Open-label Study Comparing AAA817 Versus Standard of Care in the Treatment of Previously Treated PSMA-positive mCRPC Adults Who Have Disease Progressed on or After [177Lu]Lu-PSMA Targeted Therapy (PSMAcTION)

May 25, 2026 updated by: Novartis Pharmaceuticals

PSMAcTION: A Phase II/III, Open-label, International, Multicenter, Randomized Study of AAA817 Versus Standard of Care in the Treatment of Adult Participants With PSMA Positive Metastatic Castration-resistant Prostate Cancer Who Progressed on or After [177Lu]Lu-PSMA Targeted Therapy

This is a Phase II/III study. Patient population is adult participants with PSMA-positive mCRPC who had treatments with androgen receptor pathway inhibitor (ARPI) and taxane-based chemotherapy and progressed on or after [177Lu]Lu-PSMA targeted therapy.

Treatment of interest: the investigational treatment is AAA817 regardless of subsequent anti-neoplastic treatment. The control treatment is investigator's choice of Standard of Care, regardless of subsequent anti-neoplastic treatment

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

Study CAAA817A12201 consists of 2 parts: a randomized, open-label, international, multicenter, phase II study (Phase II) to collect more information to support the proposed dose of AAA817 and a randomized, open-label, international, multicenter, 2- arm phase III study (Phase III) aimed to evaluate the efficacy and safety of proposed dose of AAA817 vs. investigator's choice of standard of care (SoC) in the treatment of adult participants with PSMA-positive metastatic castration-resistant prostate cancer (mCRPC) who had treatments with ARPI and taxane-based chemotherapy, and progressed on or after [177Lu]Lu-PSMA targeted therapy. The purpose of the phase II part (Phase II) of this study is to collect additional information to support proposed phase III dose of AAA817.

Study Type

Interventional

Enrollment (Estimated)

443

Phase

  • Phase 2
  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

  • Name: Novartis Pharmaceuticals
  • Phone Number: +41613241111

Study Locations

  • Australia
    • New South Wales
      • Darlinghurst, New South Wales, Australia, 2010
        • Recruiting
        • Novartis Investigative Site
    • Queensland
      • Herston, Queensland, Australia, 4029
        • Recruiting
        • Novartis Investigative Site
    • Victoria
      • Melbourne, Victoria, Australia, 3004
        • Recruiting
        • Novartis Investigative Site
  • Brazil
    • São Paulo
      • São Paulo, São Paulo, Brazil, 01308-050
        • Recruiting
        • Novartis Investigative Site
      • São Paulo, São Paulo, Brazil, 05652-000
        • Recruiting
        • Novartis Investigative Site
  • China
      • Beijing, China, 100036
        • Recruiting
        • Novartis Investigative Site
      • Beijing, China, 100034
        • Recruiting
        • Novartis Investigative Site
      • Guangzhou, China, 510060
        • Recruiting
        • Novartis Investigative Site
      • Shanghai, China, 200025
        • Recruiting
        • Novartis Investigative Site
      • Shanghai, China, 200032
        • Recruiting
        • Novartis Investigative Site
      • Tianjin, China, 300300
        • Recruiting
        • Novartis Investigative Site
    • Fujian
      • Fuzhou, Fujian, China, 350025
        • Recruiting
        • Novartis Investigative Site
    • Hubei
      • Wuhan, Hubei, China, 430022
        • Recruiting
        • Novartis Investigative Site
      • Wuhan, Hubei, China, 430030
        • Recruiting
        • Novartis Investigative Site
    • Jiangsu
      • Nanjing, Jiangsu, China, 210006
        • Recruiting
        • Novartis Investigative Site
      • Nanjing, Jiangsu, China, 210029
        • Recruiting
        • Novartis Investigative Site
    • Liaoning
      • Shenyang, Liaoning, China, 110011
        • Recruiting
        • Novartis Investigative Site
    • Shanxi
      • Xian, Shanxi, China, 710061
        • Recruiting
        • Novartis Investigative Site
      • Xian, Shanxi, China, 710032
        • Recruiting
        • Novartis Investigative Site
    • Sichuan
      • Chengdu, Sichuan, China, 610041
        • Recruiting
        • Novartis Investigative Site
  • Hong Kong
      • Hong Kong, Hong Kong, 999077
        • Recruiting
        • Novartis Investigative Site
  • Israel
      • Beersheba, Israel, 8457108
        • Recruiting
        • Novartis Investigative Site
      • Haifa, Israel, 3109601
        • Recruiting
        • Novartis Investigative Site
      • Jerusalem, Israel, 9112001
        • Recruiting
        • Novartis Investigative Site
      • Petah Tikva, Israel, 4941492
        • Recruiting
        • Novartis Investigative Site
      • Ramat Gan, Israel, 5265601
        • Recruiting
        • Novartis Investigative Site
      • Tel Aviv, Israel, 6423906
        • Recruiting
        • Novartis Investigative Site
  • Japan
      • Chiba, Japan, 260-8717
        • Recruiting
        • Novartis Investigative Site
      • Fukuoka, Japan, 811-0213
        • Recruiting
        • Novartis Investigative Site
      • Fukuoka, Japan, 812-0033
        • Recruiting
        • Novartis Investigative Site
      • Fukuoka, Japan, 8128582
        • Recruiting
        • Novartis Investigative Site
      • Fukushima, Japan, 9601295
        • Recruiting
        • Novartis Investigative Site
      • Ishikawa, Japan, 9208641
        • Recruiting
        • Novartis Investigative Site
      • Kyoto, Japan, 6068507
        • Recruiting
        • Novartis Investigative Site
    • Chiba
      • Kashiwa, Chiba, Japan, 277-8577
        • Recruiting
        • Novartis Investigative Site
    • Hokkaido
      • Sapporo, Hokkaido, Japan, 060-8648
        • Recruiting
        • Novartis Investigative Site
    • Hyōgo
      • Kobe, Hyōgo, Japan, 6500047
        • Recruiting
        • Novartis Investigative Site
    • Kanagawa
      • Yokohama, Kanagawa, Japan, 236-0004
        • Recruiting
        • Novartis Investigative Site
  • Malaysia
    • Selangor
      • Petaling Jaya, Selangor, Malaysia, 46050
        • Recruiting
        • Novartis Investigative Site
      • Petaling Jaya, Selangor, Malaysia, 46150
        • Recruiting
        • Novartis Investigative Site
  • Singapore
      • Singapore, Singapore, 119228
        • Recruiting
        • Novartis Investigative Site
      • Singapore, Singapore, 168583
        • Recruiting
        • Novartis Investigative Site
      • Singapore, Singapore, 258499
        • Recruiting
        • Novartis Investigative Site
  • South Korea
      • Seoul, South Korea, 03080
        • Recruiting
        • Novartis Investigative Site
      • Seoul, South Korea, 05505
        • Recruiting
        • Novartis Investigative Site
      • Seoul, South Korea, 06591
        • Recruiting
        • Novartis Investigative Site
      • Seoul, South Korea, 03722
        • Recruiting
        • Novartis Investigative Site
  • Switzerland
      • Basel, Switzerland, 4031
        • Recruiting
        • Novartis Investigative Site
      • Bellinzona, Switzerland, 6500
        • Recruiting
        • Novartis Investigative Site
      • Bern, Switzerland, 3010
        • Recruiting
        • Novartis Investigative Site
  • Taiwan
      • Taipei, Taiwan, 10002
        • Recruiting
        • Novartis Investigative Site
      • Taipei, Taiwan, 11217
        • Recruiting
        • Novartis Investigative Site
      • Taipei, Taiwan, 103616
        • Recruiting
        • Novartis Investigative Site
      • Taoyuan, Taiwan, 33305
        • Recruiting
        • Novartis Investigative Site
  • United States
    • California
      • Los Angeles, California, United States, 90073
        • Recruiting
        • VA Greater LA Healthcare System
        • Contact:
        • Principal Investigator:
          • Gholam Reza Berenji
      • Palo Alto, California, United States, 94304-1207
        • Recruiting
        • VA Palo Alto Health Care System
        • Principal Investigator:
          • Minal Vasanawala
        • Contact:
      • Palo Alto, California, United States, 94304
        • Recruiting
        • Stanford University Medical Center
        • Principal Investigator:
          • Hong Song
        • Contact:
      • Santa Barbara, California, United States, 93105
        • Recruiting
        • Sansum Clinic
        • Principal Investigator:
          • Gregg Newman
        • Contact:
      • Santa Monica, California, United States, 90404
        • Recruiting
        • Saint Johns Cancer Institute
        • Principal Investigator:
          • Przemyslaw Twardowski
        • Contact:
    • Connecticut
      • Hartford, Connecticut, United States, 06102
    • Florida
      • Orlando, Florida, United States, 32804
        • Recruiting
        • AdventHealth
        • Principal Investigator:
          • Ravi Shridhar
        • Contact:
    • Georgia
      • Athens, Georgia, United States, 30607
        • Recruiting
        • University Cancer and Blood Center LLC
        • Principal Investigator:
          • PETROS NIKOLINAKOS
        • Contact:
      • Atlanta, Georgia, United States, 30322
        • Recruiting
        • Emory University
        • Contact:
        • Principal Investigator:
          • Shahid Sattar Ahmed.
    • Indiana
      • Indianapolis, Indiana, United States, 46202
        • Recruiting
        • Indiana University
        • Principal Investigator:
          • Nabil Adra
        • Contact:
    • Kansas
      • Kansas City, Kansas, United States, 66160
        • Recruiting
        • University of Kansas Hospital
        • Principal Investigator:
          • Xinglei Shen
        • Contact:
    • Louisiana
      • Metairie, Louisiana, United States, 70006
    • Massachusetts
      • Boston, Massachusetts, United States, 02215
        • Recruiting
        • Beth Israel Deaconess Medical Center
        • Principal Investigator:
          • David J Einstein
        • Contact:
      • Boston, Massachusetts, United States, 02115
        • Recruiting
        • Dana Farber Cancer Institute
        • Contact:
        • Principal Investigator:
          • Xiao Wei.
    • Missouri
      • St Louis, Missouri, United States, 63110
        • Recruiting
        • WA Uni School Of Med
        • Principal Investigator:
          • Jeff Michalski
        • Contact:
    • Nebraska
      • Omaha, Nebraska, United States, 68154
        • Recruiting
        • Nebraska Cancer Specialists
        • Principal Investigator:
          • Samuel Mehr
        • Contact:
    • New Jersey
      • Voorhees Township, New Jersey, United States, 08043
        • Recruiting
        • New Jersey Urology LLC
        • Contact:
        • Principal Investigator:
          • Gordon Brown
    • New York
      • Syracuse, New York, United States, 13210
        • Recruiting
        • Associated Med Professionals of NY
        • Principal Investigator:
          • Steven Finkelstein
        • Contact:
      • The Bronx, New York, United States, 10467
        • Recruiting
        • Montefiore Medical Center
        • Principal Investigator:
          • Benjamin A Gartrell
        • Contact:
    • Ohio
      • Gahanna, Ohio, United States, 43230
        • Recruiting
        • Central Ohio Urology Group
        • Principal Investigator:
          • Benjamin Martin
        • Contact:
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19111
        • Recruiting
        • Fox Chase Cancer Center
        • Contact:
        • Principal Investigator:
          • Matthew Zibelman
    • South Carolina
      • Myrtle Beach, South Carolina, United States, 29572
        • Recruiting
        • Carolina Urologic Research Center
        • Principal Investigator:
          • Neal D Shore
        • Contact:
    • Texas
      • Dallas, Texas, United States, 75251
        • Recruiting
        • Texas Oncology
        • Contact:
        • Principal Investigator:
          • Michael P Herman
      • San Antonio, Texas, United States, 78229
    • Utah
      • Murray, Utah, United States, 84107
        • Recruiting
        • Utah Intermountain Medical Center
        • Principal Investigator:
          • David Gill
        • Contact:
    • Washington
      • Seattle, Washington, United States, 98109-1024
        • Recruiting
        • Fred Hutchinson Cancer Research Center
        • Contact:
        • Principal Investigator:
          • Ruben Raychaudhuri
    • Wisconsin
      • Milwaukee, Wisconsin, United States, 53226
        • Recruiting
        • Medical College of Wisconsin
        • Principal Investigator:
          • Deepak Kilari
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria: ∙

  • adults ≥ 18 years of age.
  • ECOG performance status of 0 to 2.
  • histopathological and/or cytological confirmation of adenocarcinoma of the prostate.
  • PSMA-positive disease as assessed by PSMA PET/CT scan using an approved PSMA imaging agent as protocol instructed,
  • castrate level of serum/plasma testosterone (< 50 ng/dL or < 1.7 nmol/L).
  • Prior treatments with an androgen receptor pathway inhibitor (ARPI) and taxane-based chemotherapy, and progressed on or after [177Lu]Lu-PSMA targeted therapy.
  • ≥ 1 metastatic lesion that is present on screening/baseline CT, MRI, or bone scan imaging obtained ≤ 28 days prior to randomization
  • eGFR as requested by the sponsor

Exclusion Criteria:

  • Any investigational agents within 28 days prior to the day of randomization.
  • Any 225Ac-based investigational compound used prior to the day of randomization.
  • Participants with a history of CNS metastases who are neurologically unstable, symptomatic, or receiving corticosteroids for the purpose of maintaining neurologic integrity.
  • Concurrent acute kidney injury (renal failure developed between 48 hours to 7 days) or chronic kidney disease (at least 3 months of ongoing renal injury)
  • Baseline xerostomia ≥ Grade 2 by CTCAE v.5
  • History of uncontrolled hypertension, myocardial infarction (MI), angina pectoris, or coronary artery bypass graft (CABG) within 6 months prior to ICF signature and/or clinically active significant cardiac disease
  • History of lymphoproliferative disease or any known malignancy or history of malignancy of any organ system within the past 5 years (except for basal cell carcinoma or actinic keratosis that have been treated with no evidence of recurrence in the past 3 months, non-invasive malignant colon polyps that have been removed).

Other protocol-defined inclusion/exclusion criteria may apply.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Phase II: AAA817 Dose B
AAA817 will be given for a number of cycles; a cycle = 8 weeks
Drug: AAA817
The investigational treatment is AAA817
Other Names:
  • [225Ac]Ac-PSMA-617)
Drug: AAA817
Investigational treatment is the Dose B of AAA817
Other Names:
  • [225Ac]Ac-PSMA-617
Active Comparator: Phase III: Investigator's choice of SoC
Participants will be given Standard of Care (SOC) treatment per Investigator's choice.
Drug: Investigators choice of SoC
The control treatment in Phase III is investigator's choice of SoC
Experimental: Phase II: AAA817 Dose A
AAA817 Dose A will be given for a number of cycles: a cycle = 8 weeks
Drug: AAA817
The investigational treatment is AAA817
Other Names:
  • [225Ac]Ac-PSMA-617)
Drug: AAA817
Investigational treatment is the Dose B of AAA817
Other Names:
  • [225Ac]Ac-PSMA-617
Experimental: Phase III: Recommended Phase 3 Dose of AAA817
Rp3D of AAA817 will be given for a number of cycles; a cycle = 8 weeks
Drug: AAA817
The investigational treatment is AAA817
Other Names:
  • [225Ac]Ac-PSMA-617)
Drug: AAA817
Investigational treatment is the Dose B of AAA817
Other Names:
  • [225Ac]Ac-PSMA-617

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Biochemical response rate (Phase II)
Time Frame: from date of randomization up to approximately 24 months
Biochemical response rate as defined as the percentage of participants who achieved a ≥ 50% decrease from baseline that is confirmed by a second measurement
from date of randomization up to approximately 24 months
Adverse Events (AEs) and Serious Adverse Events (SAEs), and deaths - Phase II
Time Frame: from day of randomization to 30 days after End of Treatment or (last AAA817 dose date + 55 days, last dose date of SoC + 30 days), whichever is later
Safety defined as the type, incidence and severity of AEs and SAEs, and deaths
from day of randomization to 30 days after End of Treatment or (last AAA817 dose date + 55 days, last dose date of SoC + 30 days), whichever is later
Tolerability of the proposed dose of AAA817- Phase II
Time Frame: From on-treatment period which start from the first dose of study treatment until 30 days post-last dose date for SoC and 55 days post last-dose for AAA817
Percentage of participants who experienced Dose interruptions, reductions, discontinuation, dose intensity and duration of exposure
From on-treatment period which start from the first dose of study treatment until 30 days post-last dose date for SoC and 55 days post last-dose for AAA817
Radiographic progression-free survival (rPFS)- Phase III
Time Frame: from date of randomization up to approximately 24 months
Percentage of participants who are alive without radiographic progression or who are lost to follow-up at the time of analysis
from date of randomization up to approximately 24 months
Overall survival (OS)- Phase III
Time Frame: from date of randomization up to approximately 24 months
Percentage of participants who are alive or who are lost to follow-up at the time of analysis
from date of randomization up to approximately 24 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Progression free survival (PFS)- Phase II
Time Frame: from date of randomization up to approximately 24 months
Percentage of Participants meeting Progression Free Survival
from date of randomization up to approximately 24 months
Radiographic progression-free survival (rPFS)- Phase II
Time Frame: from date of randomization up to approximately 24 months
Percentage of participants who are alive without radiographic progression or who are lost to follow-up at the time of analysis
from date of randomization up to approximately 24 months
Overall response rate (ORR)- Phase II
Time Frame: from date of randomization up to approximately 24 months
Percentage of participants with best overall response (BOR) of complete response (CR) or partial response (PR)
from date of randomization up to approximately 24 months
Disease control rate (DCR)- Phase II
Time Frame: from date of randomization up to approximately 24 months
Percentage of participants with BOR of CR, PR, stable disease (SD) or non-CR/non-PD
from date of randomization up to approximately 24 months
Overall survival (OS)- Phase II
Time Frame: from date of randomization up to approximately 24 months
Percentage of participants who are alive or who are lost to follow-up at the analysis data cut-off
from date of randomization up to approximately 24 months
Progression free survival (PFS) -Phase III
Time Frame: from date of randomization up to approximately 24 months
Percentage of participants with PFS -defined as the time from date of randomization to first documented progression
from date of randomization up to approximately 24 months
Overall response rate (ORR)- Phase III
Time Frame: from date of randomization up to approximately 24 months
ORR is defined as the percentage of participants with best overall response (BOR) of confirmed complete response (CR) or partial response (PR)
from date of randomization up to approximately 24 months
Disease control rate (DCR) -Phase III
Time Frame: from date of randomization up to approximately 24 months
DCR is defined as the percentage of participants with BOR of confirmed CR, PR, stable disease (SD) or Non-CR/Non progressive disease (PD)
from date of randomization up to approximately 24 months
Duration of response (DoR)- Phase III
Time Frame: from date of randomization up to approximately 24 months
Percentage of participants with confirmed DoR defined as duration of time between the date of first documented response (CR or PR) and progression or death due to any cause, whichever occurs first.
from date of randomization up to approximately 24 months
Time to first radiographic soft tissue progression (TTSTP)- Phase III
Time Frame: from date of randomization up to approximately 24 months
Percentage of participants with confirmed first radiographic progression in soft tissue
from date of randomization up to approximately 24 months
First symptomatic skeletal event (TTSSE)_Phase III
Time Frame: from date of randomization up to approximately 24 months
Percentage of participants with confirmed skeletal event is defined as new symptomatic pathological bone fracture, spinal cord compression, tumor-related orthopedic surgical intervention, or requirement for radiation therapy to relieve bone pain, or death due to any cause, whichever occurs first
from date of randomization up to approximately 24 months
Prostate specific antigen (PSA) response -Phase III
Time Frame: from date of randomization up to approximately 24 months
PSA50 is defined as the percentage of participants who achieved a confirmed ≥ 50% decrease from baseline
from date of randomization up to approximately 24 months
Patient reported disease related symptoms and health-related quality of life (HRQoL): Phase III
Time Frame: from date of randomization up to approximately 24 months
Percentage of participants who had a Change from baseline on FACT-P Prostate Cancer Subscale (PCS)
from date of randomization up to approximately 24 months
Time to worsening on the Worst Pain: Phase III
Time Frame: from date of randomization up to approximately 24 months
Time to worsening on the Worst Pain defined as the time from randomization to the first occurrence of worsening on the Worst Pain item (brief pain inventory - short form (BPI-SF)) of at least 30% of baseline or minimum of 2 points increase from baseline, or death due to any cause, whichever occurs first. BPI-SF is a self-reported questionnaire to evaluate pain intensity (severity) and impact of pain on the participant's daily functioning (interference).
from date of randomization up to approximately 24 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Novartis Pharmaceuticals

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

February 27, 2025

Primary Completion (Estimated)

June 27, 2028

Study Completion (Estimated)

July 19, 2033

Study Registration Dates

First Submitted

December 17, 2024

First Submitted That Met QC Criteria

January 16, 2025

First Posted (Actual)

January 17, 2025

Study Record Updates

Last Update Posted (Actual)

May 27, 2026

Last Update Submitted That Met QC Criteria

May 25, 2026

Last Verified

May 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CAAA817A12201
  • 2024-512342-42-00 (Other Identifier: EU CTIS)

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Subscribe