| Eligibility |
Inclusion Criteria:
1. Male patients =18 years of age at the time of signing informed consent
2. Histologically or cytologically confirmed adenocarcinoma of the prostate
3. Progressive metastatic castrate-resistant prostate cancer (mCRPC):
1. Serum testosterone levels less than 50 ng/dL (or =0.50 ng/mL or 1.73 nmol/L)
within 28 days prior to start of study drug
2. Radiographic evidence of metastatic disease
3. Disease progression on the prior systemic regimen, per Prostate Cancer Clinical
Trials Working Group 3 (PCWG3) criteria:
i. A sequence of at least 2 rising PSA values measured at a minimum of 1 week apart
with a 2 ng/mL minimum starting value, or ii. Appearance of two or more new lesions on
bone scans, or iii. Progressive visceral disease, or iv. Progressive nodal disease;
previously normal (<1.0 cm) lymph nodes must have grown by =5 mm in the short axis
from baseline or nadir and be =1.0 cm in the short axis to be considered to have
progressed
4. Must have received at least 2 prior systemic therapies approved for mCRPC
5. Ongoing androgen depletion therapy with a gonadotropin releasing hormone analog or
inhibitor, or orchiectomy (surgical or medical castration)
6. For patients previously treated with first generation anti-androgens, discontinuation
must have occurred =4 weeks (for flutamide or nilutamide) or =6 weeks (for
bicalutamide) prior to start of study drug, with no evidence of an anti-androgen
withdrawal response (i.e., no decline in serum PSA)
7. For patients previously treated with a second-generation anti-androgen (e.g.,
enzalutamide or equivalent) or with abiraterone acetate, discontinuation must have
occurred 2 weeks or 5 half-lives prior to start of study drug
8. For patients previously treated with systemic chemotherapy, targeted therapy,
immunotherapy, or treatment with an investigational anticancer agent, discontinuation
must have occurred =2 weeks, or at least 4 half-lives (up to 4 weeks), whichever is
longer, prior to start of study drug
9. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
10. Adequate bone marrow function, including:
1. Absolute neutrophil count (ANC) =1500/mm3 or =1.5 x 109/L
2. Platelets =100,000/mm3 or =100 x 109/L
3. Hemoglobin =9 g/dL (no transfusions allowed within 1 week prior to screening)
11. Adequate renal function, including:
a. Estimated creatinine clearance =50 mL/min as calculated using the method standard
for the institution
12. Adequate liver function, including:
1. Total serum bilirubin =1.5 x upper limit of normal (ULN) unless the patient has
documented Gilbert syndrome in which case the maximum total serum bilirubin
should be 5 mg/dL
2. Aspartate and Alanine transaminase (AST and ALT) =2.5 x ULN
13. Resolved acute effects of any prior therapy to baseline severity or CTCAE Grade =1
except for adverse events (AEs) not constituting a safety risk per the Investigator
14. If of reproductive potential, willing to use 1 effective method of contraception (as
defined in this protocol) during the treatment period, if partner is a female of
childbearing potential
15. Willing to complete all scheduled visits and assessments at the institution
administering therapy
16. Able to read, understand and provide written informed consent
Exclusion Criteria:
1. Previously treated or current brain metastases
2. Untreated spinal cord compression. Participants must be neurologically stable off
steroids for at least 4 weeks prior to first dose of study drug
3. Ongoing treatment with anti-tumor necrosis factor (TNF) alpha therapies, systemic
corticosteroids (prednisone dose >10 mg per day or equivalent), or other immune
suppressive drugs
4. History of or known or suspected autoimmune disease (exception(s): patients with
vitiligo, resolved childhood atopic dermatitis, hypothyroidism, or hyperthyroidism
that is clinically euthyroid at Screening are allowed)
5. History of clinically significant cardiovascular disease such as symptomatic
congestive heart failure (CHF), uncontrolled hypertension defined as sustained BP >150
mmHg systolic, or >100 mmHg diastolic despite optimal antihypertensive treatment (BP
must be controlled at screening), unstable angina pectoris, clinically significant
cardiac arrhythmias, history of stroke (including TIA, or other ischemic event) within
6 months before first dose of study drug, myocardial infarction within 6 months before
first dose of study drug, history of thromboembolic event within 3 months before first
dose of study drug
6. Known active or chronic hepatitis B or hepatitis C as demonstrated by hepatitis B
surface antigen (HBsAg) positivity and/or anti-hepatitis C virus (HCV) positivity,
respectively, or known history of human immunodeficiency virus (HIV) seropositive
status
7. Clinically active liver disease, including liver cirrhosis of Child-Pugh class B or C
8. Second primary malignancy that has not been in remission for greater than 3 years.
Exceptions that do not require a 3-year remission: non-melanoma skin cancer, resected
melanoma in situ, or non-muscle invasive urothelial carcinoma
9. In the judgment of the Investigator, patient has a clinically significant concurrent
illness or psychological, familial, sociological, geographical, or other concomitant
condition that would not permit adequate follow-up and compliance with the study
protocol
10. Any serious underlying medical or psychiatric condition (e.g., alcohol or drug abuse),
dementia or altered mental status or any issue that would impair the ability of the
patient to understand informed consent or that in the opinion of the Investigator
would contraindicate the patient's participation in the study or confound the results
of the study
11. Known hypersensitivity, allergies, or intolerance to immunoglobulins, or to any
excipient contained in HPN424 (see Investigator's Brochure)
12. Is a participant or plans to participate in another interventional clinical study,
while taking part in this protocol. Participation in an observational study is
acceptable
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