Phase I Trial of 225Ac−J591 in Patients With mCRPC

This clinical trial is for men with advanced prostate cancer. The purpose of this study is to
find the highest dose level of the study drug, 225Ac-J591 that can be given without severe
side effects. The research study is being done because the standard treatments for prostate
cancer that has spread beyond the prostate gland are intended to minimize the adverse effects
of the disease. These treatments, however, are not curative. Patients who choose to
participate in this study will have a screening visit to determine whether or not they are
eligible to participate in the study. The treatment phase is comprised of 8 visits over
approximately 12 weeks. The study medication is called 225Ac-J591, and participants will
receive an infusion of the study drug on the Treatment visit of the study. During the other
study visits, participants will undergo routine tests and procedures, such as physical
examinations, and routine blood tests. Some blood tests will be done for research purposes
only, and participants will also undergo a research PET/CT scan at screening and end of
study. After completion of therapy, participants may be contacted on a periodic basis to see
how they are doing.

Key eligibility:

- Open to men age 18 and older.

- Diagnosis of progressive metastatic prostate cancer

- Have been previously treated for their disease with particular types of therapy.

Inclusion Criteria:

1. Histologically or cytologically confirmed adenocarcinoma of prostate

2. Documented progressive metastatic CRPC based on Prostate Cancer Working Group 3
(PCWG3) criteria, which includes at least one of the following criteria:

i. PSA progression ii. Objective radiographic progression in soft tissue iii. New bone
lesions

3. ECOG performance status of 0−2

4. Have serum testosterone < 50 ng/dL. Subjects must continue primary androgen
deprivation with an LHRH analogue (agonist/antagonist) if they have not undergone
bilateral orchiectomy.

5. Have previously been treated with at least one of the following:

i. Androgen receptor signaling inhibitor (such as enzalutamide) ii. CYP 17 inhibitor
(such as abiraterone acetate)

6. Have previously received taxane chemotherapy, been determined to be ineligible for
taxane chemotherapy by their physician, or refused taxane chemotherapy.

7. Age > 18 years

8. Patients must have normal organ and marrow function as defined below:

6.5.Absolute neutrophil count >2,000 cells/mm3 6.5.Hemoglobin ≥9 g/dL 6.5.Platelet
count >150,000 x 109/uL 6.5.Serum creatinine <1.5 x upper limit of normal (ULN) or
calculated creatinine clearance ≥ 60 mL/min/1.73 m2 by Cockcroft−Gault 6.5.Serum total
bilirubin <1.5 x ULN (unless due to Gilbert's syndrome in which case direct bilirubin
must be normal 6.5. Serum AST and ALT <1.5 x ULN

9. Ability to understand and the willingness to sign a written informed consent document.

Exclusion Criteria:

1. Implantation of investigational medical device ≤4 weeks of Cycle 1, Day 1 or current
enrollment in oncologic investigational drug or device study

2. 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

3. Prior systemic beta−emitting bone−seeking radioisotopes

4. Known active brain metastases or leptomeningeal disease

5. History of deep vein thrombosis and/or pulmonary embolus within 1 month of C1D1

6. 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

7. Radiation therapy for treatment of PC ≤4 weeks of Day 1 Cycle 1

8. 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.

9. 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

10. 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.

11. Known history of known myelodysplastic syndrome