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

Tracking Information

• First Submitted Date: March 11, 2019
• First Posted Date: March 13, 2019
• Last Update Posted Date: September 13, 2022
• Actual Study Start Date: April 16, 2019
• Estimated Primary Completion Date: February 1, 2023 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: April 4, 2022)

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

• Current Secondary Outcome Measures: Not Provided
• Original Secondary Outcome Measures: Not Provided
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Study of HPN536 in Patients With Advanced Cancers Associated With Mesothelin Expression
• 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
• 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: Interventional
• Study Phase: Phase 1; Phase 2
• Study Design: Allocation: Non-Randomized; Intervention Model: Sequential Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Advanced Cancers Associated With Mesothelin Expression

Intervention

• 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
• 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

Study Arms

• 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.
  Intervention: Biological: HPN536
• 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
  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.

Recruitment Information

• Recruitment Status: Active, not recruiting
• Estimated Enrollment (submitted: April 4, 2022): 200
• Original Estimated Enrollment (submitted: March 12, 2019): 87
• Estimated Study Completion Date: May 1, 2023
• Estimated Primary Completion Date: February 1, 2023 (Final data collection date for primary outcome measure)

Eligibility 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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT03872206
• Other Study ID Numbers: 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: Not Provided
• Current Responsible Party: Harpoon Therapeutics
• Original Responsible Party: Same as current
• Current Study Sponsor: Harpoon Therapeutics
• Original Study Sponsor: Same as current
• Collaborators: Not Provided
• Investigators: Not Provided
• PRS Account: Harpoon Therapeutics
• Verification Date: September 2022