Phase 1 of EC1169 In Patients With Recurrent MCRPC

This is a Phase 1, multicenter, open-label, non-randomized, oncology study to conducted in 2
parts. Part A is a dose-escalation phase to determine the Recommended Phase 2 (RP2) dose and
the following :

- Evaluate the administration of EC1169 QW on Weeks 1 and 2 of a 3-week schedule

- Evaluate the safety and pharmacokinetic profile of EC1169 and EC0652

- To assess preliminary efficacy results in patients with metastatic, castration-resistant
prostate cancer (mCRPC) who have progressed on abiraterone and/or enzalutamide, and
previously treated with a taxane.

The primary objective of Part B is to identify the radiographic progression-free survival
(rPFS) in taxane-naïve and taxane-exposed PSMA-positive mCRPC patients receiving treatment
with EC1169.

Inclusion Criteria:

- Patients must have the ability to sign an approved informed consent form (ICF).

- Patients must be ≥ 18 years of age.

- Patients must have histological, pathological and/or cytological confirmation of
prostate cancer.

- Patients must have progressive, metastatic, castration-resistant prostate cancer
(mCRPC) as defined below:

- Documented progressive metastatic CRPC will be based on at least one of the following
criteria:

- PSA progression defined as 25% increase over baseline value with an increase in
the absolute value of at least 2 ng/mL that is confirmed by another PSA level
with a minimum of a 1 week interval and a minimum PSA of 2 ng/mL.

- Soft-tissue progression defined as an increase ≥ 20% in the sum of the longest
diameter (LD) of all target lesions based on the smallest sum LD since treatment
started or the appearance of one or more new lesions.

- Progression of bone disease (evaluable disease) or (new bone lesion(s)) by bone
scan.

- Patients must have prior and/or ongoing androgen-deprivation therapy and a castrate
level of serum testosterone (<50 ng/dL).

- Patients must have progressed on abiraterone and/or enzalutamide.

- Patients must have been previously treated with a taxane except in cases of
contraindication (e.g. poor performance status, age or patient choice)

- Patients must have an Eastern Cooperative Oncology Group (ECOG) performance status of
0 or 1.

- Patients must have at least one measurable lesion that can be followed for response
assessment on baseline imaging obtained no more than 28 days prior to beginning study
therapy. Baseline and follow up radiological disease assessment must include bone
scans performed with either Technetium-99m labeled diphosphonates or Fluorine-18
sodium fluoride PET or PET/CT, as per the local standard of care for patients with
prostate cancer.

- Patients with CNS metastases that are symptomatic must have received therapy (surgery,
XRT, gamma knife) and be neurologically stable and off of steroids. The patient should
be off steroids at least 14 days before pre-registration. Asymptomatic CNS metastatic
disease without associated edema, shift, requirement for steroids or anti-seizure
medications are eligible after discussion with the sponsor medical monitor. For
patients with a history of CNS metastasis, baseline and subsequent radiological
imaging must include evaluation of the brain (MRI preferred or CT with contrast)

- Patients must have recovered (to baseline/stabilization) from prior therapy-associated
acute toxicities.

- Patients with prior radiation therapy are eligible if they meet the following
criteria:

- Prior radiotherapy must be completed at least 4 weeks before patient begins study
therapy.

- Patient must have recovered from the acute toxic effects of the treatment before
beginning study therapy.

- Patients must have adequate organ function:

- Bone marrow reserve: Absolute neutrophil count (ANC) ≥ 1.5 x 109/L. Platelets ≥
100 x 109/L. Hemoglobin ≥ 9 g/dL.

- Cardiac:

- Left ventricular ejection fraction (LVEF) equal to or greater than the
institutional lower limit of normal. LVEF must be evaluated within 28 days prior
to beginning study therapy.

- Cardiac Troponin I within normal limit.

- Hepatic: Total bilirubin ≤ 1.5 x the upper limit of normal (ULN). Alanine
aminotransferase (ALT), aspartate aminotransferase (AST) ≤ 3.0 x ULN OR ≤ 5.0 x ULN
for patients with liver metastases.

- Renal: Serum creatinine ≤ 1.5 x ULN, or for patients with serum creatinine > 1.5 ULN,
creatinine clearance ≥ 50 mL/min.

Exclusion Criteria:

- More than 3 prior systemic anti-cancer therapies (e.g. cytotoxic agents, biologic
agents) regimens for metastatic disease

- Previous treatment with Samarium-153 or Strontium-89.

- Any systemic anti-cancer therapy (e.g. chemotherapy, immunotherapy or biological
therapy [including monoclonal antibodies]) within 28 days prior to beginning study
therapy.

- Known hypersensitivity to the components of the study therapy or its analogs.

- Carcinomatous meningitis and/or symptomatic central nervous system (CNS) metastases.

- Malignancies that are expected to alter life expectancy or may interfere with disease
assessment. Patients with adequately treated non-melanoma skin cancer and patients
with prior history of malignancy who have been disease free for more than 3 years are
eligible.

- Neuropathy CTCAE grade > 2

- QTc interval of > 480 ms.

- History of ischemic cardiac disease that has occurred within 6 months prior to study
entry.

- Any other serious cardiac illness or medical conditions such as unstable angina,
pulmonary embolism, or uncontrolled hypertension.

- Other concurrent chemotherapy, immunotherapy, radiotherapy, or investigational
therapy.

- Active uncontrolled infections

- Known active Hepatitis B or C infections

Inclusion Criteria for Part B:

To qualify for enrollment, the following criteria must be met:

1. Patients must have the ability to understand, and have signed an approved ICF

2. Patients must be males ≥ 18 years of age

3. Patients must have histological, pathological and/or cytological confirmation of
prostate cancer

4. Patients must have progressive mCRPC defined by meeting at least one of the following
criteria:

1. PSA progression defined as 25% increase over a baseline value of > 2 ng/ml with
an increase in the absolute value of at least 2 ng/mL that is confirmed by
another PSA level with a minimum of a 1-week interval. Baseline is defined as the
PSA nadir level since commencing most recent prior therapy

2. Soft-tissue progression defined as an increase ≥ 20% in the sum of the diameter
(SOD; short axis for nodal lesions and long axis for non-nodal lesions) of all
target lesions based on the smallest SOD, or the appearance of one or more new
lesions, since the onset of the most recent prior therapy

3. Progression of bone disease according to PCWG3 criteria

5. Patients must have a castrate level of serum testosterone (< 50 ng/dL)

6. For inclusion in Cohort 1, mCRPC patients must have progressed while receiving (or
subsequent to receiving) abiraterone and/or enzalutamide but must not have previously
received taxane-based systemic chemotherapy for mCRPC (previous treatment with six
cycles of docetaxel for metastatic castration-sensitive prostate cancer (mCSPC) is
permissible). NOTE: patients receiving fewer than 2 cycles of taxane based regimen due
to intolerance are eligible for cohort 1.

7. For inclusion in Cohort 2, mCRPC patients must have progressed while receiving (or
subsequent to receiving) abiraterone and/or enzalutamide and must have progressed
subsequent to receiving ≥ 2 cycles of a taxane-based regimen for mCRPC.

8. Patients must have a ECOG performance status of 0 or 1

9. Patients must have at least one metastatic lesion that can be followed on baseline
imaging obtained no more than 28 days prior to beginning study therapy. Baseline and
follow up radiological disease assessments must include bone scans performed with
99mTc labelled diphosphonates

10. Patients with a history of CNS metastases must have received therapy (surgery,
radiotherapy, gamma knife) and be neurologically stable, asymptomatic, and not
receiving corticosteroids for the purposes of maintaining neurologic integrity.
Patients with epidural disease, canal disease and prior cord involvement are eligible
if those areas have been treated, are stable, and not neurologically impaired. For
patients with parenchymal CNS metastasis (or a history of CNS metastasis), baseline
and subsequent radiological imaging must include evaluation of the brain (MRI
preferred or CT with contrast)

11. Patients must have recovered (to baseline/stabilization) from prior chemo- or
radio-therapy and associated acute toxicities must have resolved to a NCI CTCAE v4
Grade 1 or less, with the exception of alopecia

12. Patients must have adequate organ function:

a) Bone marrow reserve: ANC ≥ 1.5 x 109/L, platelets ≥ 100 x 109/L, hemoglobin ≥ 9
g/dL b) Cardiac: i) QTcF < 450 msec on at least 2 of 3 screening ECGs. On site
determination of QTcF may be used for screening purposes ii) LVEF equal to or greater
than the institutional lower limit of normal. LVEF must be evaluated within 7 to 10
days prior to beginning study therapy iii) Cardiac Troponin I within normal limit (as
per local institution) c) Hepatic: Total bilirubin ≤ 1.5 x ULN, ALT, AST ≤ 3.0 x ULN
OR ≤ 5.0 x ULN for patients with liver metastases d) Renal: Serum/plasma creatinine ≤
1.5 x ULN, or for patients with serum/plasma creatinine > 1.5 ULN, creatinine
clearance ≥ 50 mL/min

Exclusion Criteria for Part B:

The presence of any of the following will exclude the patient from the study:

1. Previous treatment with Samarium-153, Strontium-89, Rhenium-186 or Radium-223 within 6
months of starting (i.e., Cycle 1 Day 1) EC1169

2. Any systemic anti-cancer therapy (e.g., chemotherapy, immunotherapy or biological
therapy (including monoclonal antibodies), or experimental anti-cancer therapy) within
28 days prior to beginning study therapy. Note: Ongoing castrating therapy with a GnRH
agonist or antagonist is mandatory to assure a castrate level of serum testosterone
<50 ng/dL, except in patients who have undergone an orchiectomy. Bisphosphonates or
denosumab continuation is permissible (i.e., no change for 30 days prior to Cycle 1
Day 1). Patients who receive a dose of EC1169 under another Endocyte protocol do not
need a washout period for EC1169

3. Known hypersensitivity to the components of the study therapy. (Please reference
Section 1, Formulation of EC1169 and EC0652, in the respective Pharmacy Manuals)

4. Carcinomatous meningitis and/or symptomatic CNS metastases

5. Concurrent malignancies that are expected to alter life expectancy (e.g., NSCLC, etc.)
or that may interfere with assessment of prostate cancer (e.g., lymphoma involving the
periaortic nodes). Patients with adequately treated non-melanoma skin cancer or
non-muscle invasive urothelial carcinoma, and patients with prior history of
malignancy who have been disease-free for more than 5 years are eligible

6. Patients considered at risk for life-threatening QTc prolongation (i.e., personal or
family history of Long QT syndrome, presence of implantable pacemaker, or implantable
cardioverter defibrillator, etc.)

7. Use of the following medications within 6 months prior to EC1169 administration:
amiodarone, disopyramide, dofetilide, dronedarone, flecanamide, ibutilide, quinidine,
or sotalol

8. Any other serious cardiac illness or medical conditions such as unstable angina,
pulmonary embolism, or uncontrolled hypertension

9. Known systemic infections including, but not limited to hepatitis B or C, or HIV