Fractionated and Multiple Dose 225Ac-J591 for Progressive mCRPC

NCT04506567 | Active Not Recruiting Phase 1 Results DMC FDA Drug

• 1 other identifier: 20-01021288
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 2

Brief Summary

The purpose of the initial (phase I) portion of this study is to find a dose level and administration schedule of the study drug, 225Ac-J591, that can be given without severe side effects. The purpose of the second (phase II) portion of the study is to determine the proportion of those with PSMA-positive tumors with \>50% PSA decline following 225Ac-J591 treatment in two regimens.

Conditions

Prostate Cancer

Outcome Measures

Primary Outcomes (4)

• Number of Participants With Dose Limiting Toxicity (DLT)

  DLTs will be measured by utilizing the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.

  Collected from Day 1 through 6 months

• Maximum Tolerated Dose (MTD)

  The dose that produces an "acceptable" level of toxicity or that, if exceeded, would put subjects at "unacceptable" risk for toxicity. MTD is defined as the dose level at which no more than two patients out of six experienced dose-limiting toxicity (DLT).

  Collected from Day 1 through 6 months

• Recommended Phase II Dose (RP2D) of 225Ac-J591 in Fractionated Dose and Multiple Dose Regimens Both Pre- and Post-treatment With 177Lu-PSMA-RL

  Collected from Day 1 through 6 months

• Number of Participants With PSMA-positive Tumors With >50% PSA Decline Following 225Ac-J591 in Each Cohort Regimen

  Number of participants achieving greater than 50% PSA decline (relative to baseline/pre-treatment PSA). Response may occur at any time following treatment initiation and prior to going off study or initiation of new therapy

  Collected from Day 1 through 6 months

Secondary Outcomes (7)

• Number of Participants With Radiographic Response

  Imaging performed at timepoints from Day 1 through study completion, approximately 3 years.

• Overall Survival Following 225Ac-J591 Treatment

  Collected from Day 1 through study completion, approximately 3 years.

• Change in Disease Assessment With 68Ga-PSMA-11 PET/CT Prior to and Following Investigational Treatment

  Scans performed during screening period (within 30 days of Cycle 1 Day 1) and at Day 85 from Cycle 1 Day 1.

• Number of Participants With Change in Circulating Tumor Cells (CTC) Count at 12 Weeks Following 225Ac-J591

  Samples will be collected at Screening and Day 85

• Number of Participants With Adverse Events

  Collected from Day 1 through study completion, approximately 3 years

Study Arms (9)

Multiple Dose 45 KBq/kg

EXPERIMENTAL

Participants in this multiple dose cohort received 45 KBq/Kg of 225Ac-J591 every 6 weeks, up to 4 cycles.

Drug: Multiple Dose of 225Ac-J591 at 45 KBq/kg; Diagnostic Test: 68Ga-PSMA-HBED-CC injection

Multiple Dose 55 KBq/kg

EXPERIMENTAL

Participants in this multiple dose cohort received 55 KBq/Kg of 225Ac-J591 every 6 weeks, up to 4 cycles.

Drug: Multiple Dose of 225Ac-J591 at 55 KBq/kg; Diagnostic Test: 68Ga-PSMA-HBED-CC injection

Multiple Dose 65 KBq/kg

EXPERIMENTAL

Participants in this multiple dose cohort received 65 KBq/Kg of 225Ac-J591 every 6 weeks, up to 4 cycles.

Drug: Multiple Dose of 225Ac-J591 at 65 KBq/kg; Diagnostic Test: 68Ga-PSMA-HBED-CC injection

Fractionated Dose 45 KBq/kg

EXPERIMENTAL

Participants in this cohort received a single cycle of 45 KBq/kg of 225Ac-J591, administered as a fractionated dose on days 1 and 15.

Drug: Fractionated Dose of 225Ac-J591 at 45 KBq/kg; Diagnostic Test: 68Ga-PSMA-HBED-CC injection

Fractionated Dose 55 KBq/kg

EXPERIMENTAL

Participants in this cohort received a single cycle of 55 KBq/kg of 225Ac-J591, administered as a fractionated dose on days 1 and 15.

Drug: Fractionated Dose of 225Ac-J591 at 55 KBq/kg; Diagnostic Test: 68Ga-PSMA-HBED-CC injection

Fractionated Dose 60 KBq/kg

EXPERIMENTAL

Participants in this cohort receive a single cycle of 60 KBq/kg of 225Ac-J591, administered as a fractionated dose on days 1 and 15. This was also the dose level for the expansion cohort of fractionated dose regimen.

Drug: Fractionated Dose of 225Ac-J591 at 60 KBq/kg; Diagnostic Test: 68Ga-PSMA-HBED-CC injection

Fractionated Dose 65 KBq/kg

EXPERIMENTAL

Participant in this cohort receive a single cycle of 65 KBq/kg of 225Ac-J591, administered as a fractionated dose on days 1 and 15.

Drug: Fractionated Dose of 225Ac-J591 at 65 KBq/kg; Diagnostic Test: 68Ga-PSMA-HBED-CC injection

Fractionated Dose (prior 177Lu-PSMA-RL) 45 KBq/kg

EXPERIMENTAL

Participants in this cohort, who were previously treated with 177Lu-PSMA-RL, received a single cycle of 45 KBq/kg of 225Ac-J591, administered as a fractionated dose on days 1 and 15.

Drug: Fractionated Dose of 225Ac-J591 at 45 KBq/kg (Prior 177Lu-PSMA-RL); Diagnostic Test: 68Ga-PSMA-HBED-CC injection

Fractionated Dose (prior 177Lu-PSMA-RL) 50 KBq/kg

EXPERIMENTAL

Participants in this cohort, who were previously treated with 177Lu-PSMA-RL, received a single cycle of 50 KBq/kg of 225Ac-J591, administered as a fractionated dose on days 1 and 15.

Drug: Fractionated Dose of 225Ac-J591 at 50 KBq/kg (Prior 177Lu-PSMA-RL); Diagnostic Test: 68Ga-PSMA-HBED-CC injection

Interventions

68Ga-PSMA-HBED-CC injection DIAGNOSTIC_TEST

68Ga-PSMA-HBED-CC PET/CT before and after treatment

Fractionated Dose (prior 177Lu-PSMA-RL) 45 KBq/kg; Fractionated Dose (prior 177Lu-PSMA-RL) 50 KBq/kg; Fractionated Dose 45 KBq/kg; Fractionated Dose 55 KBq/kg; Fractionated Dose 60 KBq/kg; Fractionated Dose 65 KBq/kg; Multiple Dose 45 KBq/kg; Multiple Dose 55 KBq/kg; Multiple Dose 65 KBq/kg

Multiple Dose of 225Ac-J591 at 45 KBq/kg DRUG

Multiple dose of 45 KBq/kg

Multiple Dose 45 KBq/kg

Multiple Dose of 225Ac-J591 at 55 KBq/kg DRUG

Multiple dose of 55 KBq/kg in dose-escalation regimen

Multiple Dose 55 KBq/kg

Multiple Dose of 225Ac-J591 at 65 KBq/kg DRUG

Multiple dose of 65 KBq/kg in dose-escalation regimen

Multiple Dose 65 KBq/kg

Fractionated Dose of 225Ac-J591 at 45 KBq/kg DRUG

Fractionated dose of 45 KBq/kg in dose-escalation regimen

Fractionated Dose 45 KBq/kg

Fractionated Dose of 225Ac-J591 at 55 KBq/kg DRUG

Fractionated dose of 55 KBq/kg in dose-escalation regimen

Fractionated Dose 55 KBq/kg

Fractionated Dose of 225Ac-J591 at 60 KBq/kg DRUG

Fractionated dose of 60 KBq/kg in dose-escalation and dose-expansion regimens

Fractionated Dose 60 KBq/kg

Fractionated Dose of 225Ac-J591 at 65 KBq/kg DRUG

Fractionated dose of 65 KBq/kg in dose-escalation regimen

Fractionated Dose 65 KBq/kg

Fractionated Dose of 225Ac-J591 at 50 KBq/kg (Prior 177Lu-PSMA-RL) DRUG

Fractionated dose of 50 KBq/kg for cohort of participants previously treated with 177Lu-PSMA-RL

Fractionated Dose (prior 177Lu-PSMA-RL) 50 KBq/kg

Fractionated Dose of 225Ac-J591 at 45 KBq/kg (Prior 177Lu-PSMA-RL) DRUG

Fractionated dose of 45 KBq/kg for cohort of participants previously treated with 177Lu-PSMA-RL

Fractionated Dose (prior 177Lu-PSMA-RL) 45 KBq/kg

Eligibility Criteria

• Age: 18 Years - 99 Years
• Gender Eligibility Details: Adult male patients of \>18 years age with documented progressive metastatic CRPC
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically or cytologically confirmed adenocarcinoma of prostate
• Documented progressive metastatic CRPC based on Prostate Cancer Working
• Group 3 (PCWG3) criteria, which includes at least one of the following criteria:
• PSA progression
• Objective radiographic progression in soft tissue
• New bone lesions
• Have serum testosterone \< 50 ng/dL. Subjects must continue primary androgen deprivation with an LHRH/GnRH analogue (agonist/antagonist) if they have not undergone orchiectomy
• Have previously been treated with at least one of the following in any disease state:
• Androgen receptor signaling inhibitor (such as enzalutamide)
• CYP 17 inhibitor (such as abiraterone acetate)
• Have previously received taxane chemotherapy (in any disease state), been determined to be ineligible for taxane chemotherapy by their physician, or refused taxane chemotherapy.
• Age \> 18 years
• Patients must have normal organ and marrow function as defined below:
• Absolute neutrophil count \>2,000 cells/mm3
• Hemoglobin ≥9 g/dL

You may not qualify if:

• Implantation of investigational medical device ≤4 weeks of Treatment Visit 1 (Day 1) or current enrollment in oncologic investigational drug or device study
• Use of investigational drugs ≤4 weeks or \<5 half-lives of Cycle 1, Day 1 or current enrollment in investigational oncology drug or device study
• Prior systemic beta-emitting bone-seeking radioisotopes (e.g. samarium-153, strontium-89)
• For patients enrolled in the post-177Lu-PSMA-RL cohorts: prior radium-223
• Untreated hydronephrosis
• Known active brain metastases or leptomeningeal disease
• History of deep vein thrombosis and/or pulmonary embolus within 1 month of C1D1
• Other serious illness(es) involving the cardiac, respiratory, CNS, renal, hepatic or hematological organ systems which might preclude completion of this study or interfere with determination of causality of any adverse effects experienced in this study
• Radiation therapy for treatment of PC ≤4 weeks of Day 1 Cycle 1
• Chemotherapy for treatment of PC ≤4 weeks of Day 1 Cycle 1
• Patients on stable dose of bisphosphonates or denosumab, which have been started no less than 4 weeks prior to treatment start, may continue on this medication, however patients are not allowed to initiate bisphosphonate/Denosumab therapy during the DLT-assessment period of the study
• Having partners of childbearing potential and not willing to use a method of birth control deemed acceptable by the principle investigator and chairperson during the study and for 1 month after last study drug administration
• Currently active other malignancy other than non-melanoma skin cancer. Patients are considered not to have "currently active" malignancy if they have completed any necessary therapy and are considered by their physician to be at less than 30% risk of relapse
• Known history of myelodysplastic syndrome
• Bone scan with confluent lesions and lack of urinary tracer consistent with a "superscan" as determined by the investigator

Sponsors & Collaborators

• Weill Medical College of Cornell University: lead

Study Sites (2)

Brooklyn Methodist Hospital - New York Presbyterian

Brooklyn, New York, 11215, United States

Location

Weill Cornell Medicine

New York, New York, 10065, United States

Location

Related Publications (1)

• Stangl-Kremser J, Ricaurte-Fajardo A, Huicochea Castellanos S, Martinez-Fundichely A, Sun M, Osborne JR, Nauseef JT, Tagawa ST, Bander NH. Baseline Imaging Derived Factors of Response Following [225Ac]Ac-J591 Therapy in Metastatic Castration-Resistant Prostate Cancer: A Lesion Level Analysis. Prostate. 2025 Apr;85(5):502-509. doi: 10.1002/pros.24853. Epub 2025 Jan 23.

  PMID: 39853781 DERIVED

MeSH Terms

Conditions

Prostatic Neoplasms

Condition Hierarchy (Ancestors)

Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases

Results Point of Contact

• Title: Dr. Scott Tagawa
• Organization: Weill Cornell Medicine

stt2007@med.cornell.edu

646-962-2072

Study Officials

• Joseph R Osborne, MD

  Weill Medical College of Cornell University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

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

Model Details: Participants were enrolled to either the multiple dose cohort or the fractionated dose cohort in parallel, after which additional participants were enrolled in a prospective fractionated dose regimen (with prior 177Lu-PSMA-RL) and additional participants were enrolled in an expansion cohort of fractionated dose regimen at the R2PD of 60 KBq/kg. In a fractionated dose cohort, participants receive the dose level of treatment during one cycle to be administered on Day 1 and Day 15. In the multiple dose cohort, participants receive the dose level of treatment administered as a single dose per cycle every 6 weeks up to 4 cycles.

Study Record Dates

• First Submitted: August 6, 2020
• First Posted: August 10, 2020
• Study Start: August 18, 2020
• Primary Completion: June 1, 2025
• Study Completion (Estimated): December 1, 2026
• Last Updated: August 19, 2026
• Results First Posted: August 19, 2026

Record last verified: 2026-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)