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

NCT06855277 | Recruiting Phase 3 DMC FDA Drug

• 2 other identifiers: CAAA817B123012024-512340-32
• Study Type: interventional
• Target: 940
• Locations: 11 countries
• Sites: 55

Brief Summary

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.

Conditions

Prostate Cancer

Keywords

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; [177Lu]Lu- PSMA-617; AAA617

Outcome Measures

Primary Outcomes (1)

• Radiographic Progression Free Survival (rPFS)

  Time to radiographic disease progression or death due to any cause.

  From the date of randomization to the date of the first documented radiographic disease progression using conventional imaging, or death due to any cause, whichever occurs first, assessed up to approximately 40.0 months.

Secondary Outcomes (15)

• Overall Survival (OS) (Key Secondary Endpoint)

  From the date of randomization to the date of death due to any cause, assessed up to approximately 40 months.

• Radiographic Progression Free Survival by by Prostate Cancer Working Group 3 (PCWG3)-modified RECIST v1.1 (Key Secondary)

  From date of randomization to the date of the first documented radiographic disease progression or death due to any cause, whichever occurs first, assessed up to approximately 40.0 months.

• Overall Survival in participants with PSMA-positive mCRPC treated with another ARPI. (Key Secondary)

  From the date of randomization to the date of death due to any cause.

• rPFS in participants treated with AAA817

  From the date of randomization to the date of the first documented radiographic disease progression, or death due to any cause, whichever occurs first, assessed up to approximately 40.0 months.

• Progression Free Survival (PFS)

  From date of randomization to the first documented progression by investigator's assessment or death due to any cause, whichever occurs first, assessed up to approximately 40.0 months.

Study Arms (3)

Investigational Arm: AAA817+ARPI (enzalutamide or abiraterone)

EXPERIMENTAL

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

Drug: AAA817; Drug: ARPI

Investigational Arm: AAA817

EXPERIMENTAL

Participants will receive AAA817 infusion directly into a vein.

Drug: AAA817

Control arm: Investigator's choice of SoC (ARPI or chemotherapy or AAA617)

ACTIVE COMPARATOR

Participants will receive standard treatment as decided by the trial doctor either as a taxane-based chemotherapy infusion directly into a vein or ARPI change either as capsules or tablets or AAA617 monotherapy infusion directly into a vein.

Drug: ARPI; Drug: Standard of Care

Interventions

AAA817 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.

Also known as: [225Ac]Ac-PSMA-617

Investigational Arm: AAA817; Investigational Arm: AAA817+ARPI (enzalutamide or abiraterone)

ARPI 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.

Also known as: Enzalutamide or Abiraterone

Control arm: Investigator's choice of SoC (ARPI or chemotherapy or AAA617); Investigational Arm: AAA817+ARPI (enzalutamide or abiraterone)

Standard of Care 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 or \[177Lu\]Lu-PSMA-617 (AAA617).

Also known as: ARPI enzalutamide, ARPI abiraterone, Taxane based chemotherapy of docetaxel, Taxane based chemotherapy of cabazitaxel, [177Lu]Lu-PSMA-617 (AAA617)

Control arm: Investigator's choice of SoC (ARPI or chemotherapy or AAA617)

Eligibility Criteria

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

You may qualify if:

• 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.

You may not qualify if:

• Previous anti-cancer treatment with any approved or investigational radiopharmaceuticals (for example, \[177Lu\]Lu-PSMA, \[177Lu\]-DOTA, or Radium- 223.)
• Previous treatment with any external beam radiotherapy including hemi-body radiation within 6 weeks of randomization (within 2 weeks for radiotherapy of localized metastases).
• Any prior PARP inhibitor or other systemic anticancer therapy administered for metastatic castration-resistant prostate cancer (mCRPC). Any other approved or investigational systemic therapy (including chemotherapy, immunotherapy, biologics, or monoclonal antibodies) is prohibited within 28 days or 5 half-lives (whichever is shorter) before randomization.
• Note: Prior ARPI administered in the mHSPC setting or earlier may continue until C1D1.

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (55)

Sansum Clinic

Santa Barbara, California, 93105, United States

RECRUITING

Rocky Mountain Cancer Centers

Denver, Colorado, 80218, United States

RECRUITING

Miami Cancer Institute at Bapt

Miami, Florida, 33173, United States

RECRUITING

AdventHealth

Orlando, Florida, 32804, United States

RECRUITING

Univ Of Iowa Hospitals And Clinics

Iowa City, Iowa, 52242, United States

RECRUITING

University of Kansas Hospital

Kansas City, Kansas, 66160, United States

RECRUITING

Wash U School of Medicine

St Louis, Missouri, 63110, United States

RECRUITING

Bassett Medical Center

Cooperstown, New York, 13326, United States

RECRUITING

Weill Cornell Medicine NY-Presb

New York, New York, 10021, United States

RECRUITING

University of Rochester Medical Ctr

Rochester, New York, 14642, United States

RECRUITING

Associated Med Professionals of NY

Syracuse, New York, 13210, United States

RECRUITING

Carolina Urologic Research Center

Myrtle Beach, South Carolina, 29572, United States

RECRUITING

Urology San Antonio

San Antonio, Texas, 78229, United States

RECRUITING

Swedish Medical Center

Seattle, Washington, 98122-4379, United States

RECRUITING

Medical College of Wisconsin

Milwaukee, Wisconsin, 53226, United States

RECRUITING

Novartis Investigative Site

Darlinghurst, New South Wales, 2010, Australia

RECRUITING

Novartis Investigative Site

Adelaide, South Australia, 5000, Australia

RECRUITING

Novartis Investigative Site

São Paulo, São Paulo, 01308-050, Brazil

RECRUITING

Novartis Investigative Site

São Paulo, São Paulo, 05652-000, Brazil

RECRUITING

Novartis Investigative Site

Guangzhou, Guangdong, 510632, China

RECRUITING

Novartis Investigative Site

Wuhan, Hubei, 430022, China

RECRUITING

Novartis Investigative Site

Wuhan, Hubei, 430030, China

RECRUITING

Novartis Investigative Site

Nanjing, Jiangsu, 210006, China

RECRUITING

Novartis Investigative Site

Nanjing, Jiangsu, 210029, China

RECRUITING

Novartis Investigative Site

Shenyang, Liaoning, 110011, China

RECRUITING

Novartis Investigative Site

Chengdu, Sichuan, 610041, China

RECRUITING

Novartis Investigative Site

Hangzhou, Zhejiang, 310022, China

RECRUITING

Novartis Investigative Site

Beijing, 100034, China

RECRUITING

Novartis Investigative Site

Beijing, 100036, China

RECRUITING

Novartis Investigative Site

Guangzhou, 510060, China

RECRUITING

Novartis Investigative Site

Shanghai, 200025, China

RECRUITING

Novartis Investigative Site

Shanghai, 200032, China

RECRUITING

Novartis Investigative Site

Shanghai, 200127, China

RECRUITING

Novartis Investigative Site

Hong Kong, 999077, Hong Kong

RECRUITING

Novartis Investigative Site

Hong Kong, 999999, Hong Kong

RECRUITING

Novartis Investigative Site

Gurgaon, Haryana, 122 002, India

RECRUITING

Novartis Investigative Site

Mumbai, Maharashtra, 400 012, India

RECRUITING

Novartis Investigative Site

Sapporo, Hokkaido, 0608648, Japan

RECRUITING

Novartis Investigative Site

Kobe, Hyōgo, 6500047, Japan

RECRUITING

Novartis Investigative Site

Yokohama, Kanagawa-ku, 236-0004, Japan

RECRUITING

Novartis Investigative Site

Chuo Ku, Tokyo, 1040045, Japan

RECRUITING

Novartis Investigative Site

Chiba, 260-8717, Japan

RECRUITING

Novartis Investigative Site

Fukuoka, 811-0213, Japan

RECRUITING

Novartis Investigative Site

Fukuoka, 812-0033, Japan

RECRUITING

Novartis Investigative Site

Fukuoka, 8128582, Japan

RECRUITING

Novartis Investigative Site

Hiroshima, 7348551, Japan

RECRUITING

Novartis Investigative Site

Kyoto, 6068507, Japan

RECRUITING

Novartis Investigative Site

Singapore, 119074, Singapore

RECRUITING

Novartis Investigative Site

Singapore, 168583, Singapore

RECRUITING

Novartis Investigative Site

Singapore, 169608, Singapore

RECRUITING

Novartis Investigative Site

Seoul, Korea, 03080, South Korea

RECRUITING

Novartis Investigative Site

Seoul, 06351, South Korea

RECRUITING

Novartis Investigative Site

Kaohsiung City, 83301, Taiwan

RECRUITING

Novartis Investigative Site

Taoyuan District, 33305, Taiwan

RECRUITING

Novartis Investigative Site

Sutton, Surrey, SM2 5PT, United Kingdom

RECRUITING

MeSH Terms

Conditions

Prostatic Neoplasms

Interventions

(225)Ac-PSMA-617; enzalutamide; abiraterone; Standard of Care

Condition Hierarchy (Ancestors)

Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Quality Indicators, Health Care; Quality of Health Care; Health Services Administration; Health Care Quality, Access, and Evaluation

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY DIRECTOR

Central Study Contacts

Novartis Pharmaceuticals

CONTACT

1-888-669-6682; novartis.email@novartis.com

Novartis Pharmaceuticals

CONTACT

+41613241111

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 18, 2025
• First Posted: March 3, 2025
• Study Start: July 1, 2025
• Primary Completion (Estimated): September 29, 2028
• Study Completion (Estimated): November 4, 2032
• Last Updated: February 24, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will share

Locations

HK (2); SG (3); GB (1); TW (2); AU (2); BR (2); KR (2); JP (10); IN (2); CN (14); US (15)