An Open-label Study of Lutetium (177Lu) Vipivotide Tetraxetan (AAA617) in Combination With ARPI Versus AAA617 in PSMA Positive First-line mCRPC (PSMAndARPI)

April 27, 2026 updated by: Novartis Pharmaceuticals

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.

Study Overview

Status

Active, not recruiting

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

7

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Arizona
      • Casa Grande, Arizona, United States, 85122
        • Cancer And Blood Spclsts of AZ
      • Gilbert, Arizona, United States, 85297
        • Arizona Center for Cancer Care
    • California
      • Newport Beach, California, United States, 92663
        • Hoag Memorial Hospital Presbyterian
    • Florida
      • Jacksonville, Florida, United States, 32256
        • Cancer Specialists of North Florida
    • Nebraska
      • Omaha, Nebraska, United States, 68130
        • Urology Cancer Center PC

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Key Inclusion Criteria:

  • 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).

  • 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 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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Arm A: AAA617 and ARPI (Abiraterone or Enzalutamide)
4 participants to receive AAA617 in combination with ARPI
Drug: AAA617

Dose formulation: open-label vial

Dose level: 7.4 GBq (200 mCi) ± 10% Once, every 6 weeks for 6 cycles, intravenous administration

Other Names:
  • [177Lu]Lu-PSMA-617
  • 177Lu-PSMA-617
  • lutetium (177Lu) vipivotide tetraxetan
Drug: 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

Drug: ARPI: Abiraterone

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
Active Comparator: Arm B: AAA617 alone
3 participants will receive AAA617 alone.
Drug: AAA617

Dose formulation: open-label vial

Dose level: 7.4 GBq (200 mCi) ± 10% Once, every 6 weeks for 6 cycles, intravenous administration

Other Names:
  • [177Lu]Lu-PSMA-617
  • 177Lu-PSMA-617
  • lutetium (177Lu) vipivotide tetraxetan

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Safety: Number of participants with adverse events (AEs) and serious adverse events (SAEs)
Time Frame: up to end of study, approx. 1.5 years
Number of participants with adverse events (AEs) and serious adverse events (SAEs).
up to end of study, approx. 1.5 years

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Overall survival (OS)
Time Frame: From date of randomization to date of death due to any cause, up to approximately 24 months
Time to death due to any cause
From date of randomization to date of death due to any cause, up to approximately 24 months
Progression-free survival (PFS)
Time Frame: From date of randomization to date of first documented progression or death from any cause, whichever occurs first, up to approximately 24 months
Time to first documented progression or death from any cause per investigator's assessment (radiographic, clinical, or Prostate Specific Antigen (PSA) progression).
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
Time Frame: From date of randomization to first documented progression or death from any cause, whichever occurs first, for up to approximately 24 months
Time to first documented progression or death from any cause by investigator's assessment (radiographic progression, clinical progression, PSA progression) on next line of therapy
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)
Time Frame: From date of randomization to date of first documented progression or death due to any cause, whichever occurs first, up to approximately 24 months
The proportion of participants with best overall response (BOR) of confirmed complete response (CR) or partial response (PR) in soft tissue based on tumor response data per BICR assessment and according to PCWG3-modified RECIST v1.1, in the absence of bone progression as per PCWG3-modified RECIST v1.1. Additionally, ORR in soft tissue only according to PCWG3-modified RECIST v1.1 will be analyzed.
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)
Time Frame: From date of randomization to date of first documented progression or death due to any cause, whichever occurs first, up to approximately 24 months
The percentage of participants with best overall response (BOR) of confirmed complete response (CR), partial response (PR), stable disease (SD) or Non-CR/Non-progressive disease (PD) in soft tissue based on tumor response data per BICR assessment and according to PCWG3-modified RECIST v1.1, in the absence of bone progression as per PCWG3-modified RECIST v1.1
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)
Time Frame: 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
Time between the date of first documented response and the date of first documented radiographic progression or death due to any cause, according to PCWG3-modified RECIST v1.1, in the absence of bone progression as per PCWG3-modified, based on tumor response data per BICR.
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
Time Frame: From baseline to date of first documented progression or death due to any cause, whichever occurs first, up to approximately 24 months
The percentage of participants who achieved ≥ 50% and ≥ 90% decrease in PSA from baseline, respectively, that is confirmed by a second PSA measurement ≥4 weeks
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)
Time Frame: 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 to first new symptomatic skeletal event (symptomatic pathological bone fracture, spinal cord compression, tumor-related orthopedic surgical intervention, or requirement for radiation therapy to relieve bone pain) or death due to any cause, whichever occurs first, up to approximately 24 months.
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)
Time Frame: 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 radiographic soft tissue progression per soft tissue rules of PCWG3-modified RECIST v1.1 as assessed by BICR.
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
Time Frame: 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
Time to first documented dose of new cytotoxic chemotherapy being administered to the participant.
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)
Time Frame: From date of randomization to date of worsening of worst pain intensity, up to approximately 24 months
Time to worsening of worst pain intensity or death due to any cause. Worsening of worst pain intensity is defined as first occurring 1) an increase of worsening threshold compared to baseline, 2) clinical disease progression or 3) death.
From date of randomization to date of worsening of worst pain intensity, up to approximately 24 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Novartis Pharmaceuticals

Investigators

  • Study Director: Novartis Pharmaceuticals, Novartis Pharmaceuticals

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

September 11, 2025

Primary Completion (Estimated)

October 15, 2026

Study Completion (Estimated)

October 15, 2026

Study Registration Dates

First Submitted

March 18, 2025

First Submitted That Met QC Criteria

March 18, 2025

First Posted (Actual)

March 25, 2025

Study Record Updates

Last Update Posted (Actual)

May 1, 2026

Last Update Submitted That Met QC Criteria

April 27, 2026

Last Verified

April 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CAAA617B1US01

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

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.

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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