Study of HPN424 in Patients With Advanced Prostate Cancer

• ClinicalTrials.gov Identifier: NCT03577028
• Recruitment Status: Active, not recruiting
• First Posted: July 5, 2018
• Last Update Posted: January 25, 2023
• Sponsor: Harpoon Therapeutics
• Information provided by (Responsible Party): Harpoon Therapeutics

Study Description

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

Condition or disease	Intervention/treatment	Phase
Advanced Prostate Cancer	Biological: HPN424 In Part 1 (Dose Escalation); Biological: HPN424 In Part 2 (Dose Expansion)	Phase 1; Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 110 participants
• Allocation: Non-Randomized
• Intervention Model: Sequential Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase 1/2a Open-label, Multicenter, Dose Escalation and Dose Expansion Study of the Safety, Tolerability, and Pharmacokinetics of HPN424 in Patients With Advanced Prostate Cancer Refractory to Androgen Therapy
• Actual Study Start Date: July 24, 2018
• Estimated Primary Completion Date: March 2023
• Estimated Study Completion Date: March 2023

Arms and Interventions

Arm	Intervention/treatment
Experimental: Part 1 (Dose Escalation); HPN424 will be administered once weekly via IV infusion or subcutaneously with dose escalation until an estimated therapeutic dose level has been reached.	Biological: HPN424 In Part 1 (Dose Escalation); HPN424 will be administered once weekly via IV infusion or subcutaneously.
Experimental: Part 2 (Dose Expansion); Patients will receive HPN424 at the recommended phase 2 dose(s) established in Part 1 of the study. Study procedures will be the same in Part 1 and Part 2 of the study. Additional expansion cohorts of up to 18 patients per expansion cohort may be added.	Biological: HPN424 In Part 2 (Dose Expansion); HPN424 will be administered at the recommended phase 2 dose(s) once weekly via IV infusion or subcutaneously.

Outcome Measures

Primary Outcome Measures :

1. Part 1: Number and severity of dose limiting toxicities (DLTs) of HPN424 [ Time Frame: Baseline through end of Cycle 2 (each cycle is 21 days) ]
   Assess safety and tolerability at increasing dose levels of HPN424 in successive cohorts of patients with metastatic castrate resistant prostate cancer (mCRPC) to select the recommended Phase 2 dose(s) (RP2D), and dosing regimen for further investigation by measuring incidence of DLTs.
2. Part 2: Overall response rate (ORR) as assessed by PCWG3 criteria for response [ Time Frame: up to 4 years ]
   Evaluate preliminary clinical efficacy of HPN424 at recommended phase 2 dose (RP2D) by determining ORR as measured by bone scans, CT/MRI and prostate specific antigen (PSA) levels.

Secondary Outcome Measures :

1. Part 1 and 2: Adverse events (NCI CTCAE version 5.0) [ Time Frame: up to 4 years ]
   Evaluate the overall safety profile of HPN424 administered by IV infusion or SC injection, as measured by adverse events.
2. Part 1: Progression-free survival (PFS) using PCWG3 criteria [ Time Frame: up to 4 years ]
   Evaluate preliminary clinical anti-tumor activity by measuring PFS.
3. Part 1: Duration of response (DOR) using PCWG3 criteria [ Time Frame: up to 4 years ]
   Evaluate preliminary clinical anti-tumor activity by measuring DOR.
4. Part 1: Overall survival (OS) [ Time Frame: up to 4 years ]
   Evaluate preliminary clinical anti-tumor activity by measuring OS.
5. Part 1: Prostate Specific Antigen (PSA) levels [ Time Frame: up to 4 years ]
   Evaluate preliminary clinical anti-tumor activity by measuring PSA levels in blood.
6. Part 1 and 2: Pharmacokinetics of HPN424 [ Time Frame: up to 4 years ]
   Characterize single dose and multiple dose PK of HPN424 following IV administration by measuring levels of HPN424 in blood serum.
7. Part 1 and 2: Incidence of anti-drug antibodies (ADA) against HPN424 [ Time Frame: up to 4 years ]
   Evaluate the immunogenicity of HPN424 by assessing anti-drug antibodies in blood serum.
8. Part 1 and 2: Effects of HPN424 on circulating lymphocytes and systemic soluble immune factors [ Time Frame: up to 4 years ]
   Characterize the impact of HPN424 on activation of circulating lymphocytes and on systemic soluble immune factors by immunophenotyping of lymphocytes in whole blood and measuring cytokines in serum.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: Male
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

United States, California

USC Norris Comprehensive Cancer Center

Los Angeles, California, United States, 90033

University of California San Francisco

San Francisco, California, United States, 94143

United States, Colorado

University of Colorado Hospital

Aurora, Colorado, United States, 80045

United States, Illinois

Northwestern University

Chicago, Illinois, United States, 60611

University of Chicago

Chicago, Illinois, United States, 60637

United States, Massachusetts

Massachusetts General Hospital

Boston, Massachusetts, United States, 02114

United States, Michigan

Karmanos Cancer Institute

Detroit, Michigan, United States, 48201

United States, New York

New York Presbyterian Hospital-Columbia University Medical Center.

New York, New York, United States, 10032

United States, Oregon

Oregon Health & Science University Knight Cancer Institute

Portland, Oregon, United States, 97239

United States, Pennsylvania

Fox Chase Cancer Center

Philadelphia, Pennsylvania, United States, 19111-2497

United States, Tennessee

Sarah Cannon Research Institute

Nashville, Tennessee, United States, 37203

United States, Texas

Mary Crowley Cancer Research

Dallas, Texas, United States, 75230

UT Southwestern Medical Center

Dallas, Texas, United States, 75390

United States, Wisconsin

University of Wisconsin Carbone Cancer Center

Madison, Wisconsin, United States, 53972

United Kingdom

The Royal Marsden Hospital

Sutton, Surrey, United Kingdom, SM2 5PT

Sponsors and Collaborators

Harpoon Therapeutics

More Information

• Responsible Party: Harpoon Therapeutics
• ClinicalTrials.gov Identifier: NCT03577028
• Other Study ID Numbers: HPN424-1001
• First Posted: July 5, 2018
• Last Update Posted: January 25, 2023
• Last Verified: January 2023

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Harpoon Therapeutics:

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

Additional relevant MeSH terms:

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