Recruiting
Phase 1

225Ac-J591 & 177Lu-PSMA

Sponsor:

Weill Medical College of Cornell University

Code:

NCT04886986

Conditions

Prostate Cancer

Eligibility Criteria

Sex: Male

Age: 18 - 70+

Healthy Volunteers: Not accepted

Interventions

225Ac-J591

177Lu-PSMA-617

68Ga-PSMA-11

177Lu-PSMA-I&T

Study Details

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

Study ID

NCT04886986

Start date

Jun 30, 2021

Status verified date

Jun, 2026

Completion date

Dec, 2029

Anticipated

Primary completion date

Dec, 2027

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: Male

Age: 18 - 70+

Healthy Volunteers: Not accepted

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
  • 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

Study Design

Enrollment

42 participants

Anticipated

Allocation

Non randomized

Intervention Model

Single group

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

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

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

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

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

Interventions

225Ac-J591

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

177Lu-PSMA-617

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

68Ga-PSMA-11

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

177Lu-PSMA-I&T

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

Primary outcome measure

  • Dose limiting toxicity (DLT) of 225Ac-J591 and 177Lu-PSMA small molecule [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: From Cycle 1 Visit 1 up to end of study, approximately 3 years (each cycle is 8 weeks). ]

Central Contacts and Locations

Central contacts

GUONC Research Team

212-746-1480guonc@med.cornell.edu

Locations

Brooklyn Methodist Hospital - New York Presbyterian

Recruiting

Brooklyn, New York, United States, 11215

Contacts

Lina Flores, RN

646-923-5883lif9061@nyp.org

Principal Investigator:

David Nanus, MD

Weill Cornell Medicine New York Presbyterian

Recruiting

New York, New York, United States, 10065

Contacts

GUONC Research Team

guonc@med.cornell.edu

Principal Investigator:

Joseph Osborne, MD

More Information

Sponsor

Weill Medical College of Cornell University

Last update posted

Jun 11, 2026

Last verified

Jun, 2026

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-10. This information was provided to ClinicalTrials.gov by Weill Medical College of Cornell University on 2026-06-11.