IMMU-132 in Patients With Metastatic Castration-Resistant Prostate Cancer Progressing on Second Generation AR-Directed Therapy

This study will investigate the safety and efficacy of IMMU-132 in patients with metastatic
castration-resistant prostate cancer progressing on abiraterone or enzalutamide. Patients who
have progressed while on therapy with combination enzalutamide/abiraterone or
ARN-509/abiraterone as part of ongoing clinical trials are allowed and may be enrolled in the
study. To better understand the heterogeneity of response and in particular to identify
patients likely to benefit, an extensive correlative biomarker program will be included to
collect and analyze tumor tissue biopsies, circulating tumor cells (CTCs), and circulating
tumor DNA (ctDNA).

A validated predictive biomarker would benefit the individual patient by enabling him to be
treated with a safe effective oral drug and avoid one from which he is unlikely to benefit.
It is also essential for prostate cancer drug development because the increasing availability
of more life-prolonging therapies is making it more difficult to prove a survival benefit for
the next promising agent.

Inclusion Criteria:

- Documented histological or cytological evidence of adenocarcinoma of the prostate

- Documented metastatic disease on bone scan and/or CT scans

- Received enzalutamide, abiraterone, or apalutamide. Subjects who have received
combination enzalutamide/abiraterone or combination ARN-509/abiraterone as part of
ongoing clinical trials are allowed. Subjects who have received TAK-700 (Orteronel®),
TOK-001 (Galeterone®), or any other therapeutic investigational product directed
towards the AR or androgen biosynthesis are allowed. Prior treatment with
first-generation AR antagonists (i.e., bicalutamide, nilutamide, flutamide) before
second generation AR-directed therapy is allowed.

- Demonstrated disease progression while on enzalutamide, apalutamide, and/or
abiraterone. Progressive disease is defined by one or more of the following:

- A rise in PSA on two successive determinations at least one week apart and PSA
level ≥2 ng/mL

- Soft-tissue progression defined by RECIST 1.1

- Bone disease progression defined by PCWG2 with ≥2 new lesions on bone scan

- A minimum serum PSA level of ≥2 ng/mL that is rising based on the PCWG2 criteria

- ≥18 y ears of age

- Castrate levels of testosterone (<50 ng/dL [1.74 nmol/L])

- Undergone orchiectomy, or have been on LHRH agonists or antagonists, for at least 3
months prior to study treatment start. Subjects on LHRH agonists/antagonists must
remain on these agents for the duration of the study

- ECOG Performance Status of 0-1 (Appendix A)

- Normal organ function with acceptable initial laboratory values within 30 days of
study treatment start:

- WBC ≥3000/μl

- ANC ≥1000/μl

- Platelet count ≥100,000/μl

- HGB ≥9 g/dL

- Adequate hepatic function as evidenced by AST/ALT levels <3X the ULN and bilirubin
levels of <2.0 mg/dl.

- Adequate renal function as evidenced by serum creatinine of <2.0 mg/dL

- Able to provide written informed consent, or have a legal representative provide
written informed consent

- Discontinued enzalutamide, apalutamide, or abiraterone ≥4 weeks prior to study drug
initiation

- Subjects must have a previously-acquired biopsy from a metastatic site available

- Subjects must be willing and able (in the opinion of the treating physician) to
undergo one research biopsy for the investigational component of this study

- Subjects who have partners of child-bearing potential must be willing to use at least
two forms of effective birth control (one form must be a barrier method) during the
treatment period and for 90 days after last dose of IMMU-132. Subjects must also agree
to not donate sperm through 90 days following the last dose of IMMU-132.

Exclusion Criteria:

- Received prior cytotoxic chemotherapy for CRPC. Prior docetaxel for
castration-sensitive disease is permitted.

- Received more than one second generation, FDA approved, AR-directed line of therapy:
i.e., sequential enzalutamide-abiraterone or abiraterone-enzalutamide will not be
allowed.

- Completed sipuleucel-T (Provenge ®) treatment within 30 days of study treatment start.

- Received any therapeutic investigational agent within 2 weeks of study treatment
start.

- Received palliative radiotherapy within 4 weeks of study treatment start.

- Received herbal products or alternative therapies that may decrease PSA levels or that
may have hormonal anti-prostate cancer activity (e.g., saw palmetto, PC-SPES, PC-HOPE,
St. John's wort, selenium supplements, grape seed extract, etc.) within 4 weeks of
study treatment start or plans to initiate treatment with these products/alternative
therapies during the entire duration of the study.

- Active CNS metastases from prostate cancer. Subjects with treated epidural disease are
eligible to enroll. Subjects with treated brain metastases can be included as long as
>4 weeks have elapsed since last treatment (radiotherapy or surgery) for brain
metastases, the subject is neurologically and radiographically stable, and is not
receiving corticosteroids for brain metastases. Subjects with untreated brain
metastases are excluded. Brain imaging (CT or MRI) is not required at baseline if
brain metastases are not clinically suspected.

- A history within the last 3 years of another invasive malignancy (excluding
non-melanoma skin cancer).

- A QTcF interval of >470 msec on the initial Screening ECG; if the Screening ECG QTcF
interval is >470 msec, then it may be repeated two more times, and if the mean QTcF of
the 3 ECGs is ≤470 msec, the subject may be enrolled.

- A history of clinically significant cardiac arrhythmias including ventricular
tachycardia, ventricular fibrillation, torsades de pointes and second degree or third
degree atrioventricular heart block without a permanent pacemaker in place. Subjects
with resolved or rate-controlled atrial fibrillation/atrial flutter are allowed.

- NYHA Class III or IV congestive heart failure, unstable angina, myocardial
infarction/acute coronary syndrome within the preceding 6 months.

- Diabetes mellitus with more than 2 episodes of diabetic ketoacidosis in the 12 months
preceding study treatment start.

- Inadequately controlled hypertension (defined as blood pressure >150mmHg systolic
and/or >100 mmHg diastolic despite antihypertensive medication) or any history of
hypertensive crisis or hypertensive encephalopathy.

- History of loss of consciousness or transient ischemic attack within 12 months before
study treatment start.

- Known active HIV, Hepatitis B, or Hepatitis C infections.

- Any other medical, psychiatric, or social condition, including substance abuse, which
in the opinion of the Investigator would preclude safe participation in the study.