Clinical trial NCT05983198: Phase I/II Study of [225Ac]Ac-PSMA-R2 in PSMA-positive Prostate Cancer, With/Without Prior 177Lu-PSMA RLT
Official title: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: Prostate Cancer
Keywords: 225Ac-PSMA-R2
dose limiting toxicity
DLT
Escalation with Overdose Control
EWOC
pre- and post-177Lu-PSMA-RLT
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2023-08-09
Enrollment: 70
Sex: MALE
Minimum age (years): 18
Maximum age (years): 100
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief 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.

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.

Primary outcomes:
measure: Incidence and severity of DLTs during the DLT observation period
timeFrame: Up to 6 weeks after the first 225Ac-PSMA-R2 dose administration
measure: Dose Escalation: Incidence and severity of adverse events (AEs) and serious adverse events (SAEs) by group and frequency schedule
timeFrame: From date of the first administration of 225Ac-PSMA-R2 till 30 days safety follow-up, assessed up to approximately 15 months
measure: Dose Escalation: Tolerability
timeFrame: Up to 6 weeks after the first 225AC-PSMA-R2 dose administration
measure: Dose Expansion: Overall Response Rate (ORR)
timeFrame: 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
Secondary outcomes:
measure: Dose Escalation: Incidence and severity of AEs and serious adverse events (SAEs)
timeFrame: Up to 6 months after the last 225Ac-PSMA-R2 dose administration
measure: Dose Expansion: Incidence and severity of AEs and serious adverse events (SAEs)
timeFrame: Assessed up to approximately 15 months.
measure: Dose Escalation & Dose Expansion: Frequency of dose interruptions, reductions, discontinuations, and dose intensity by treatment.
timeFrame: At day 1 of each cycle (1 cycle = up to 6 weeks)
measure: Dose Escalation: Overall Response Rate (ORR)
timeFrame: Assessed up to approximately 15 months.
measure: Dose Escalation & Dose Expansion: Disease Control Rate (DCR)
timeFrame: Assessed up to approximately 15 months.
measure: Dose Escalation & Dose Expansion: Best Overall Response (BOR)
timeFrame: Assessed up to approximately 15 months.
measure: Dose Escalation & Dose Expansion: radiographic Progression Free Survival (rPFS)
timeFrame: Assessed up to approximately 15 months.
measure: Dose Escalation & Dose Expansion: Overall Survival (OS)
timeFrame: Assessed up to approximately 15 months.
measure: Dose Escalation & Dose Expansion: Duration of Response (DoR)
timeFrame: Assessed up to approximately 15 months.
measure: Dose Escalation & Dose Expansion: Time to first Symptomatic Skeletal Event (SSE)
timeFrame: Assessed up to approximately 15 months.
measure: Dose Escalation & Dose Expansion: Percentage of Participants with Biochemical Response by ALP and LDH
timeFrame: Assessed up to approximately 15 months.
measure: Dose Escalation and Dose Expansion: Percentage of Participants with Biochemical Response by PSA
timeFrame: Assessed up to approximately 15 months.
measure: Dose Escalation and Dose Expansion: Pharmacokinetics characterization of 225Ac-PSMA-R2
timeFrame: At Cycle (C) 1 Day (D) 1 at different measurement times, and one timepoint at C1 D2, C1 D3 and C1 D4
measure: Dose escalation and dose expansion: To assess the impact of 225Ac-PSMA-R2 on participant reported outcomes
timeFrame: From baseline until 24 months after the end of treatment
Other outcomes:
Locations:
city: Darlinghurst
country: Australia
facility: Novartis Investigative Site
state: New South Wales
city: Montreal
country: Canada
facility: Novartis Investigative Site
state: Quebec
city: Montreal
country: Canada
facility: Novartis Investigative Site
state: Quebec
city: Dijon
country: France
facility: Novartis Investigative Site
state: Cote D Or
city: Clermont-Ferrand
country: France
facility: Novartis Investigative Site
city: Lyon
country: France
facility: Novartis Investigative Site
city: Nantes Cedex 1
country: France
facility: Novartis Investigative Site
city: Saint Herblain
country: France
facility: Novartis Investigative Site
city: Vandoeuvre Les Nancy
country: France
facility: Novartis Investigative Site
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References: