Study of HPN424 in Patients With Advanced Prostate Cancer

NCT03577028 | Terminated Phase 1 Results FDA Drug

• 1 other identifier: HPN424-1001
• Study Type: interventional
• Target: 104
• Locations: 2 countries
• Sites: 15

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

Keywords

Prostate Cancer; Metastatic Castration Resistant Prostate Cancer; Harpoon; TriTAC

Outcome Measures

Primary Outcomes (1)

• Number and Severity of Dose Limiting Toxicities (DLTs) Following Treatment With Escalating Doses of HPN424

  Assess safety and tolerability at increasing dose levels of HPN424 in successive cohorts of patients with metastatic castrate resistant prostate cancer (mCRPC) to estimate the maximum tolerated dose (MTD). The study was terminated early, therefore the primary goal of the final data analysis was to look at dosing schedule rather than individual dose levels. The results displayed are shown broken out by dosing schedules and no analysis of specific dose levels was performed. This analysis is as outlined in the final Statistical Analysis Plan.

  21 days

Study Arms (6)

Fixed IV

EXPERIMENTAL

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

Biological: HPN424 Fixed IV 1.3 to 150 ng/kg

1 Prime Step IV 36 ng/kg Target

EXPERIMENTAL

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

Biological: HPN424 Prime Step IV 36 ng/kg Target

1 Prime Step IV 225-300 ng/kg Target

EXPERIMENTAL

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

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

2 Prime Step IV 300 ng/kg Target

EXPERIMENTAL

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)

Biological: HPN424 2 Prime Step IV 300 ng/kg Target

2 Prime Step IV 450 ng/kg Target

EXPERIMENTAL

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)

Biological: HPN424 2 Prime Step IV 450 ng/kg Target

Fixed SC

EXPERIMENTAL

Fixed subcutaneous dose (120 ng/kg)

Biological: HPN424 Fixed SC

Interventions

HPN424 Fixed IV 1.3 to 150 ng/kg BIOLOGICAL

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

Fixed IV

HPN424 Prime Step IV 36 ng/kg Target BIOLOGICAL

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

1 Prime Step IV 36 ng/kg Target

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

1 Prime Step IV 225-300 ng/kg Target

HPN424 2 Prime Step IV 300 ng/kg Target 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 300 ng/kg Target

HPN424 2 Prime Step IV 450 ng/kg Target 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)

2 Prime Step IV 450 ng/kg Target

HPN424 Fixed SC BIOLOGICAL

Fixed subcutaneous dose 120 ng/kg

Fixed SC

Eligibility Criteria

• Age: 18 Years+
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male patients ≥18 years of age at the time of signing informed consent
• Histologically or cytologically confirmed adenocarcinoma of the prostate
• Progressive metastatic castrate-resistant prostate cancer (mCRPC):
• 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
• Radiographic evidence of metastatic disease
• 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
• Must have received at least 2 prior systemic therapies approved for mCRPC
• Ongoing androgen depletion therapy with a gonadotropin releasing hormone analog or inhibitor, or orchiectomy (surgical or medical castration)
• 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)
• 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
• 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
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
• Adequate bone marrow function, including:
• Absolute neutrophil count (ANC) ≥1500/mm3 or ≥1.5 x 109/L

You may not qualify if:

• Previously treated or current brain metastases
• Untreated spinal cord compression. Participants must be neurologically stable off steroids for at least 4 weeks prior to first dose of study drug
• 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
• 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)
• 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
• 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
• Clinically active liver disease, including liver cirrhosis of Child-Pugh class B or C
• 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
• 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
• 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
• Known hypersensitivity, allergies, or intolerance to immunoglobulins, or to any excipient contained in HPN424 (see Investigator's Brochure)
• 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

Sponsors & Collaborators

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

Study Sites (15)

USC Norris Comprehensive Cancer Center

Los Angeles, California, 90033, United States

Location

University of California San Francisco

San Francisco, California, 94143, United States

Location

University of Colorado Hospital

Aurora, Colorado, 80045, United States

Location

Northwestern University

Chicago, Illinois, 60611, United States

Location

University of Chicago

Chicago, Illinois, 60637, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Karmanos Cancer Institute

Detroit, Michigan, 48201, United States

Location

New York Presbyterian Hospital-Columbia University Medical Center.

New York, New York, 10032, United States

Location

Oregon Health & Science University Knight Cancer Institute

Portland, Oregon, 97239, United States

Location

Fox Chase Cancer Center

Philadelphia, Pennsylvania, 19111-2497, United States

Location

Sarah Cannon Research Institute

Nashville, Tennessee, 37203, United States

Location

Mary Crowley Cancer Research

Dallas, Texas, 75230, United States

Location

UT Southwestern Medical Center

Dallas, Texas, 75390, United States

Location

University of Wisconsin Carbone Cancer Center

Madison, Wisconsin, 53972, United States

Location

The Royal Marsden Hospital

Sutton, Surrey, SM2 5PT, United Kingdom

Location

MeSH Terms

Conditions

Prostatic Neoplasms

Condition Hierarchy (Ancestors)

Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases

Results Point of Contact

• Title: Medical Director
• Organization: Harpoon Therapeutics

HPN4241001@harpoontx.com

1-650-452-728

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 22, 2018
• First Posted: July 5, 2018
• Study Start: July 24, 2018
• Primary Completion: February 27, 2023
• Study Completion: February 27, 2023
• Last Updated: February 14, 2024
• Results First Posted: February 14, 2024

Record last verified: 2024-01

Locations

GB (1); US (14)