Phase I Study of 225Ac-J591 Plus 177Lu-PSMA Small Molecule for Progressive Metastatic Castration Resistant Prostate Cancer

NCT04886986 | Active Not Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: 20-08022486
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 2

Brief Summary

This is a phase I dose-escalation study of 225Ac-J591 administered together with 177Lu-PSMA small molecule. Both drugs are designed to deliver radiation to prostate cancer cells; they are known as radionuclide conjugates (radiation linked to antibodies/molecules that recognize prostate cancer cells). This phase of the study (phase I) will determine the highest dose of the study intervention that can be safely given.

Conditions

Prostate Cancer

Outcome Measures

Primary Outcomes (3)

• Dose limiting toxicity (DLT) of 225Ac-J591 and 177Lu-PSMA small molecule

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

  From Cycle 1 Day 1 up to 12 weeks after Cycle 1 Day 1 (each cycle is 8 weeks).

• Cumulative maximum tolerated dose (MTD) or recommended phase II dose 225Ac-J591 and 177Lu-PSMA small molecule

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

  From Cycle 1 Day 1 up to 12 weeks after Cycle 1 Day 1 (each cycle is 8 weeks).

• Proportion of PSMA+ subjects (by imaging criteria) with >50% PSA decline following treatment with the combination of 225Ac-J591 and 177Lu-PSMA small molecule

  Proportion of patients achieving 50% or greater 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.

  From Cycle 1 Visit 1 up to end of study, approximately 3 years (each cycle is 8 weeks).

Secondary Outcomes (6)

• Change in biochemical progression-free survival

  From Cycle 1 Visit 1 up to end of study, approximately 3 years (each cycle is 8 weeks).

• Change in circulating tumor cells (CTC) count

  Samples will be collected at screening, week 12, week 24.

• Number of participants with radiographic response

  Patients will undergo imaging at screening, week 12, and week 24.

• Number of participants with adverse events

  From Cycle 1 Visit 1 up to end of study, approximately 3 years (each cycle is 8 weeks).

• Overall survival following treatment with 225Ac-J591 and 177Lu-PSMA small molecule

  From Cycle 1 Visit 1 up to end of study, approximately 3 years (each cycle is 8 weeks).

Study Arms (2)

Combination of 225Ac-J591 and 177Lu-PSMA-I&T

EXPERIMENTAL

Participants who received the combination of 225Ac-J591 and 177Lu-PSMA-I\&T, along with 68Ga-PSMA-11.

Drug: 225Ac-J591; Drug: 68Ga-PSMA-11; Drug: 177Lu-PSMA-I&T

Combination of 225Ac-J591 and 177Lu-PSMA-617

EXPERIMENTAL

Participants will receive the study drugs 225Ac-J591 and 177Lu-PSMA-617, along with 68Ga-PSMA-11.

Drug: 225Ac-J591; Drug: 177Lu-PSMA-617; Drug: 68Ga-PSMA-11

Interventions

225Ac-J591 DRUG

30 - 40 KBq/kg (dose-escalation) every 8 weeks, for up to 2 cycles. Administered together with 177Lu-PSMA-617. Intravenous administration.

Combination of 225Ac-J591 and 177Lu-PSMA-617; Combination of 225Ac-J591 and 177Lu-PSMA-I&T

177Lu-PSMA-I&T DRUG

6.8 GBq received every 8 weeks, up to 2 cycles. Administered together with 225Ac-J591. Intravenous administration.

Combination of 225Ac-J591 and 177Lu-PSMA-I&T

68Ga-PSMA-11 DRUG

\[185 ±74 MBq or 5 ±2 mCi\] intravenous during screening, 12 weeks, 24 weeks. Imaging agent for PSMA PET/CT.

Also known as: 68Ga-PSMA-HBED-CC

Combination of 225Ac-J591 and 177Lu-PSMA-617; Combination of 225Ac-J591 and 177Lu-PSMA-I&T

177Lu-PSMA-617 DRUG

6.8 - 7.4 GBq received every 8 weeks, for up to 2 cycles. Administered together with 225Ac-J591. Intravenous administration.

Combination of 225Ac-J591 and 177Lu-PSMA-617

Eligibility Criteria

• Age: 18 Years - 99 Years
• Gender Eligibility Details: Metastatic Castrate Resistant Prostate Cancer
• 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
• ECOG performance status of 0-2
• Have serum testosterone \< 50 ng/dL. Subjects must continue primary androgen deprivation with an LHRH/GnRH analogue (agonist/antagonist) if they have not undergone bilateral orchiectomy
• Have previously been treated with at least one of the following: Androgen receptor signaling inhibitor (such as enzalutamide), CYP 17 inhibitor (such as abiraterone acetate)
• Have previously received taxane chemotherapy, 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, Platelet count: \>150,000 x 109/uL, Serum creatinine: \<1.5 x upper limit of normal (ULN) or calculated creatinine clearance ≥ 60 mL/min/1.73 m2 by Cockcroft-Gault, Serum total bilirubin: \<1.5 x ULN (unless due to Gilbert's syndrome in which case direct bilirubin must be normal), Serum AST and ALT: \<1.5 x ULN in the absence of liver metastases; \<3 x ULN if due to liver metastases (in both circumstances bilirubin must meet entry criteria)
• Ability to understand, and the willingness to sign, a written informed consent document

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 Treatment visit # 1(Day 1) or current enrollment in investigational oncology drug or device study
• Prior systemic beta-emitting bone-seeking radioisotopes. Prior radium-223 is allowed provided at least 90 days have lapsed since last dose
• For the prior PSMA-TRT-naive cohort, prior PSMA-targeted radionuclide therapy is not allowed (prior PSMA-targeted isotopes used for imaging/diagnostic purposes are allowed, as is prior PSMA-targeted therapy that does not involve therapeutic radionuclides); For the 177Lu-PSMA small molecule exposed cohort, no dose limiting toxicity may have been observed during/after therapy with prior treatment and all other entry criteria must be met
• Known active brain or leptomeningeal metastases
• History of deep vein thrombosis and/or pulmonary embolus within 1 month of Treatment visit #1
• 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 Treatment visit #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 at least 140 days 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
• Prior exposure to PARP inhibitor \> 2 weeks

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 Presbyterian

New York, New York, 10065, United States

Location

MeSH Terms

Conditions

Prostatic Neoplasms

Interventions

Pluvicto; gallium 68 PSMA-11

Condition Hierarchy (Ancestors)

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

Study Officials

• Joseph Osborne, MD

  Weill Medical College of Cornell University

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: May 11, 2021
• First Posted: May 14, 2021
• Study Start: June 30, 2021
• Primary Completion (Estimated): December 1, 2027
• Study Completion (Estimated): December 1, 2029
• Last Updated: March 31, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)