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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. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03872206
Recruitment Status : Recruiting
First Posted : March 13, 2019
Last Update Posted : April 15, 2021
Sponsor:
Information provided by (Responsible Party):
Harpoon Therapeutics

Tracking Information
First Submitted Date  ICMJE March 11, 2019
First Posted Date  ICMJE March 13, 2019
Last Update Posted Date April 15, 2021
Actual Study Start Date  ICMJE April 16, 2019
Estimated Primary Completion Date April 1, 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: April 12, 2021)
  • Assess initial safety and determination of recommended Phase 2 dose: Dose limiting toxicity [ Time Frame: Up to study day 21 ]
    Dose limiting toxicity measured by adverse events and serious adverse events will be reviewed by dose level by the Safety Oversight Committee and will result in a recommended Phase 2 dose.
  • 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
Original Primary Outcome Measures  ICMJE
 (submitted: March 12, 2019)
  • Assess initial safety and determination of recommended Phase 2 dose: Dose limiting toxicity [ Time Frame: 1 year ]
    Dose limiting toxicity measured by adverse events and serious adverse events will be reviewed by dose level by the Safety Oversight Committee and will result in a recommended Phase 2 dose.
  • Efficacy of HPN536 at the recommended Phase 2 dose: overall response rate (ORR) [ Time Frame: 2 years ]
    Evaluate overall response rate (ORR) as assessed by Prostate Cancer Working Group 3 (PCWG3) criteria
Change History
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Study of HPN536 in Patients With Advanced Cancers Associated With Mesothelin Expression
Official Title  ICMJE 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
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.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Advanced Cancers Associated With Mesothelin Expression
Intervention  ICMJE Biological: HPN536
Dose escalation: HPN536 will be administered once weekly via IV infusion Dose expansion: HPN536 will be administered at the RP2D once weekly via IV infusion
Study Arms  ICMJE
  • Experimental: HPN536-2001 - Part 1 (Dose Escalation)
    Part 1 (Dose Escalation): will include eligible patients with epithelial ovarian cancer, fallopian tube cancer, primary peritoneal cancer, pancreatic adenocarcinoma, or malignant mesothelioma. HPN536 will be administered once weekly via IV infusion with a fix dose. Dose escalation per cohort until an estimated therapeutic dose level has been reached.
    Intervention: Biological: HPN536
  • Experimental: HPN536-2001 - Part 2 (Dose Expansion)

    Part 2 (Dose Expansion): will include eligible patients with epithelial ovarian cancer, fallopian tube cancer, primary peritoneal cancer, malignant mesothelioma, pancreatic adenocarcinoma or malignant mesothelioma. HPN536 will be administered once weekly via IV infusion.

    Group 1: Eligible patients with epithelial ovarian cancer, fallopian tube cancer, or primary peritoneal cancer.

    Group 2: Eligible patients with pancreatic adenocarcinoma.

    Group 3: Eligible patients with mesothelioma.

    Intervention: Biological: HPN536
Publications * 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.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: April 12, 2021)
180
Original Estimated Enrollment  ICMJE
 (submitted: March 12, 2019)
87
Estimated Study Completion Date  ICMJE May 1, 2022
Estimated Primary Completion Date April 1, 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE
  1. Patients ≥18 years of age
  2. One of the following progressive advanced or metastatic cancers:

    1. Epithelial ovarian, fallopian tube, or primary peritoneal cancer (Part 1 and Part 2, Group 1 only) that is platinum refractory or platinum resistant
    2. Pancreatic adenocarcinoma (Part 1 and Part 2, Group 2 only) that is locally advanced, and now with progressive disease on or after front-line treatment
    3. Malignant mesothelioma with epithelioid histology, pleural (Part 1 and Part 2, Group 3 only) or primary peritoneal (Part 1 and Part 2, Group 3 only)
  3. 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
  4. Available archival tissue sample or fresh biopsy tissue sample must be obtained prior to enrollment
  5. 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 5 half-lives, whichever is longer, prior to start of study drug. The maximum washout period will not exceed 4 weeks
  6. ECOG performance status of 0 or 1
  7. 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) ≥10 g/dL
  8. Adequate renal function, including estimated creatinine clearance ≥30 mL/min
  9. 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
  10. Serum albumin as follows:

    1. ≥30 mg/mL for patients with epithelial ovarian cancer, fallopian tube cancer, primary peritoneal cancer, or mesothelioma
    2. Within normal limits for patients with pancreatic adenocarcinoma
  11. Patients with pancreatic adenocarcinoma: C-reactive protein (CRP) within normal limits

Key Exclusion Criteria:

  1. Previously treated or current brain metastases. Note: 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. Concurrent treatment with anti- TNFα therapies, systemic corticosteroids, or other immune suppressive drugs within the 2 weeks prior to Screening
  3. Patients with pancreatic adenocarcinoma: Any ascites within 1 month prior to screening
  4. History of or known or suspected autoimmune disease
  5. History of clinically significant cardiovascular disease
  6. Pulmonary, hematologic, renal, hepatic, gastrointestinal, neurological or psychiatric disease that would limit compliance with study requirements
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Harpoon Therapeutics (650) 443-7400 HPN5362001@harpoontx.com
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03872206
Other Study ID Numbers  ICMJE HPN536-2001
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Harpoon Therapeutics
Study Sponsor  ICMJE Harpoon Therapeutics
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account Harpoon Therapeutics
Verification Date April 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP