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

NCT ID: NCT05983198

Last Updated: 2025-12-22

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

ACTIVE_NOT_RECRUITING

Clinical Phase

PHASE1/PHASE2

Total Enrollment

29 participants

Study Classification

INTERVENTIONAL

Study Start Date

2023-11-07

Study Completion Date

2029-11-05

Brief Summary

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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.

Enrollment of all participants was not completed. The evaluated radioligand showed acceptable safety but limited benefit in metastatic prostate cancer

Detailed Description

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The study contains three groups (Group 1, Group 2, and Group 3). Each group has a dose escalation part at a specific dosing schedule followed by a dose expansion part. The dose escalation parts in each group within each dosing schedule will establish the maximum tolerated dose or the recommended dose for expansion (MTDs/RDEs) of the 225Ac-PSMA-R2. Dose escalation decisions will be made by the Investigators and Novartis during dose escalation meetings (DEMs) based on safety and tolerability information. The dose expansion parts in each group group/dosing schedule will assess the anti-tumor activity in the mHSPC and mCRPC populations.

Conditions

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Prostate Cancer

Keywords

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225Ac-PSMA-R2 dose limiting toxicity DLT Escalation with Overdose Control EWOC pre- and post-177Lu-PSMA-RLT

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

SEQUENTIAL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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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.

Group Type EXPERIMENTAL

225Ac-PSMA-R2

Intervention Type DRUG

PSMA-R2 is a ligand coupled with 225Ac an alpha emitting radionuclide

68Ga-PSMA-R2

Intervention Type RADIATION

Kit for radiopharmaceutical preparation

68Ga-PSMA-11

Intervention Type RADIATION

Kit for radiopharmaceutical preparation

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.

Group Type EXPERIMENTAL

225Ac-PSMA-R2

Intervention Type DRUG

PSMA-R2 is a ligand coupled with 225Ac an alpha emitting radionuclide

68Ga-PSMA-R2

Intervention Type RADIATION

Kit for radiopharmaceutical preparation

68Ga-PSMA-11

Intervention Type RADIATION

Kit for radiopharmaceutical preparation

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.

Group Type EXPERIMENTAL

225Ac-PSMA-R2

Intervention Type DRUG

PSMA-R2 is a ligand coupled with 225Ac an alpha emitting radionuclide

68Ga-PSMA-R2

Intervention Type RADIATION

Kit for radiopharmaceutical preparation

68Ga-PSMA-11

Intervention Type RADIATION

Kit for radiopharmaceutical preparation

Interventions

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225Ac-PSMA-R2

PSMA-R2 is a ligand coupled with 225Ac an alpha emitting radionuclide

Intervention Type DRUG

68Ga-PSMA-R2

Kit for radiopharmaceutical preparation

Intervention Type RADIATION

68Ga-PSMA-11

Kit for radiopharmaceutical preparation

Intervention Type RADIATION

Other Intervention Names

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Locametz

Eligibility Criteria

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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).

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
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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BAMF Health

Grand Rapids, Michigan, United States

Site Status

Mayo Clinic Rochester

Rochester, Minnesota, United States

Site Status

Novartis Investigative Site

Darlinghurst, New South Wales, Australia

Site Status

Novartis Investigative Site

Melbourne, Victoria, Australia

Site Status

Novartis Investigative Site

Montreal, Quebec, Canada

Site Status

Novartis Investigative Site

Montreal, Quebec, Canada

Site Status

Novartis Investigative Site

Dijon, Cote D Or, France

Site Status

Novartis Investigative Site

Clermont-Ferrand, , France

Site Status

Novartis Investigative Site

Lyon, , France

Site Status

Novartis Investigative Site

Nantes, , France

Site Status

Novartis Investigative Site

Saint-Herblain, , France

Site Status

Novartis Investigative Site

Vandœuvre-lès-Nancy, , France

Site Status

Countries

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United States Australia Canada France

Other Identifiers

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2021-003478-30

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

CAAA802A12101

Identifier Type: -

Identifier Source: org_study_id