Study of HPN536 in Patients With Advanced Cancers Associated With Mesothelin Expression
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
1 other identifier
interventional
95
1 country
16
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.(Phase 2 portion of the study was not conducted.)
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_1
Started Apr 2019
Typical duration for phase_1
16 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
March 11, 2019
CompletedFirst Posted
Study publicly available on registry
March 13, 2019
CompletedStudy Start
First participant enrolled
April 16, 2019
CompletedPrimary Completion
Last participant's last visit for primary outcome
January 4, 2023
CompletedStudy Completion
Last participant's last visit for all outcomes
January 4, 2023
CompletedJune 7, 2024
June 1, 2024
3.7 years
March 11, 2019
June 5, 2024
Conditions
Outcome Measures
Primary Outcomes (3)
Assessment of Adverse Events by CTCAE 5.0 of HPN536
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)
3 years
Determine MTD/RP2D
Estimate the maximum tolerated dose (MTD) or select the recommended Phase 2 dose (RP2D)
2 years
Efficacy of HPN536 at the recommended Phase 2 dose: overall response rate (ORR)
Evaluate overall response rate (ORR) as assessed by RECIST
1 year
Study Arms (3)
Fixed IV
EXPERIMENTALHPN536 administered once weekly via IV infusion in doses ranging from 6 to 560 ng/kg
1 Prime Step IV 600-1200 ng/kg Target
EXPERIMENTALStep-dosing IV cohorts who received a single Prime Dose followed by the Target Dose (200/600 ng/kg, 200/1200 ng/kg, and 500/900 ng/kg)
2 Prime Step IV 900-14000 ng/kg Target
EXPERIMENTALStep-dosing IV cohorts who received 2 Prime Doses followed by the Target Dose (200/600/900 ng/kg and 200/600/1200 ng/kg; 500/900/1200 ng/kg, 500/900/1800 ng/kg, 500/900/3600 ng/kg, 500/900/7200 ng/kg, and 500/900/14400 ng/kg)
Interventions
Step-dosing IV cohorts who received a single Prime Dose followed by the Target Dose (200/600 ng/kg, 200/1200 ng/kg, and 500/900 ng/kg)
Step-dosing IV cohorts who received 2 Prime Doses followed by the Target Dose (200/600/900 ng/kg and 200/600/1200 ng/kg; 500/900/1200 ng/kg, 500/900/1800 ng/kg, 500/900/3600 ng/kg, 500/900/7200 ng/kg, and 500/900/14400 ng/kg)
Eligibility Criteria
You may not qualify if:
- 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
- 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 based on computed tomography (CT), magnetic resonance imaging (MRI), or echocardiogram (ECHO); or prior history of pleurodesis, retroperitoneal fibrosis or mediastinal fibrosis.
- Previous Grade 3/4 infusion or hypersensitivity reaction (not immunotoxicity) to treatment with another monoclonal antibody.
- 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.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (16)
Mayo Clinic Arizona
Phoenix, Arizona, 85054, United States
University of Southern California
Los Angeles, California, 90007, United States
University of California Los Angeles
Los Angeles, California, 90095-7170, United States
Mayo Clinic Florida
Jacksonville, Florida, 32224, United States
University of Chicago
Chicago, Illinois, 60637, United States
Massachusetts General Hospital
Boston, Massachusetts, 02114, United States
Mayo Clinic Rochester
Rochester, Minnesota, 55905, United States
Washington University School of Medicine in St. Louis
St Louis, Missouri, 63110, United States
Memorial Sloan Kettering Cancer Center
New York, New York, 10017, United States
Cleveland Clinic Taussig Cancer Institute
Cleveland, Ohio, 44195, United States
Stephenson Cancer Center
Oklahoma City, Oklahoma, 73104, United States
Thomas Jefferson University
Philadelphia, Pennsylvania, 19107, United States
Sarah Cannon Research Institute
Nashville, Tennessee, 37203, United States
Mary Crowley Cancer Research
Dallas, Texas, 75230, United States
University of Virginia Cancer Center
Charlottesville, Virginia, 22903, United States
University of Washington Medical Center
Seattle, Washington, 98195, United States
Related Publications (1)
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.
PMID: 33262134DERIVED
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
March 11, 2019
First Posted
March 13, 2019
Study Start
April 16, 2019
Primary Completion
January 4, 2023
Study Completion
January 4, 2023
Last Updated
June 7, 2024
Record last verified: 2024-06