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

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

Study Description

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

Study Design

• 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

Arms and Interventions

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

Outcome Measures

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

Eligibility Criteria

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

Criteria

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.

Contacts and Locations

Locations

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

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Molloy ME, Austin RJ, Lemon BD, Aaron WH, Ganti V, Jones A, Jones SD, Strobel KL, Patnaik P, Sexton K, Tatalick L, Yu TZ, Baeuerle PA, Law CL, Wesche H. Preclinical Characterization of HPN536, a Trispecific, T-Cell-Activating Protein Construct for the Treatment of Mesothelin-Expressing Solid Tumors. Clin Cancer Res. 2021 Mar 1;27(5):1452-1462. doi: 10.1158/1078-0432.CCR-20-3392. Epub 2020 Dec 1.

• Responsible Party: Harpoon Therapeutics
• ClinicalTrials.gov Identifier: NCT03872206
• Other Study ID Numbers: HPN536-2001
• First Posted: March 13, 2019
• Last Update Posted: September 13, 2022
• Last Verified: September 2022

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

Additional relevant MeSH terms:

Neoplasms