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Study of HPN424 in Patients With Advanced Prostate Cancer

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT03577028
Recruitment Status : Active, not recruiting
First Posted : July 5, 2018
Last Update Posted : January 25, 2023
Information provided by (Responsible Party):
Harpoon Therapeutics

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

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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

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Prostate Cancer

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.

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.

Information from the National Library of Medicine

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

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03577028

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

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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
Additional relevant MeSH terms:
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Prostatic Neoplasms
Genital Neoplasms, Male
Urogenital Neoplasms
Neoplasms by Site
Genital Diseases, Male
Genital Diseases
Urogenital Diseases
Prostatic Diseases
Male Urogenital Diseases