people with Metastatic Castration Resistant Prostate Cancer (mCRPC), run by Novartis Pharmaceuticals at 5 sites in United States.
Trial summary
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… Read more about this study
- Who is it for?
- Ages 18 to 100 years, men only
- Conditions the study is for
- Metastatic Castration Resistant Prostate Cancer (mCRPC)
- What is being tested?
- AAA617, ARPI: Abiraterone and ARPI: Enzalutamide
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 7 participants
- Where
- 5 sitesUnited States
- Study dates
- 11 Sep 2025to 15 Oct 2026
- Phase
- Phase 2
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 100 years
- Men only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Participants must have an ECOG performance status of 0 to 2.
- 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).
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- 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.
Who cannot join
- 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.
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- 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.
Trial locations and contacts
5 sites in 1 country.
5 sites in 1 country
United States5 sites
Cancer And Blood Spclsts of AZ
Casa Grande, Arizona, 85122
Arizona Center for Cancer Care
Gilbert, Arizona, 85297
Cancer Specialists of North Florida
Jacksonville, Florida, 32256
Hoag Memorial Hospital Presbyterian
Newport Beach, California, 92663
Urology Cancer Center PC
Omaha, Nebraska, 68130
About this study
Official title: 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)
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.
Read the detailed description
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.
- Being tested
- AAA617, ARPI: Abiraterone, ARPI: Enzalutamide
- Keywords
- Prostate-specific membrane antigen (PSMA), PSMA, PSMA positive first-line mCRPC, lutetium (177Lu) vipivotide tetraxetan, AAA617, Androgen Receptor Pathway Inhibitors (ARPI), ARPI, Enzalutamide, Darolutamide, Apalutamide, Abiraterone, mCRPC
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AAA617Drug
Also called lutetium (177Lu) vipivotide tetraxetan, [177Lu]Lu-PSMA-617, 177Lu-PSMA-617
Dose formulation: open-label vial
Dose level: 7.4 GBq (200 mCi) ± 10% Once, every 6 weeks for 6 cycles, intravenous administration
ARPI: AbirateroneDrug
Dose formulation: tablet/capsule
Dose level: 160 mg (four 40 mg soft capsules or four 40 mg tablets or two 80 mg tablets) as a single daily dose, oral administration
ARPI: EnzalutamideDrug
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
| Study group | Role | What they receive |
|---|---|---|
| Arm A: AAA617 and ARPI (Abiraterone or Enzalutamide) | Experimental | 4 participants to receive AAA617 in combination with ARPI Receives: Drug: AAA617; Drug: ARPI: Abiraterone; Drug: ARPI: Enzalutamide |
| Arm B: AAA617 alone | Active comparator | 3 participants will receive AAA617 alone. Receives: Drug: AAA617 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Safety: Number of participants with adverse events (AEs) and serious adverse events (SAEs)
Number of participants with adverse events (AEs) and serious adverse events (SAEs).
Measured: up to end of study, approx. 1.5 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Mar 2025
- Study start11 Sep 2025
- Primary completion15 Oct 2026 (estimated)
- Study completion15 Oct 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Metastatic Castration Resistant Prostate Cancer (mCRPC)Studies of the same condition, open and under way.
- More trials run by Novartis PharmaceuticalsThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 7 participants (actual)
Sponsor and investigators
- Lead sponsor
- Novartis Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Novartis Pharmaceuticals, Study director, Novartis Pharmaceuticals
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06894511
- Sponsor's protocol ID
- CAAA617B1US01
- Acronym
- PSMAndARPI
- Status last verified
- Oct 2026
- First submitted
- 18 Mar 2025
- Last updated
- 21 Oct 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent expert panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations. This trial data is currently available according to the process described on www.clinicalstudydatarequest.com.