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

Novartis

Status and phase: Active, not recruiting; Phase 2; Phase 1

Conditions: Prostate Cancer

Treatments: Radiation: 68Ga-PSMA-R2; Radiation: 68Ga-PSMA-11; Drug: 225Ac-PSMA-R2

Study type: Interventional

Funder types: Industry

Identifiers

NCT05983198

CAAA802A12101

2021-003478-30 (EudraCT Number)

Details and patient eligibility

About

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

Full description

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.

Enrollment: 29 patients

Sex: Male

Ages: 18 to 100 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

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.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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29 participants in 3 patient groups

Group-1 (mCRPC/ post-177Lu)

Experimental group

Description:

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.

Treatment:

Drug: 225Ac-PSMA-R2

Radiation: 68Ga-PSMA-11

Radiation: 68Ga-PSMA-R2

Group-2 (mCRPC/ pre-177Lu)

Experimental group

Description:

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.

Treatment:

Drug: 225Ac-PSMA-R2

Radiation: 68Ga-PSMA-11

Radiation: 68Ga-PSMA-R2

Group 3 (mHSPC/ pre-177Lu)

Experimental group

Description:

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.

Treatment:

Drug: 225Ac-PSMA-R2

Radiation: 68Ga-PSMA-11

Radiation: 68Ga-PSMA-R2