Use of an Experimental Radiopharmaceutical (131I-MIP-1095) in Men With Metastatic Castration-Resistant Prostate Cancer (mCRPC)

Inclusion Criteria:

- Males, age ≥18 years.

- Subjects must have histologically or cytologically confirmed adenocarcinoma of the
prostate

- Subjects must be castration resistant with evidence of progressive prostate cancer
despite castrate levels of testosterone (≤ 50 ng/dL) according to the PCWG3 criteria

- Subjects must have metastatic disease detectable by either bone scan or cross
sectional imaging by CT or MRI as per the PCWG3 guidelines

- Subjects must have progressive disease at study entry defined as 1 or more of the
following 3 criteria that occurred while the subject was on androgen deprivation
therapy:

- PSA progression defined by a minimum of two rising PSA levels with an interval of
≥1 week between each determination. Subjects who received an anti-androgen as
part of their primary hormonal therapy must demonstrate progression after
withdrawal. The PSA value at screening should be ≥ 2 μg/L (2 ng/mL).

- Soft tissue disease progression defined by RECIST 1.1

- Bone disease progression defined by PCWG3 with two or more new lesions on bone
scan.

Note: For subjects enrolling on the basis of soft tissue or bone progression, the baseline
scan must show progression relative to a comparison scan performed during prior therapy. If
the comparison scan is not available, the baseline scan report must reference the previous
scan to document progression

- Subjects who received combined androgen blockade as their first-line hormonal therapy
with an antiandrogen must have shown PSA progression after discontinuing the
antiandrogen for ≥ 6 weeks prior to study treatment. No washout is needed after
abiraterone or enzalutamide are discontinued. First generation antiandrogens such as
bicalutamide must be withdrawn if given as first-line therapy.

- ECOG Performance status of 0-1.

- Adequate organ reserve as evidenced by:

1. neutrophil count ≥ 1500 μL

2. platelet count ≥ 100,000/μL

3. hemoglobin ≥ 9.5 g/dL

4. total bilirubin level ≤1.5 x ULN

5. AST and ALT ≤2.5 x ULN

6. serum amylase ≤ ULN

7. lipase ≤ ULN

8. serum creatinine ≤1.5 x ULN or calculated creatinine clearance ≥ 60 mL/min
(Cockroft Gault equation)

9. clearance of 99mTc MAG3 within 1.5 x ULN and no evidence of obstruction on the
scan.

- Serum albumin of > 3.0 g/dL

- Subjects must have received, were ineligible to receive, or refused at least one
cytotoxic chemotherapy and enzalutamide or abiraterone or both enzalutamide and
abiraterone.

- Subjects must agree to use a medically acceptable method of birth control (e.g.,
spermicide in conjunction with a barrier such as a condom) or sexual abstinence for
the duration of the study, including 30 days after the last dose of study drug. Sperm
donation is prohibited during the study and for 30 days after the last dose of study
drug. Female partners must use hormonal or barrier contraception unless postmenopausal
or abstinent.

- Life expectancy ≥ 6 months

Exclusion Criteria:

- Subject has predominant histologically or cytologically confirmed neuroendocrine
prostate cancer (mixed histology is permissible, as is positivity of serum CgA and
CEA).

- Subject has received an investigational therapeutic agent for prostate cancer within 4
weeks prior to the administration of 131I-MIP-1095.

- Subject who has not recovered from the effects of any major surgery prior to initial
treatment

- Subject has received treatment with a systemic therapeutic radioisotope (89Sr, 223Ra
dichloride, 153Sm-lexidronam) or has received prior external beam radiation therapy
(EBRT) of the head and/or neck.

- Subject is currently on renal dialysis

- Subject has started treatment with denosumab < 1 month prior to study entry. Subjects
are allowed to be on bisphosphonates or denosumab provided they are on a stable dose
for ≥ 4 weeks before administration of study drug

- Subject using chronic systemic steroids greater than the equivalent of 10 mg of
prednisone/prednisolone per day in the 2 weeks preceding study entry ; replacement
doses of steroids, topical, inhalational, nasal and ophthalmic steroids are permitted.

- Diagnosis of other invasive malignancies within the preceding 3 years prior to
screening with > 30% likelihood of relapse within the next 3 years, except
non-melanoma skin cancer and non-muscle invasive urothelial cancer

- Any other serious illness or medical condition or social circumstance that might
interfere with the subject's participation in the trial or interfere with the
interpretation of the results, including, but not limited to:

1. any uncontrolled infection

2. NYHA Class III or Class IV heart failure

3. unstable angina

4. myocardial infarction within the 6 months prior to study entry

5. uncontrolled hypertension (systolic BP > 160 mmHg despite 2 antihypertensive
medications)

6. COPD requiring hospital admission in the year prior to study entry

7. diabetes mellitus requiring hospital admission in the year prior to study entry

8. chronic liver disease

9. hypothyroidism (TSH level > 3.0 mIU/L)

10. substance abuse

- Unable or unwilling to follow post-therapy radiation protection procedures