Study Comparing AAA817+ARPI Versus Standard of Care in Adult Participants With PSMA-positive mCRPC

Last Update: Jun 10, 2026

A Phase III, Open-label, Multi-center, Randomized Study Comparing AAA817+ARPI Versus Standard of Care in Adult Participants With PSMA-positive Metastatic Castration Resistant Prostate Cancer

ClinicalTrials.gov Identifier:

NCT06855277

Novartis Reference Number:CAAA817B12301

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All compounds are either investigational or being studied for (a) new use(s). Efficacy and safety have not been established. There is no guarantee that they will become commercially available for the use(s) under investigation.

Study Description

The purpose of this study is to determine whether \[225Ac\]Ac-PSMA-617 (AAA817), given for up to 6 cycles at a dose of 10 Megabecquerel (MBq) +/- 10%, plus androgen receptor pathway inhibitor (ARPI), improves the radiographic progression free survival (rPFS) compared to investigator's choice of standard of care (SOC) (ARPI change or taxane-based chemotherapy or \[177Lu\]Lu-PSMA-617 (AAA617)) in adult participants with PSMA-positive metastatic castration resistant prostate cancer (mCRPC) treated with another ARPI as last treatment and who have not been exposed to a taxane-containing chemotherapy in the mCRPC setting nor have received any prior PSMA-targeting radioligand therapy. This is a phase III, open label, multicenter randomized study. The study aims at evaluating the superiority of 225Ac-PSMA-617 combined with androgen receptor pathway inhibitor (ARPI) over a change of ARPI or chemotherapy or \[177Lu\]Lu-PSMA-617 (AAA617) in prolonging progression free survival (rPFS).

Screening period: At screening, the participants will be assessed for eligibility and will undergo a positron emission tomography (PET)/computed tomography (CT) scan to evaluate PSMA positivity. Only participants with PSMA positive cancer and confirmed eligibility criteria will be randomized.

Participants randomized to the investigational arms will receive up to 6 doses of AAA817 10 Mbq +/- 10% given intravenously with or without an ARPI (oral enzalutamide or oral abiraterone) per investigator's choice. Treatment with ARPI should continue as per protocol end of treatment criteria.

Participants randomized to SoC will be treated with an ARPI change (oral enzalutamide or oral abiraterone) or taxane-based chemotherapy (docetaxel or cabazitaxel) or \[177Lu\]Lu-PSMA-617 (AAA617)' per investigator's choice. Treatment with ARPI should continue as per protocol end of treatment criteria. Treatment duration with taxane-based chemotherapy or AAA617will depend on the chosen regimen per the investigator's discretion following local guidelines as per standard of care and product labels and adhere to the protocol end of treatment criteria.

Supportive care will be allowed in both arms at the discretion of the investigator and includes available care for the eligible participant according to best institutional practice for mCRPC treatment, including androgen deprivation therapy (ADT).

Safety will be assessed routinely during the study. Crossover is not allowed among study arms.

The study will be conducted in the USA among other countries globally.

Condition

Prostate Cancer

Phase

Phase3

Overall Status

Recruiting

Number of Participants

940

Start Date

Jul 01, 2025

Completion Date

Nov 04, 2032

Gender

Male

Age(s)

18 Years - 100 Years (Adult, Older Adult)

Interventions

Drug

AAA817

AAA817 is being studied for treating PSMA positive mCRPC. Inside the body, it attaches itself to PSMA on the cell surface of the prostate cancer cells and emits radiation to kill them. This treatment is also called a radioligand therapy.

Drug

ARPI

Androgen receptor pathway inhibitor (ARPI): An ARPI is approved for the treatment of prostate cancer. It works by blocking signals from male hormones, such as testosterone, that helps cancer cells grow. By blocking these signals, an ARPI slows down or stops the growth of prostate cancer cells. In this trial, participants will be given either enzalutamide or abiraterone.

Drug

Standard of Care

Standard treatment includes approved treatment for mCRPC. In this trial, the trial doctor will decide which available treatment participants will receive. The trial doctor will select either an ARPI of enzalutamide or abiraterone, or a taxane based chemotherapy of docetaxel or cabazitaxel or \[177Lu\]Lu-PSMA-617 (AAA617).

Eligibility Criteria

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 histological, and/or cytological confirmation of adenocarcinoma of the prostate. Participants with mixed histology (neuroendocrine) are not eligible.
* Participants who have received taxane-based chemotherapy in mHSPC setting are eligible if they are deemed appropriate for chemotherapy, ARPI change or AAA617 as the next line of therapy in the opinion of the Investigator. Note: Participants who have received taxane-based chemotherapy for mCRPC are excluded.
* Participants must not have received taxane-based chemotherapy in mCRPC setting (allowed in mHSPC setting).
* Participants must have PSMA-PET positive disease using a PSMA imaging agent that is approved as per protocol.
* 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).

* Participants with deleterious or suspected deleterious germline or somatic homologous recombination repair (HRR) gene-mutated metastatic castration-resistant prostate cancer, as per local testing, may be enrolled if they had prior exposure to PARPi.

Recruiting

Palo Alto,California,94304,United States

Study Comparing AAA817+ARPI Versus Standard of Care in Adult Participants With PSMA-positive mCRPC

Study Description

Interventions

AAA817

ARPI

Standard of Care

Eligibility Criteria

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Stanford University Medical Center

Hong Song

Tiffany Chen

Northwestern University

Maha Hussain

Rachel Hanna Springsdorf

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Dana Farber Cancer Institute

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Xiao Wei

Nebraska Cancer Specialists

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Samuel Mehr

New Jersey Urology LLC

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Gordon Brown

Montefiore Medical Center

Benjamin A Gartrell

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MUSC Hollings Cancer Center