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

NCT06894511 | Active Not Recruiting Phase 2 FDA Drug

• 1 other identifier: CAAA617B1US01
• Study Type: interventional
• Target: 7
• Locations: 1 country
• Sites: 5

Brief 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 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.

Conditions

Metastatic Castration Resistant Prostate Cancer (mCRPC)

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

Outcome Measures

Primary Outcomes (1)

• 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).

  up to end of study, approx. 1.5 years

Study Arms (2)

Arm A: AAA617 and ARPI (Abiraterone or Enzalutamide)

EXPERIMENTAL

4 participants to receive AAA617 in combination with ARPI

Drug: AAA617; Drug: ARPI: Abiraterone; Drug: ARPI: Enzalutamide

Arm B: AAA617 alone

ACTIVE COMPARATOR

3 participants will receive AAA617 alone.

Drug: AAA617

Interventions

AAA617 DRUG

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

Also known as: lutetium (177Lu) vipivotide tetraxetan, [177Lu]Lu-PSMA-617, 177Lu-PSMA-617

Arm A: AAA617 and ARPI (Abiraterone or Enzalutamide); Arm B: AAA617 alone

ARPI: Abiraterone DRUG

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

Arm A: AAA617 and ARPI (Abiraterone or Enzalutamide)

ARPI: Enzalutamide DRUG

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 A: AAA617 and ARPI (Abiraterone or Enzalutamide)

Eligibility Criteria

• Age: 18 Years - 100 Years
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (5)

Cancer And Blood Spclsts of AZ

Casa Grande, Arizona, 85122, United States

Location

Arizona Center for Cancer Care

Gilbert, Arizona, 85297, United States

Location

Hoag Memorial Hospital Presbyterian

Newport Beach, California, 92663, United States

Location

Cancer Specialists of North Florida

Jacksonville, Florida, 32256, United States

Location

Urology Cancer Center PC

Omaha, Nebraska, 68130, United States

Location

MeSH Terms

Interventions

Lutetium; Lutetium-177; Pluvicto

Intervention Hierarchy (Ancestors)

Lanthanoid Series Elements; Metals, Rare Earth; Elements; Inorganic Chemicals; Transition Elements; Metals

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 18, 2025
• First Posted: March 25, 2025
• Study Start: September 11, 2025
• Primary Completion (Estimated): October 15, 2026
• Study Completion (Estimated): October 15, 2026
• Last Updated: May 1, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will share

Locations

US (5)