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NCT07226986PHASE1, PHASE2Recruiting

A Phase Ib/II Open-label Study of AMO959 With Lutetium (177Lu) Vipivotide Tetraxetan (AAA617) in Combination With ARPI in Adult Participants With PSMA-positive mCRPC

Novartis Pharmaceuticals

Start Date

12/5/2025

Completion Date

9/13/2029

Summary

The purpose of this phase Ib/II study is to (a) in Phase Ib evaluate the safety, tolerability, and pharmacokinetics (PK) of AMO959 when given in combination with lutetium (177Lu) vipivotide tetraxetan (also known as \[177Lu\]Lu-PSMA-617 or 177Lu-PSMA-617 and hereafter referred to as AAA617) with an androgen receptor pathway inhibitor (ARPI) in participants with metastatic castration resistant prostate cancer (mCRPC) who have failed one prior ARPI and with or without prior taxane exposure, and (b) in Phase II evaluate the preliminary efficacy of AMO959 in combination with AAA617 and ARPI in participants with mCRPC who have failed one prior ARPI, but who have not yet been exposed to taxane treatment.

Detailed Description

This study will consist of two phases: 1. The escalation phase (Ib) will consist of provisionally three dose level cohorts of 3-6 participants investigating the safety, tolerability, and to determine the recommended dose for expansion (RDE) of AMO959 with standard dose of AAA617 +/- ARPI (abiraterone or enzalutamide). Initially AMO959 monotherapy will be administered, and then AMO959 will be given along with AAA617 in the same participants. Dose escalation meetings (DEMs) will occur when all participants in a dose level cohort have completed the DLT evaluation period or have experienced a DLT prior to the end of the evaluation period. 2. The Phase II will follow with 25 participants per arm randomized in a 1:1:1 ratio treated at the RDE(s) of AMO959 along with AAA617 and ARPI (abiraterone or enzalutamide) and AAA617 and ARPI (abiraterone or enzalutamide).

Eligibility Criteria

Age Range: 18 years to No maximum

Key Inclusion Criteria: * Signed informed consent must be obtained prior to participation in the study. * Participants must be adults ≥ 18 years of age. * Participants must have an ECOG performance status of 0 to 2. * Participants must have histologically confirmed adenocarcinoma of the prostate. Participants with other histology (e.g. neuroendocrine, intraductal subtype) are not eligible. * Phase Ib: Prior exposure of up to 1 line of taxane-based chemotherapy is permissible. Phase II: Participants must not have received taxane-based chemotherapy in mCRPC setting (allowed in mHSPC setting). * Participants must have PSMA-PET positive disease assessed by using a PSMA imaging agent that is approved as per protocol and are eligible as determined by the sponsor's central reading rules. * Castration level of testosterone (\< 50 ng/dL), and/or use of concomitant ADT * Participant must have been diagnosed with mCRPC with documented progressive disease while on treatment with ARPI in mHSPC or earlier 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). Key Exclusion Criteria: * Concurrent local (radiation therapy to the prostate with curative intent or other prostate antineoplastic ablative procedures) or systemic (hormonal ablation, chemotherapy, immunotherapy, , RLTs) antineoplastic treatments, or within 28 days of enrollment (Phase Ib) or randomization (Phase II) * Prior treatment with any RLT or PSMA-targeted agents (approved or investigational) * Any other investigational agents within 28 days prior to first dose of any study treatment * Concurrent serious medical conditions that may interfere with study procedures or followup * Participants with a history of CNS metastases must have received therapy (surgery, whole brain radiation therapy, stereotactic radiosurgery) and be neurologically stable, asymptomatic, and not taking corticosteroids for the purpose of maintaining neurologic integrity. Other protocol-defined inclusion/exclusion criteria may apply.

Interventions

DRUG

AMO959

RADIATION

AAA617

DRUG

Enzalutamide

DRUG

Abiraterone

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Conditions

PSMA-positive Metastatic Castration Resistant Prostate Cancer (mCRPC) With Prior Exposure to One Prior ARPI Who Are Candidates for Taxane-based Chemotherapy

Locations

VA Greater LA Healthcare System

Los Angeles, California 90073

United States

Rio Grande Urology

El Paso, Texas 79912

United States

Utah Intermountain Medical Center

Murray, Utah 84107

United States

Novartis Investigative Site

Malvern, Victoria 3144

Australia

Novartis Investigative Site

Melbourne, Victoria 3004

Australia

Novartis Investigative Site

Murdoch, Western Australia 6150

Australia

Novartis Investigative Site

Bordeaux, 33076

France

Novartis Investigative Site

Clermont-Ferrand, 63011

France

Novartis Investigative Site

Nantes, 44093

France

Novartis Investigative Site

Villejuif, 94800

France

Novartis Investigative Site

Dresden, Saxony 01307

Germany

Novartis Investigative Site

Essen, 45147

Germany

Novartis Investigative Site

München, 80377

Germany

Novartis Investigative Site

Cona, FE 44124

Italy

Novartis Investigative Site

Milan, MI 20133

Italy

Novartis Investigative Site

Naples, 80131

Italy

Novartis Investigative Site

Sapporo, Hokkaido 060-8648

Japan

Novartis Investigative Site

Granada, Andalusia 18014

Spain

Novartis Investigative Site

L'Hospitalet de Llobregat, Barcelona 08907

Spain

Novartis Investigative Site

Barcelona, 08036

Spain

Novartis Investigative Site

Madrid, 28041

Spain