Recruiting

Phase 3

Ac-PSMA-617 with ARPIStudy Comparing AAA817+ARPI Versus Standard of Care in Adult Participants With PSMA-positive mCRPC

Sponsor:

Novartis Pharmaceuticals

Code:

NCT06855277

Conditions

Prostate Cancer

Eligibility Criteria

Sex: Male

Age: 18 - 70+

Healthy Volunteers: Not accepted

Interventions

AAA817

ARPI

Standard of Care

Study Details

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

Study ID

NCT06855277

Start date

Jul 1, 2025

Status verified date

Aug, 2026

Completion date

Nov 4, 2032

Anticipated

Primary completion date

Sep 29, 2028

Anticipated

Eligibility Criteria

Sex: Male

Age: 18 - 70+

Healthy Volunteers: Not accepted

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.

Key Exclusion Criteria:

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.

Other protocol-defined inclusion/exclusion criteria may apply.

Study Design

Enrollment

940 participants

Anticipated

Allocation

Randomized

Intervention Model

Parallel Assignment

Primary purpose

Diagnostic

Interventions and Outcome Measures

Arms

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

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

experimental: Investigational Arm: AAA817

Participants will receive AAA817 infusion directly into a vein.

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

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.

Interventions

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.

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.

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).

Primary outcome measure

Radiographic Progression Free Survival (rPFS) [ Time Frame: 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. ]

Central Contacts and Locations

Central contacts

Novartis Pharmaceuticals

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

Novartis Pharmaceuticals

+41613241111

Locations

Urology Centers Of Alabama Pc

Recruiting

Homewood, Alabama, United States, 35209

Contacts

Meredith Sharpton

msharpton@urologyal.com

Principal Investigator:

Bryant Poole

Stanford University Medical Center

Recruiting

Palo Alto, California, United States, 94304

Contacts

Tiffany Chen

tiff1221@stanford.edu

Principal Investigator:

Hong Song

Sansum Clinic

Recruiting

Santa Barbara, California, United States, 93105

Contacts

Megan Martinez

805-563-5800 megan.martinez@sutterhealth.or

Principal Investigator:

Mukul Gupta

Rocky Mountain Cancer Centers

Recruiting

Denver, Colorado, United States, 80218

Contacts

Bethany Glatthar

303-839-6530 Bethany.Glatthar@usoncology.com

Principal Investigator:

Allen Cohn

Florida Cancer Specialists

Recruiting

Fort Myers, Florida, United States, 33901

Contacts

Julie Kara

jkara@flcancer.com

Principal Investigator:

Bradford Perez

Baptist Health South

Recruiting

Miami, Florida, United States, 33173

Contacts

Leslie Castaneda

leslie.castaneda@baptisthealth.net

Principal Investigator:

Rohan Garje

AdventHealth

Recruiting

Orlando, Florida, United States, 32804

Contacts

Joseph Guzzo

407-303-3235 joseph.guzzo@adventhealth.com

Principal Investigator:

Ravi Shridhar

University Cancer and Blood Center LLC

Recruiting

Athens, Georgia, United States, 30607

Contacts

Mary Egan

706-353-2990 mary.egan@universitycancer.com

Principal Investigator:

Gordon Schoenfeld

Northwestern University

Recruiting

Chicago, Illinois, United States, 60611

Contacts

Rachel Hanna Springsdorf

+1 312 695 1382 rachelspringsdorf@northwestern.edu

Principal Investigator:

Maha Hussain

University of Illinois Cancer Center at Chicago

Recruiting

Chicago, Illinois, United States, 60612

Contacts

Ethan Gu

312-413-2746 egu3@uic.edu

Principal Investigator:

Natalie Reizine

Univ Of Iowa Hospitals And Clinics

Recruiting

Iowa City, Iowa, United States, 52242

Contacts

Kellie Bodeker

kellie-bodeker@uiowa.edu

Principal Investigator:

Kristin Plichta

University of Kansas Hospital

Recruiting

Kansas City, Kansas, United States, 66160

Contacts

Collin Bruey

cbruey@kumc.edu

Principal Investigator:

Xinglei Shen

East Jefferson Hospital

Recruiting

Metairie, Louisiana, United States, 70006

Contacts

Alexandra Lieberman

alexandra.lieberman@lcmchealth.org

Principal Investigator:

Alton Oliver Sartor

Beth Israel Deaconess Med Center

Recruiting

Boston, Massachusetts, United States, 02215

Contacts

Katerina von Helms

617-667-7000 kvonhelm@bidmc.harvard.edu

Principal Investigator:

Glenn Bubley

Dana Farber Cancer Institute

Recruiting

Boston, Massachusetts, United States, 02215

Contacts

Amanda Lilienfeld

amanda_lilienfeld@dfci.harvard.edu

Principal Investigator:

Xiao Wei

Karmanos Cancer Institute

Recruiting

Detroit, Michigan, United States, 48201

Contacts

Kimberlee Dobson

313-576-9454 dobsonk@karmanos.org

Principal Investigator:

Nitin Vaishampayan

Wash U School of Medicine

Recruiting

St Louis, Missouri, United States, 63110

Contacts

Collin Welch

c.welch@wustl.edu

Principal Investigator:

Jeff Michalski

Nebraska Cancer Specialists

Recruiting

Omaha, Nebraska, United States, 68154

Contacts

Marlene Bridwell

mbridwell@nebraskacancer.com

Principal Investigator:

Samuel Mehr

Astera Cancer Center

Recruiting

East Brunswick, New Jersey, United States, 08816

Contacts

Allison Cabinian

allison.cabinian@asterahealthcare.org

Principal Investigator:

Phillip D Reid

New Jersey Urology LLC

Recruiting

Voorhees Township, New Jersey, United States, 08043

Contacts

Gabriela Mercado

856-673-1613 gmercado3@nj-urology.com

Principal Investigator:

Gordon Brown

New Mexico Oncology Hematology

Recruiting

Albuquerque, New Mexico, United States, 87109

Contacts

Kimberly Demos

+1 505 822 3869#3867 kimberlyd@nmohc.com

Principal Investigator:

Gregg Franklin

Bassett Medical Center

Recruiting

Cooperstown, New York, United States, 13326

Contacts

Peggy Cross

peggy.cross@bassett.org

Principal Investigator:

Timothy Korytko

Weill Cornell Medicine NY-Presb

Recruiting

New York, New York, United States, 10021

Contacts

Sarah Yuan

646-962-2535 say7008@med.cornell.edu

Principal Investigator:

Scott Tagawa

University of Rochester Medical Ctr

Recruiting

Rochester, New York, United States, 14642

Contacts

Therese Smudzin

Therese_Smudzin@urmc.rochester.edu

Principal Investigator:

Haoming Carl Qiu

Associated Med Professionals of NY

Recruiting

Syracuse, New York, United States, 13210

Contacts

Nathan Forrest

nathan.forrest@ampofny.com

Principal Investigator:

Steven Finkelstein

Montefiore Medical Center

Recruiting

The Bronx, New York, United States, 10461

Contacts

Tahrima Chowdhury

718-920-2680 tahchowdhu@montefiore.org

Principal Investigator:

Benjamin A Gartrell

Urology Group - Solaris Network

Recruiting

Cincinnati, Ohio, United States, 45212

Contacts

William Corbett

wcorbett@urologygroup.com

Principal Investigator:

Marc Pliskin

Central Ohio Urology Group

Recruiting

Gahanna, Ohio, United States, 43230

Contacts

Sam Carey

Sam.Carey@centralohiourology.com

Principal Investigator:

Benjamin Martin

MUSC Hollings Cancer Center

Recruiting

Charleston, South Carolina, United States, 29425

Contacts

Alex Jones

joalex@musc.edu

Principal Investigator:

Kevin Becker

Carolina Urologic Research Center

Recruiting

Myrtle Beach, South Carolina, United States, 29572

Contacts

Rebecca Floyd

843-839-1679 rebecca.floyd@startresearch.com

Principal Investigator:

Neal D Shore

Tennessee Oncology PLLC

Recruiting

Chattanooga, Tennessee, United States, 37404

Contacts

Mercedes Bruce

mbruce@tnonc.com

Principal Investigator:

Katy Beckermann

Urology Austin

Recruiting

Lakeway, Texas, United States, 78738

Contacts

Christine Chau

christine.chau@urologyaustin.com

Principal Investigator:

Brian Mazzarella

Urology San Antonio

Recruiting

San Antonio, Texas, United States, 78229

Contacts

Sandra Davila

sandra.davila@usa-clinicaltrials.com

Principal Investigator:

Daniel Saltzstein

Woodlands Cancer Institute American Oncology Partners

Recruiting

The Woodlands, Texas, United States, 77384

Contacts

Brittany Rogers

brittany.rogers@aoncology.com

Principal Investigator:

Jason Berilgen

Swedish Medical Center

Recruiting

Seattle, Washington, United States, 98122-4379

Contacts

Brianna McNealley

855-922-6237 brianna.mcnealley@swedish.org

Principal Investigator:

Song Zhao

Northwest Medical Specialties

Recruiting

Tacoma, Washington, United States, 98405

Contacts

Patricia Walsh

pwalsh@nwmsonline.com

Principal Investigator:

Li Zhang

Medical College of Wisconsin

Recruiting

Milwaukee, Wisconsin, United States, 53226

Contacts

Mariah Ziegler

414-805-5249 mziegler@mcw.edu

Principal Investigator:

Deepak Kilari

More Information

Sponsor

Novartis Pharmaceuticals

Last update posted

Aug 27, 2026

Last verified

Aug, 2026

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

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-08. This information was provided to ClinicalTrials.gov by Novartis Pharmaceuticals on 2026-08-27.