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NCT Number: NCT05983198

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

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.

Active, Not Recruiting

This study is active but is not currently recruiting participants.

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Key information

Conditions

Prostate Cancer Genital Diseases Genital Diseases, Male Genital Neoplasms, Male Male Urogenital Diseases Neoplasms Neoplasms by Site Prostatic Diseases Prostatic Neoplasms Urogenital Diseases Urogenital Neoplasms

Age range

18 year–100 year

Sex eligibility

Male

Study type

Interventional

Phase

Phase 1

Primary location

Novartis Investigative Site, Darlinghurst, New South Wales, Australia

Loading trial locations.

About this study

First in human (FIH) phase I/II study of 225Ac-PSMA-R2 in PSMA-positive metastatic prostate cancer across three groups: post-177Lu mCRPC, pre-177Lu mCRPC, and 177Lu-naïve mHSPC, evaluating Q6W/Q4W dosing. Dose escalation will enroll ~18-22 participants per group/schedule to define MTD/RDE, guided by safety, tolerability, PK/dosimetry, and preliminary anti-tumor activity, with possible expansion based on benefit-risk.

Enrollment and dosing for all participants in Group 1, Group 2, and Group 3 have been completed. Further enrollment has been halted, and no additional dose escalation cohorts or Phase 2 dose expansion cohorts will be opened; enrollment in this study is now considered complete. The decision to halt enrolment was not driven by any safety concerns identified in the study to date, but rather by a lowered expectation of benefit. Accordingly, the study will not proceed to Phase 2, and a recommended Phase 2 dose was not established

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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.

Treatment and study plan

225Ac-PSMA-R2

Drug

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

68Ga-PSMA-R2

Radiation

Kit for radiopharmaceutical preparation

68Ga-PSMA-11

Radiation

Kit for radiopharmaceutical preparation

Other names: Locametz

Primary outcomes

  1. Phase I Dose Escalation: 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).

  2. Phase I 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.

  3. Phase I 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.

  4. Phase ll 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).

Secondary outcomes

  1. Phase I 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.

  2. Phase ll: 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.

  3. Phase I 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.

  4. Phase I 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.

  5. Phase I Dose Escalation & Phase II 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).

  6. Phase I Dose Escalation & Phase II 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.

  7. Phase I Dose Escalation & Phase II 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.

  8. Phase I Dose Escalation & Phase II 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.

  9. Phase I Dose Escalation & Phase II 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.

  10. Phase I Dose Escalation & Phase II 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.

  11. Phase I Dose Escalation & Phase II 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

  12. Phase I Dose Escalation and Phase II 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.

  13. Phase I Dose Escalation and Phase II: 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.

  14. Phase I Dose Escalation and Phase II 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.

Sponsors and collaborators

Lead sponsor

Novartis Pharmaceuticals

Industry

Registry information

Official study 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

Acronym: SatisfACtion

Important dates

Study start
2023
Primary completion
2031
Study completion
2031
First posted
Aug 9, 2023
Registry last updated
Jun 29, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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