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

Clinicaltrials.gov ID: NCT05983198

Status RECRUITING

Phase PHASE1, PHASE2

Age 18 - 100 Years

Enrollments 70

Conditions

Prostate Cancer

Drugs

225Ac-PSMA-R2

Summary

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.

Detailed 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.

Locations

1 location Found with status Recruiting

Status

RECRUITING

Contact Person

Tracey Clasemann
507-538-2155
[email protected]

Study Director

Novartis Pharmaceuticals

Eligibility 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.

Study Plan

Group-1 (mCRPC/ post-177Lu)

EXPERIMENTAL

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.n2. 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
Description:
PSMA-R2 is a ligand coupled with 225Ac an alpha emitting radionuclide
RADIATION:
68Ga-PSMA-R2
Description:
Kit for radiopharmaceutical preparation
RADIATION:
68Ga-PSMA-11
Description:
Kit for radiopharmaceutical preparation

Group-2 (mCRPC/ pre-177Lu)

EXPERIMENTAL

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 nau00efve) 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.n2. Dose Expansion: Once RDE is determined for Group 2, participants nau00efve to 177Lu-labelled PSMA-targeted Radioligand Therapy (RLT) will be enrolled in Group 2 dose expansion.

DRUG:
225Ac-PSMA-R2
Description:
PSMA-R2 is a ligand coupled with 225Ac an alpha emitting radionuclide
RADIATION:
68Ga-PSMA-R2
Description:
Kit for radiopharmaceutical preparation
RADIATION:
68Ga-PSMA-11
Description:
Kit for radiopharmaceutical preparation

Group 3 (mHSPC/ pre-177Lu)

EXPERIMENTAL

1. Dose Escalation: All eligible participants with mHSPC (177Lu-labelled PSMA-targeted RLT treatment nau00efve), 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.n2. Dose Expansion: Once RDE is determined for Group 3, participants will be enrolled in Group 3 dose expansion.

DRUG:
225Ac-PSMA-R2
Description:
PSMA-R2 is a ligand coupled with 225Ac an alpha emitting radionuclide
RADIATION:
68Ga-PSMA-R2
Description:
Kit for radiopharmaceutical preparation
RADIATION:
68Ga-PSMA-11
Description:
Kit for radiopharmaceutical preparation

Outcome Measures

Primary Outcome Measures

Incidence and severity of DLTs during the DLT observation period

Time Frame: 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

Dose Escalation: Tolerability

Time Frame: 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