225Ac-J591 Plus 177Lu-PSMA-I&T for mCRPC

• Status: Recruiting
• Trial end date: 2027-12-27
• Target enrollment: 0
• Participant gender: Male

Summary

This is a phase I/II dose-escalation study of 225Ac-J591 administered together with 177Lu-PSMA-I&T (also known as PNT2002). The two study drugs are 225Ac-J591 and 177Lu-PSMA-I&T. 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). The first phase of the study (phase I) will determine the highest dose of the study drug that can be safely given. The second phase of the study (phase II) will determine the effectiveness of the drug combination in patients with prostate cancer.

• Phase: Phase 1/Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Weill Medical College of Cornell University
• Collaborator: POINT Biopharma
• Treatments: Edetic Acid; Gallium 68 PSMA-11

Criteria

Inclusion Criteria:

• 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

Exclusion Criteria:

• 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

• Prior PSMA-targeted radionuclide therapy (prior PSMA-targeted isotopes used for imaging/diagnostic purposes are allowed, as is prior PSMA-targeted therapy that does not involve therapeutic radionuclides)

• 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