Study of 225Ac-PSMA-617 in Men With PSMA-positive Prostate Cancer

NCT04597411 | Active Not Recruiting Phase 1

• 2 other identifiers: PSMA-617-100CAAA817A12101
• Study Type: interventional
• Target: 101
• Locations: 2 countries
• Sites: 2

Brief Summary

This is a Phase 1, open-label, international, dose escalation study to evaluate the safety of \[225Ac\]Ac-PSMA-617 (225Ac-PSMA-617) in men with PSMA-positive prostate cancer who have and have not had prior exposure to \[177Lu\]Lu-PSMA-617 (177Lu-PSMA-617) or \[177Lu\]Lu-PSMA I\&T (177Lu-PSMA I\&T).

Conditions

Prostatic Neoplasms, Castration-Resistant

Keywords

Androgen-Resistant Prostatic Neoplasms; Castration-Resistant Prostatic Cancer; Castration-Resistant Prostatic Neoplasms; Prostatic Cancer, Castration-Resistant; Prostatic Neoplasms; Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Prostatic Diseases; [225Ac]Ac-PSMA-617; 225Ac-PSMA-617; [68Ga]Ga-PSMA-11; 68Ga-PSMA-11; [177Lu]Lu-PSMA-617; 177Lu-PSMA-617; [177Lu]Lu-PSMA I&T; 177Lu-PSMA I&T

Outcome Measures

Primary Outcomes (1)

• Recommended Phase 2 Dose (RP2D)

  The RP2D for each group (Group A, B and C) is defined as the dose level that is well tolerated (i.e., at or below the MTD) and for which there may be additional findings (e.g., longer term tolerability) effecting the RP2D decision. In the case where an MTD is not identified, even at the highest dose level tested, the RP2D may be determined on the basis of data indicating adequate tolerability and therapeutic effectiveness.

  6 weeks post Cycle 1 Day 1 (C1D1) of each dosing cohort through enrollment completion, an average of 1.5 years to determine RP2D

Secondary Outcomes (13)

• Percentage of Participants with treatment emergent adverse events

  Day 1/Infusion Day up to 60 days post infusion

• Overall Response Rate (ORR)

  Every 8 weeks after first dose of 225Ac-PSMA-617 for the first 24 weeks, then every 12 weeks through the end of treatment visit, on average 2.5 years

• Duration of Response (DOR)

  Every 8 weeks after first dose of 225Ac-PSMA-617 for the first 24 weeks, then every 12 weeks through the end of treatment visit, on average 2.5 years

• Disease Control Rate (DCR)

  Every 8 weeks after first dose of 225Ac-PSMA-617 for the first 24 weeks, then every 12 weeks through the end of treatment visit, on average 2.5 years

• Progression Free Survival (PFS)

  Every 8 weeks after first dose of 225Ac-PSMA-617 for the first 24 weeks, then every 12 weeks through the end of treatment visit, on average 2.5 years

Study Arms (3)

Group A (mCRPC who have received prior ARPI and chemotherapy, but are PSMA RLT naïve)

EXPERIMENTAL

Men that have received prior cytotoxic chemotherapy and ARPI (e.g., abiraterone or enzalutamide), who HAVE NOT been previously treated with 177Lu-PSMA-617 radioligand therapy or 177Lu-PSMA I\&T will receive a dose of 225\^Ac-PSMA-617 via intravenous injection every 8 weeks (+/- 1 week) for a maximum of 6 cycles.

Radiation: 225^Ac-PSMA-617; Radiation: 68^Ga-PSMA-11

Group B (mCRPC who have not had prior ARPI or chemotherapy, and are PSMA RLT naïve)

EXPERIMENTAL

Men previously treated with luteinizing hormone-releasing hormone (LHRH) agonists or orchiectomy and primary anti-androgen therapy that have not received prior cytotoxic chemotherapy or novel androgen axis drugs (e.g., abiraterone or enzalutamide) will receive a dose of 225Ac-PSMA-617 via intravenous injection every 8 weeks (+/- 1 week) for a maximum of 6 cycles.

Radiation: 225^Ac-PSMA-617; Radiation: 68^Ga-PSMA-11

Group C (mCRPC who have received prior PSMA RLT)

EXPERIMENTAL

Men with progressive metastatic castration resistant prostate cancer (mCRPC) who HAVE been previously treated with 177Lu-PSMA-617 radioligand therapy or 177Lu-PSMA I\&T will receive a dose of 225Ac-PSMA-617 via intravenous injection every 8 weeks (+/- 1 week) for a maximum of 6 cycles. Prior chemotherapy and/or novel androgen axis drugs not required.

Radiation: 225^Ac-PSMA-617; Radiation: 68^Ga-PSMA-11

Interventions

225^Ac-PSMA-617 RADIATION

administered intravenously under the dose escalation schedule

Group A (mCRPC who have received prior ARPI and chemotherapy, but are PSMA RLT naïve); Group B (mCRPC who have not had prior ARPI or chemotherapy, and are PSMA RLT naïve); Group C (mCRPC who have received prior PSMA RLT)

68^Ga-PSMA-11 RADIATION

administered intravenously at a dose of 111 - 185 MBq (3 - 5 mCi)

Group A (mCRPC who have received prior ARPI and chemotherapy, but are PSMA RLT naïve); Group B (mCRPC who have not had prior ARPI or chemotherapy, and are PSMA RLT naïve); Group C (mCRPC who have received prior PSMA RLT)

Eligibility Criteria

• Age: 18 Years+
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients must have the ability to understand and sign an approved ICF.
• Patients must have the ability to understand and comply with all protocol requirements.
• Patients must be \>=18 years of age.
• Patients must have an ECOG performance status of 0 to 2.
• Patients must have had histological, pathological, and/or cytological confirmation of prostate cancer.
• Patients must have a positive 68Ga-PSMA-11 PET/CT scan performed within 28 days of study entry. If a patient also has soft tissue or visceral disease, it must be PSMA-positive on 68Ga-PSMA-11 PET/CT scan.
• Patients may not participate in the study if their baseline scan shows PSMA-negative disease (defined as disease that expresses PSMA at a level equal to or less than liver by visual assessment) in any of the following regions:
• A) One or more PSMA negative lymph nodes \>2.5 cm on short axis B) Bone metastasis with PSMA-negative soft tissues component \> 1 cm in short axis
• Note that PSMA-negative osseous metastases without a soft tissue component \>1 cm does not exclude the subject C) PSMA-negative solid organ metastases (i.e. lung, liver, adrenal glands, etc) that are PSMA-negative and ≥ 1cm in short axis
• Patients must have recovered or stabilized to =\< Grade 2 or baseline from all clinically significant toxicities related to prior prostate cancer therapy.
• Determination of disease progression on treatment prior to enrollment. Progressive disease for study entry is defined as any one or more of the following:
• PSA progression: minimum of two rising PSA values from a baseline measurement with an interval of \>= 1 week between each measurement. 2.0 ng/mL is the minimal starting value if PSA rise is only indication of progression.
• Soft tissue or visceral disease progression as per RECIST 1.1 criteria: increase \>= 20% in the sum of the diameter (SOD) (short axis for nodal lesions and long axis for non-nodal lesions) of all target lesions based on the smallest SOD since treatment started or the appearance of one or more new lesions.
• Bone progression: \>= 2 new lesions on bone scan.
• Patients must have adequate organ function (bone morrow reserve, hepatic function and renal function).

You may not qualify if:

• Previous treatment with Strontium-89, Samarium-153, Rhenium-186, Rhenium-188, Radium-223 or hemi-body irradiation.
• Any investigational agents within 28 days of study enrollment.
• Known hypersensitivity to the components of the study therapy or its analogues.
• Other concurrent cytotoxic chemotherapy, targeted therapy, biologic agents, immunotherapy, radioligand therapy, or investigational therapy.
• Transfusion for the sole purpose of eligibility into the study.
• Patients with a history of CNS metastases must have received therapy (surgery, radiotherapy, gamma knife) and be neurologically stable, asymptomatic, and not receiving corticosteroids for the purposes of maintaining neurologic integrity. Patients with epidural disease, canal disease and prior cord involvement are eligible if those areas have been treated, are stable, and not neurologically impaired.
• Symptomatic cord compression, or clinical or radiologic findings indicative of impending cord compression.
• Concurrent serious (as determined by the Principal Investigator) medical conditions, including, but not limited to, uncontrolled infection, active hepatitis B or C, or other significant co-morbid conditions that in the opinion of the investigator would impair study participation or cooperation.
• Diagnosed with other malignancies that are expected to alter life expectancy or may interfere with disease assessment. Patients with a prior history of malignancy who have been disease free for more than 3 years are eligible.
• Participants with an active documented COVID-19 infection (any grade of disease severity) at the time of informed consent may be included only when completely recovered (in accordance with local guidance).

Sponsors & Collaborators

• Endocyte: lead

Study Sites (2)

St. Vincent's Hospital Research Office-Translational Research Center

Darlinghurst, Australia

Location

Steve Biko Hospital-Department of Nuclear Medicine

Pretoria, South Africa

Location

MeSH Terms

Conditions

Prostatic Neoplasms, Castration-Resistant; Prostatic Neoplasms; Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Prostatic Diseases

Interventions

(225)Ac-PSMA-617; gallium 68 PSMA-11

Condition Hierarchy (Ancestors)

Genital Diseases; Urogenital Diseases; Male Urogenital Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Study-eligible participants with PSMA-positive, metastatic, castration resistant (mCRPC) prostate cancer will be assigned to one of three groups, A, B, and C based on their prior prostate cancer treatment history: 1. Group A: Men that have received prior cytotoxic chemotherapy and an ARPI, who Have Not been previously treated with prior 177Lu-PSMA-617 radioligand therapy or 177Lu-PSMA I\&T. 2. Group B: Men that Have Not received cytotoxic chemotherapies, ARPIs, and 177Lu-PSMA radioligand therapy or 177Lu-PSMA I\&T. Due to geographical differences in disease presentation/aggressiveness and access to treatment of mCRPC, group B participants will be enrolled only in South Africa, after medical review determines the need for therapy as part of a clinical study. 3. Group C: Men who HAVE been previously treated with 177Lu-PSMA-617 radioligand therapy or 177Lu-PSMA I\&T. Prior chemotherapy or ARPI is not required.

Study Record Dates

• First Submitted: September 29, 2020
• First Posted: October 22, 2020
• Study Start: April 1, 2021
• Primary Completion (Estimated): January 1, 2027
• Study Completion (Estimated): January 1, 2027
• Last Updated: April 30, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

ZA (1); AU (1)