Phase I/II Study of [225Ac]Ac-PSMA-R2 in PSMA-positive Prostate Cancer, With/Without Prior 177Lu-PSMA RLT (SatisfACtion)

April 23, 2026 updated by: Novartis Pharmaceuticals

SatisfACtion: Phase I/II, Open-label, Multi-center Study of [225Ac]Ac-PSMA-R2 in Men With mHSPC and Heavily Pre-treated PSMA-positive mCRPC, With/Without Prior 177Lu-labelled PSMA-targeted Radioligand Therapy

This is an open label, phase I/II, multi-center study in adult participants with metastatic hormone sensitive prostate cancer (mHSPC) and with metastatic castration resistant prostate cancer (mCRPC) who have received prior anti-cancer treatment and have a positive 68Ga-PSMA-11 PET scan. The purpose of this study is to learn if the study drug, [225Ac]Ac-PSMA-R2, is safe and tolerable, and has anti-tumor activity in treated patients.

Study Overview

Status

Active, not recruiting

Conditions

Intervention / Treatment

Detailed Description

The study contains three groups (Group 1, Group 2, and Group 3). Enrollment and dosing have concluded for study participants. Further study enrollment has been halted for non-safety reasons.

Study Type

Interventional

Enrollment (Actual)

33

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

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

Study Locations

  • Australia
    • New South Wales
      • Darlinghurst, New South Wales, Australia, 2010
        • Novartis Investigative Site
  • Canada
    • Quebec
      • Montreal, Quebec, Canada, H3T 1E2
        • Novartis Investigative Site
      • Montreal, Quebec, Canada, H2X 1R9
        • Novartis Investigative Site
  • France
      • Clermont-Ferrand, France, 63011
        • Novartis Investigative Site
      • Lyon, France, 69373
        • Novartis Investigative Site
      • Nantes, France, 44093
        • Novartis Investigative Site
      • Saint-Herblain, France, 44805
        • Novartis Investigative Site
      • Vandœuvre-lès-Nancy, France, 54511
        • Novartis Investigative Site
    • Cote D Or
      • Dijon, Cote D Or, France, 21034
        • Novartis Investigative Site
  • United States
    • Michigan
      • Grand Rapids, Michigan, United States, 49503
        • BAMF Health
    • Minnesota
      • Rochester, Minnesota, United States, 55905
        • Mayo Clinic Rochester

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

Key Inclusion Criteria:

  • Evidence of PSMA-positive disease by 68Ga-PSMA-11 PET/CT and eligible as determined by central reading
  • Documented progressive mCRPC or mHSPC
  • Adequate organ function
  • Prior orchiectomy or ongoing ADT and should have received prior 177Lu-PSMA-RLT (Group1 dose escalation & expansion) or never received 177Lu-PSMA-RLT (Group 2 and Group 3 dose escalation & expansion).

Key Exclusion Criteria:

  • Any other investigational agents within 28 days of the anticipated C1D1 of 225Ac-PSMA-R2 therapy
  • Any systemic anti-cancer therapy within 28 days of the anticipated C1D1 of 225Ac-PSMA-R2 therapy
  • Uncontrolled pain or incompatibility that may result in participant's lack of ability to comply with imaging procedures
  • History of CNS metastases and symptomatic cord compression, or clinical or radiologic findings indicative of impending cord compression
  • History of myocardial infarction, angina pectoris, or coronary artery bypass graft within 6 months prior to ICF signature and/or clinically active significant cardiac disease
  • Diagnosis of other malignancies in the past three years expected to alter life expectancy or may interfere with disease assessment

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: Non-Randomized
  • Interventional Model: Sequential Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Group-1 (mCRPC/ post-177Lu)
  1. Dose Escalation: All eligible participants with Metastatic Castration Resistant Prostate Cancer (mCRPC) who have received anti-cancer treatment (post-Androgen Receptor Pathway Inhibitors (ARPI), post-taxane based chemotherapy and heavily pre-treated and having already received prior 177Lu-labelled Prostate Specific Membrane Antigen (PSMA)-targeting Radioligand Therapy (RLT) will receive the starting dose of 7 Megabecquerel (MBq) of 225Ac-PSMA-R2 to determine the Maximum Tolerated Dose/Recommended Dose for Expansion (MTD/RDE) of Group 1.
  2. Dose Expansion: Once RDE is determined for Group 1, participants who have previously received 177Lu-PSMA-RLT will be enrolled in Group 1 dose expansion.
Drug: 225Ac-PSMA-R2
PSMA-R2 is a ligand coupled with 225Ac an alpha emitting radionuclide
Radiation: 68Ga-PSMA-R2
Kit for radiopharmaceutical preparation
Radiation: 68Ga-PSMA-11
Kit for radiopharmaceutical preparation
Other Names:
  • Locametz
Experimental: Group-2 (mCRPC/ pre-177Lu)
  1. Dose Escalation: All eligible participants with mCRPC who have received anti-cancer treatment (post-Androgen Receptor Pathway Inhibitors (ARPI), prior taxane-based chemotherapy is not required, but have never been treated with 177Lu-labelled PSMA-targeted RLT (177Lu-labelled PSMA-targeted RLT treatment naïve) will receive the starting dose of 7 Megabecquerel (MBq) of 225Ac-PSMA-R2 to determine the Maximum Tolerated Dose/Recommended Dose for Expansion (MTD/RDE) of Group 2.
  2. Dose Expansion: Once RDE is determined for Group 2, participants naïve to 177Lu-labelled PSMA-targeted Radioligand Therapy (RLT) will be enrolled in Group 2 dose expansion.
Drug: 225Ac-PSMA-R2
PSMA-R2 is a ligand coupled with 225Ac an alpha emitting radionuclide
Radiation: 68Ga-PSMA-R2
Kit for radiopharmaceutical preparation
Radiation: 68Ga-PSMA-11
Kit for radiopharmaceutical preparation
Other Names:
  • Locametz
Experimental: Group 3 (mHSPC/ pre-177Lu)
  1. Dose Escalation: All eligible participants with mHSPC (177Lu-labelled PSMA-targeted RLT treatment naïve), who are treatment naive or minimally treated with a) luteinizing hormone-releasing hormone (LHRH) agonist/antagonists or bilateral orchiectomy with or without first generation antiandrogen (e.g. bicalutamide, flutamide) b) CYP17 inhibitor or ARDT exposure. Patient in this group will start treatment with 225Ac-PSMA-R2 after group 1 and group 2 patients.
  2. Dose Expansion: Once RDE is determined for Group 3, participants will be enrolled in Group 3 dose expansion.
Drug: 225Ac-PSMA-R2
PSMA-R2 is a ligand coupled with 225Ac an alpha emitting radionuclide
Radiation: 68Ga-PSMA-R2
Kit for radiopharmaceutical preparation
Radiation: 68Ga-PSMA-11
Kit for radiopharmaceutical preparation
Other Names:
  • Locametz

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Dose Escalation: Tolerability
Time Frame: Up to 6 weeks after the first 225AC-PSMA-R2 dose administration
Frequency of dose interruptions, reductions, discontinuations, and dose intensity by group.
Up to 6 weeks after the first 225AC-PSMA-R2 dose administration
Dose Expansion: Overall Response Rate (ORR)
Time Frame: From date of the first administration of 225Ac-PSMA-R2 until date of radiographic progression or date of death from any cause, whichever comes first, assessed up to approximately 15 months
Overall Response Rate (ORR) is defined as the proportion of participants with confirmed best overall response (BOR) of complete response (CR) or partial response (PR) in soft tissue according to Prostate Cancer Working Group 3 (PCWG3) -modified RECIST v1.1 in absence of bone progression (as per PCWG3).
From date of the first administration of 225Ac-PSMA-R2 until date of radiographic progression or date of death from any cause, whichever comes first, assessed up to approximately 15 months
Incidence and severity of DLTs during the DLT observation period
Time Frame: Up to 6 weeks after the first 225Ac-PSMA-R2 dose administration

To determine the Recommended Dose for Expansion (RDE) and corresponding regimen for 225Ac-PSMA-R2 monotherapy in PSMA-positive in:

  • Group-1 (mCRPC): Participants previously treated with 177Lu-labelled PSMA-targeted RLT (post-177Lu).
  • Group-2 (mCRPC): Participants not treated previously with 177Lu-labelled PSMA-targeted RLT (pre-177Lu).
  • Group-3 (mHSPC): Participants not treated previously with 177Lu-labelled PSMA-targeted RLT (pre-177Lu).
Up to 6 weeks after the first 225Ac-PSMA-R2 dose administration
Dose Escalation: Incidence and severity of adverse events (AEs) and serious adverse events (SAEs) by group and frequency schedule
Time Frame: From date of the first administration of 225Ac-PSMA-R2 till 30 days safety follow-up, assessed up to approximately 15 months
The distribution of adverse events will be done via the analysis of frequencies for treatment emergent Adverse Event (TEAEs), Serious Adverse Event (TESAEs) and Deaths due to AEs, through the monitoring of relevant clinical and laboratory safety parameters.
From date of the first administration of 225Ac-PSMA-R2 till 30 days safety follow-up, assessed up to approximately 15 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Dose Escalation: Incidence and severity of AEs and serious adverse events (SAEs)
Time Frame: Up to 6 months after the last 225Ac-PSMA-R2 dose administration
Analysis of frequencies for treatment emergent Adverse Event (TEAEs), Serious Adverse Event (TESAEs) and Deaths due to AEs, through the monitoring of relevant clinical and laboratory safety parameters.
Up to 6 months after the last 225Ac-PSMA-R2 dose administration
Dose Expansion: Incidence and severity of AEs and serious adverse events (SAEs)
Time Frame: Assessed up to approximately 15 months.
Analysis of frequencies for treatment emergent Adverse Event (TEAEs), Serious Adverse Event (TESAEs) and Deaths due to AEs, through the monitoring of relevant clinical and laboratory safety parameters.
Assessed up to approximately 15 months.
Dose Escalation & Dose Expansion: Frequency of dose interruptions, reductions, discontinuations, and dose intensity by treatment.
Time Frame: At day 1 of each cycle (1 cycle = up to 6 weeks)
Tolerability of study drug will be assessed by summarizing the number of and the reasons for dose delays and dose reductions. Dose intensity will also be tabulated by treatment group.
At day 1 of each cycle (1 cycle = up to 6 weeks)
Dose Escalation: Overall Response Rate (ORR)
Time Frame: Assessed up to approximately 15 months.
Overall Response Rate (ORR) is defined as the proportion of participants with best overall response (BOR) of complete response (CR) or partial response (PR) in soft tissue.
Assessed up to approximately 15 months.
Dose Escalation & Dose Expansion: Disease Control Rate (DCR)
Time Frame: Assessed up to approximately 15 months.
Disease control rate (DCR) is defined as the proportion of participants with confirmed best overall response (BOR) of complete response (CR), partial response (PR) or stable disease (SD).
Assessed up to approximately 15 months.
Dose Escalation & Dose Expansion: Best Overall Response (BOR)
Time Frame: Assessed up to approximately 15 months.
Best Overall Response (BOR) is defined as the best response recorded from the start of the treatment until disease progression.
Assessed up to approximately 15 months.
Dose Escalation & Dose Expansion: radiographic Progression Free Survival (rPFS)
Time Frame: Assessed up to approximately 15 months.
Radiographic progression free survival (rPFS) is defined as the time (in months) from the date of the first administration of 225Ac-PSMA-R2 to the date of radiographic progression as outlined in PCWG3 modified RECIST 1.1 or death due to any cause.
Assessed up to approximately 15 months.
Dose Escalation & Dose Expansion: Overall Survival (OS)
Time Frame: Assessed up to approximately 15 months.
Overall survival (OS) is defined as the time (in months) from the date of the first administration of 225Ac-PSMA-R2 to the date of death due to any cause.
Assessed up to approximately 15 months.
Dose Escalation & Dose Expansion: Duration of Response (DoR)
Time Frame: Assessed up to approximately 15 months.
Duration of response (DOR) is defined as the time (in months) from the date of the first documented response (CR or PR) to the date of first documented progression.
Assessed up to approximately 15 months.
Dose Escalation & Dose Expansion: Time to first Symptomatic Skeletal Event (SSE)
Time Frame: Assessed up to approximately 15 months.
Time to a first symptomatic skeletal event (SSE) is defined as the time (in months) from the first administration of 225Ac-PSMA-R2 to the date of SSE or death due to any cause.
Assessed up to approximately 15 months.
Dose Escalation & Dose Expansion: Percentage of Participants with Biochemical Response by ALP and LDH
Time Frame: Assessed up to approximately 15 months.
Biochemical responses by Alkaline Phosphatase (ALP) and Lactate Dehydrogenase (LDH) will be measured as best percentage change from baseline
Assessed up to approximately 15 months.
Dose Escalation and Dose Expansion: Percentage of Participants with Biochemical Response by PSA
Time Frame: Assessed up to approximately 15 months.
Biochemical responses as measured by Prostate Specific Antigen (PSA): PSA50 response is defined as the proportion of participants who have achieved ≥50% decrease from baseline at any time.
Assessed up to approximately 15 months.
Dose Escalation and Dose Expansion: Pharmacokinetics characterization of 225Ac-PSMA-R2
Time Frame: At Cycle (C) 1 Day (D) 1 at different measurement times, and one timepoint at C1 D2, C1 D3 and C1 D4
Venous whole blood samples will be collected for activity-based pharmacokinetics characterization.
At Cycle (C) 1 Day (D) 1 at different measurement times, and one timepoint at C1 D2, C1 D3 and C1 D4
Dose escalation and dose expansion: To assess the impact of 225Ac-PSMA-R2 on participant reported outcomes
Time Frame: From baseline until 24 months after the end of treatment
Change in heath related quality of life.
From baseline until 24 months after the end of treatment

Collaborators and Investigators

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

Sponsor

Novartis Pharmaceuticals

Investigators

  • Study Director: Novartis Pharmaceuticals, 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)

November 7, 2023

Primary Completion (Estimated)

November 19, 2026

Study Completion (Estimated)

November 5, 2029

Study Registration Dates

First Submitted

July 24, 2023

First Submitted That Met QC Criteria

August 8, 2023

First Posted (Actual)

August 9, 2023

Study Record Updates

Last Update Posted (Actual)

April 29, 2026

Last Update Submitted That Met QC Criteria

April 23, 2026

Last Verified

April 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CAAA802A12101
  • 2021-003478-30 (EudraCT Number)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

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.

Clinical Trials on Prostate Cancer

Clinical Trials on 225Ac-PSMA-R2

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Croatia

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

Subscribe