Study of HPN424 in Patients With Advanced Prostate Cancer

NCT ID: NCT03577028

Last Updated: 2024-02-14

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 104 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-07-24
• Study Completion Date: 2023-02-27

Brief Summary

An open-label, Phase 1/2a, study of HPN424 as monotherapy to assess the safety, tolerability and PK in patients with advanced prostate cancer refractory to androgen therapy

Conditions

Advanced Prostate Cancer

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Fixed IV

HPN424 administered once weekly via IV infusion in doses ranging from 1.3 to 150 ng/kg

Group Type: EXPERIMENTAL

HPN424 Fixed IV 1.3 to 150 ng/kg

Intervention Type: BIOLOGICAL

Fixed dose IV cohorts at doses from 1.3 to 150 ng/kg

1 Prime Step IV 36 ng/kg Target

Step-dosing IV cohort who received a single Prime Dose followed by the Target Dose (12/36 ng/kg)

Group Type: EXPERIMENTAL

HPN424 Prime Step IV 36 ng/kg Target

Intervention Type: BIOLOGICAL

Step-dosing IV cohort at a single Prime Dose followed by the Target Dose (12/36 ng/kg)

1 Prime Step IV 225-300 ng/kg Target

Step-dosing IV cohorts who received a single Prime Dose followed by the Target Dose (100/300 ng/kg and 75/225 ng/kg\]

Group Type: EXPERIMENTAL

HPN424 1 Prime Step IV 225-300 ng/kg Target

Intervention Type: BIOLOGICAL

Step-dosing IV cohorts who received a single Prime Dose followed by the Target Dose (100/300 ng/kg and 75/225 ng/kg)

2 Prime Step IV 300 ng/kg Target

Step-dosing IV cohorts who received 2 Prime Doses followed by the Target Dose (50/150/300 ng/kg with prior chemotherapy and 50/150/300 ng/kg no prior chemotherapy)

Group Type: EXPERIMENTAL

HPN424 2 Prime Step IV 300 ng/kg Target

Intervention Type: BIOLOGICAL

Step-dosing IV cohorts who received 2 Prime Doses followed by the Target Dose (50/150/300 ng/kg with prior chemotherapy and 50/150/300 ng/kg no prior chemotherapy)

2 Prime Step IV 450 ng/kg Target

Step-dosing IV cohorts who received 2 Prime Doses followed by the Target Dose (100/300/450 ng/kg and 50/150/450 ng/kg)

Group Type: EXPERIMENTAL

HPN424 2 Prime Step IV 450 ng/kg Target

Intervention Type: BIOLOGICAL

Step-dosing IV cohorts who received 2 Prime Doses followed by the Target Dose (100/300/450 ng/kg and 50/150/450 ng/kg)

Fixed SC

Fixed subcutaneous dose (120 ng/kg)

Group Type: EXPERIMENTAL

HPN424 Fixed SC

Intervention Type: BIOLOGICAL

Fixed subcutaneous dose 120 ng/kg

Interventions

HPN424 Fixed IV 1.3 to 150 ng/kg

Fixed dose IV cohorts at doses from 1.3 to 150 ng/kg

Intervention Type: BIOLOGICAL

HPN424 Prime Step IV 36 ng/kg Target

Step-dosing IV cohort at a single Prime Dose followed by the Target Dose (12/36 ng/kg)

Intervention Type: BIOLOGICAL

HPN424 1 Prime Step IV 225-300 ng/kg Target

Step-dosing IV cohorts who received a single Prime Dose followed by the Target Dose (100/300 ng/kg and 75/225 ng/kg)

Intervention Type: BIOLOGICAL

HPN424 2 Prime Step IV 300 ng/kg Target

Step-dosing IV cohorts who received 2 Prime Doses followed by the Target Dose (50/150/300 ng/kg with prior chemotherapy and 50/150/300 ng/kg no prior chemotherapy)

Intervention Type: BIOLOGICAL

HPN424 2 Prime Step IV 450 ng/kg Target

Step-dosing IV cohorts who received 2 Prime Doses followed by the Target Dose (100/300/450 ng/kg and 50/150/450 ng/kg)

Intervention Type: BIOLOGICAL

HPN424 Fixed SC

Fixed subcutaneous dose 120 ng/kg

Intervention Type: BIOLOGICAL

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: No

Sponsors

Harpoon Therapeutics, Inc., a subsidiary of Merck & Co., Inc. (Rahway, New Jersey USA)

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

USC Norris Comprehensive Cancer Center

Los Angeles, California, United States

University of California San Francisco

San Francisco, California, United States

University of Colorado Hospital

Aurora, Colorado, United States

Northwestern University

Chicago, Illinois, United States

University of Chicago

Chicago, Illinois, United States

Massachusetts General Hospital

Boston, Massachusetts, United States

Karmanos Cancer Institute

Detroit, Michigan, United States

New York Presbyterian Hospital-Columbia University Medical Center.

New York, New York, United States

Oregon Health & Science University Knight Cancer Institute

Portland, Oregon, United States

Fox Chase Cancer Center

Philadelphia, Pennsylvania, United States

Sarah Cannon Research Institute

Nashville, Tennessee, United States

Mary Crowley Cancer Research

Dallas, Texas, United States

UT Southwestern Medical Center

Dallas, Texas, United States

University of Wisconsin Carbone Cancer Center

Madison, Wisconsin, United States

The Royal Marsden Hospital

Sutton, Surrey, United Kingdom

Countries

United States; United Kingdom

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

HPN424-1001

Identifier Type: -

Identifier Source: org_study_id