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

NCT ID: NCT06855277

Last Updated: 2025-11-12

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE3

Total Enrollment

605 participants

Study Classification

INTERVENTIONAL

Study Start Date

2025-07-01

Study Completion Date

2032-11-04

Brief Summary

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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) 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.

Detailed Description

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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 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) per investigator's choice. Treatment with ARPI should continue as per protocol end of treatment criteria. Treatment duration with taxane-based chemotherapy will 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.

Conditions

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Prostate Cancer

Keywords

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Positive Metastatic Castration Resistant Prostate Cancer PSMA PSMA-positive AAA817 [225AC] AC-PSMA-617 Radioligand Therapy RLT Androgen receptor pathway inhibitor ARPI Taxane Metastatic castration resistant prostate cancer mCRPC AcTFirst

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

DIAGNOSTIC

Blinding Strategy

NONE

Study Groups

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Investigational Arm: AAA817+ARPI (enzalutamide or abiraterone)

Participants will receive AAA817 infusion directly into a vein with ARPIs.

Group Type EXPERIMENTAL

AAA817

Intervention Type DRUG

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.

ARPI

Intervention Type DRUG

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.

Investigational Arm: AAA817

Participants will receive AAA817 infusion directly into a vein.

Group Type EXPERIMENTAL

AAA817

Intervention Type DRUG

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.

Control arm: Investigator's choice of SoC (ARPI or taxane-based chemotherapy)

Participants will receive standard treatment as decided by the trial doctor either as a chemotherapy infusion directly into a vein or ARPI either as capsules or tablets.

Group Type ACTIVE_COMPARATOR

ARPI

Intervention Type DRUG

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.

Standard of Care

Intervention Type DRUG

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.

Interventions

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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.

Intervention Type 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.

Intervention Type 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.

Intervention Type DRUG

Other Intervention Names

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[225Ac]Ac-PSMA-617 Enzalutamide or Abiraterone ARPI enzalutamide ARPI abiraterone Taxane based chemotherapy of docetaxel Taxane based chemotherapy of cabazitaxel

Eligibility Criteria

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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 or ARPI change 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).

Exclusion Criteria

* Previous treatment with any approved or investigational RLT, approved or investigational radioisotopes
* Previous treatment with any conventional external beam radiotherapy including hemi-body radiation within 6 weeks of randomization (within 2 weeks for radiotherapy of localized metastases).
* Participants with known or suspected deleterious germline or somatic homologous recombination repair (HRR) gene-mutated metastatic castration-resistant prostate cancer.
* Any approved or investigational agents/systemic anti-cancer therapy (e.g. other chemotherapy, investigational therapy, immunotherapy or biological therapy including monoclonal antibodies) within 28 days (or 5 times the half-life of that therapy whichever is longer) of the anticipated day C1D1.
* Diagnosed with other active malignancies that are expected to alter life expectancy or may interfere with disease assessment.
Minimum Eligible Age

18 Years

Maximum Eligible Age

100 Years

Eligible Sex

MALE

Accepts Healthy Volunteers

No

Sponsors

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Novartis Pharmaceuticals

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Novartis Pharmaceuticals

Role: STUDY_DIRECTOR

Novartis Pharmaceuticals

Locations

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University of Kansas Hospital

Kansas City, Kansas, United States

Site Status RECRUITING

Carolina Urologic Research Center

Myrtle Beach, South Carolina, United States

Site Status RECRUITING

Novartis Investigative Site

Darlinghurst, New South Wales, Australia

Site Status RECRUITING

Novartis Investigative Site

Adelaide, South Australia, Australia

Site Status RECRUITING

Novartis Investigative Site

Guangzhou, Guangdong, China

Site Status RECRUITING

Novartis Investigative Site

Wuhan, Hubei, China

Site Status RECRUITING

Novartis Investigative Site

Wuhan, Hubei, China

Site Status RECRUITING

Novartis Investigative Site

Nanjing, Jiangsu, China

Site Status RECRUITING

Novartis Investigative Site

Nanjing, Jiangsu, China

Site Status RECRUITING

Novartis Investigative Site

Shenyang, Liaoning, China

Site Status RECRUITING

Novartis Investigative Site

Chengdu, Sichuan, China

Site Status RECRUITING

Novartis Investigative Site

Beijing, , China

Site Status RECRUITING

Novartis Investigative Site

Guangzhou, , China

Site Status RECRUITING

Novartis Investigative Site

Shanghai, , China

Site Status RECRUITING

Novartis Investigative Site

Shanghai, , China

Site Status RECRUITING

Novartis Investigative Site

Shanghai, , China

Site Status RECRUITING

Novartis Investigative Site

Pokfulam, , Hong Kong

Site Status RECRUITING

Novartis Investigative Site

Sapporo, Hokkaido, Japan

Site Status RECRUITING

Novartis Investigative Site

Kobe, Hyōgo, Japan

Site Status RECRUITING

Novartis Investigative Site

Yokohama, Kanagawa, Japan

Site Status RECRUITING

Novartis Investigative Site

Chiba, , Japan

Site Status RECRUITING

Novartis Investigative Site

Fukuoka, , Japan

Site Status RECRUITING

Novartis Investigative Site

Kyoto, , Japan

Site Status RECRUITING

Novartis Investigative Site

Singapore, , Singapore

Site Status RECRUITING

Novartis Investigative Site

Singapore, , Singapore

Site Status RECRUITING

Novartis Investigative Site

Singapore, , Singapore

Site Status RECRUITING

Novartis Investigative Site

Kaohsiung City, , Taiwan

Site Status RECRUITING

Novartis Investigative Site

Taoyuan District, , Taiwan

Site Status RECRUITING

Novartis Investigative Site

Sutton, Surrey, United Kingdom

Site Status RECRUITING

Countries

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United States Australia China Hong Kong Japan Singapore Taiwan United Kingdom

Central Contacts

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Novartis Pharmaceuticals

Role: CONTACT

Phone: 1-888-669-6682

Email: [email protected]

Novartis Pharmaceuticals

Role: CONTACT

Phone: +41613241111

Facility Contacts

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Gloria Rodriguez

Role: primary

Kate Valipour

Role: primary

Other Identifiers

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2024-512340-32-00

Identifier Type: REGISTRY

Identifier Source: secondary_id

CAAA817B12301

Identifier Type: -

Identifier Source: org_study_id