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Study of HPN536 in Patients With Advanced Cancers Associated With Mesothelin Expression

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: NCT03872206
Recruitment Status : Active, not recruiting
First Posted : March 13, 2019
Last Update Posted : September 13, 2022
Information provided by (Responsible Party):
Harpoon Therapeutics

Brief Summary:
An open-label, Phase 1/2a study of HPN536 as monotherapy to assess the safety, tolerability and PK in patients with advanced cancers associated with mesothelin expression.

Condition or disease Intervention/treatment Phase
Advanced Cancers Associated With Mesothelin Expression Biological: HPN536 Phase 1 Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 200 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 HPN536 in Patients With Advanced Cancers Associated With Mesothelin Expression Who Have Failed Standard Available Therapy
Actual Study Start Date : April 16, 2019
Estimated Primary Completion Date : February 1, 2023
Estimated Study Completion Date : May 1, 2023

Arm Intervention/treatment
Experimental: HPN536-2001 - Part 1 (Dose Escalation)
HPN536 is IV administered once weekly for about 1 hour. Doses will vary between cohorts as MTD is being determined.
Biological: HPN536
Dose escalation: HPN536 is a tri-specific recombinant protein construct (Tri-specific T Cell Activating Construct [TriTAC®]) containing 3 humanized antibody derived binding domains

Experimental: HPN536-2001 - Part 2 (Dose Expansion)
HPN536 is IV administered once weekly for about 1 hour at the recommended phase 2 dose established in Part 1
Biological: HPN536
Dose expansion: HPN536 is a tri-specific recombinant protein construct (Tri-specific T Cell Activating Construct [TriTAC®]) containing 3 humanized antibody derived binding domains

Primary Outcome Measures :
  1. Assessment of Adverse Events by CTCAE 5.0 of HPN536 [ Time Frame: 3 years ]
    Assess safety and tolerability at increasing dose levels of HPN536 in successive cohorts of patients with of patients with epithelial ovarian cancer, fallopian tube cancer, primary peritoneal cancer, pancreatic adenocarcinoma, or mesothelioma (pleural and primary peritoneal) by adverse events (CTCAE v5.0)

  2. Determine MTD/RP2D [ Time Frame: 2 years ]
    Estimate the maximum tolerated dose (MTD) or select the recommended Phase 2 dose (RP2D)

  3. Efficacy of HPN536 at the recommended Phase 2 dose: overall response rate (ORR) [ Time Frame: 1 year ]
    Evaluate overall response rate (ORR) as assessed by RECIST

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:   All
Accepts Healthy Volunteers:   No
  1. One of the following progressive advanced or metastatic cancers:

    1. Epithelial ovarian, fallopian tube, or primary peritoneal cancer that is platinum refractory or platinum resistant
    2. Pancreatic adenocarcinoma that is locally advanced, and now with progressive disease on or after front-line treatment
    3. Malignant mesothelioma with epithelioid histology, pleural or peritoneal
  2. For Part 2 only - Measurable disease according to RECIST v1.1 for patients with epithelial ovarian, fallopian tube, or primary peritoneal cancer, pancreatic adenocarcinoma, and peritoneal mesothelioma, and mRECIST v1.1 for patients with pleural mesothelioma
  3. Available archival tissue sample, or fresh biopsy tissue sample must be obtained prior to enrollment. For Part 2 only- a fresh biopsy tissue sample is required.
  4. 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 (Hgb) ≥9 g/dL
  5. Adequate renal function, including estimated creatinine clearance ≥30 mL/min
  6. 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 or AST/ALT ≤5 x ULN for patients with liver metastases
  7. Serum albumin ≥30 mg/mL

Key Exclusion Criteria:

  1. Brain metastases unless previously treated. Patients with previously treated brain metastases may participate provided they are clinically stable for at least 4 weeks prior to study entry, and have no evidence of new or enlarging brain metastases
  2. Evidence of retroperitoneal fibrosis, mesothelial surface (pleura, pericardium, peritoneum) thickening of ≥4 mm; significant or increasing pleural/pericardial effusions, ascites or pericarditis at baseline deemed unrelated to the underlying malignancy basedon computed tomography (CT), magnetic resonance imaging (MRI), or echocardiogram (ECHO); or prior history of pleurodesis, retroperitoneal fibrosis or mediastinal fibrosis.
  3. Previous Grade 3/4 infusion or hypersensitivity reaction (not immunotoxicity) to treatment with another monoclonal antibody.
  4. For patients with tumor types other than pleural mesothelioma: Ascites requiring >1 paracentesis for therapeutic purposes (i.e., not for diagnosis) within 1 month prior to Cycle 1 Day 1.

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): NCT03872206

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United States, Arizona
Mayo Clinic Arizona
Phoenix, Arizona, United States, 85054
United States, California
University of Southern California
Los Angeles, California, United States, 90007
University of California Los Angeles
Los Angeles, California, United States, 90095-7170
United States, Florida
Mayo Clinic Florida
Jacksonville, Florida, United States, 32224
United States, Illinois
University of Chicago
Chicago, Illinois, United States, 60637
United States, Massachusetts
Massachusetts General Hospital
Boston, Massachusetts, United States, 02114
United States, Minnesota
Mayo Clinic Rochester
Rochester, Minnesota, United States, 55905
United States, Missouri
Washington University School of Medicine in St. Louis
Saint Louis, Missouri, United States, 63110
United States, New York
Memorial Sloan Kettering Cancer Center
New York, New York, United States, 10017
United States, Ohio
Cleveland Clinic Taussig Cancer Institute
Cleveland, Ohio, United States, 44195
United States, Oklahoma
Stephenson Cancer Center
Oklahoma City, Oklahoma, United States, 73104
United States, Pennsylvania
Thomas Jefferson University
Philadelphia, Pennsylvania, United States, 19107
United States, Tennessee
Sarah Cannon Research Institute
Nashville, Tennessee, United States, 37203
United States, Texas
Mary Crowley Cancer Research
Dallas, Texas, United States, 75230
United States, Virginia
University of Virginia Cancer Center
Charlottesville, Virginia, United States, 22903
United States, Washington
University of Washington Medical Center
Seattle, Washington, United States, 98195
Sponsors and Collaborators
Harpoon Therapeutics
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Harpoon Therapeutics
ClinicalTrials.gov Identifier: NCT03872206    
Other Study ID Numbers: HPN536-2001
First Posted: March 13, 2019    Key Record Dates
Last Update Posted: September 13, 2022
Last Verified: September 2022

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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