Clinical trial NCT03872206: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Advanced Cancers Associated With Mesothelin Expression
Lead sponsor: Harpoon Therapeutics, Inc., a subsidiary of Merck & Co., Inc. (Rahway, New Jersey USA)
Sponsor class: INDUSTRY
First posted: 2019-03-13
Enrollment: 95
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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.)


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 based on 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.

Primary outcomes:
measure: Assessment of Adverse Events by CTCAE 5.0 of HPN536
timeFrame: 3 years
measure: Determine MTD/RP2D
timeFrame: 2 years
measure: Efficacy of HPN536 at the recommended Phase 2 dose: overall response rate (ORR)
timeFrame: 1 year
Secondary outcomes:
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Mayo Clinic Arizona
state: Arizona
city: Los Angeles
country: United States
facility: University of Southern California
state: California
city: Los Angeles
country: United States
facility: University of California Los Angeles
state: California
city: Jacksonville
country: United States
facility: Mayo Clinic Florida
state: Florida
city: Chicago
country: United States
facility: University of Chicago
state: Illinois
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Rochester
country: United States
facility: Mayo Clinic Rochester
state: Minnesota
city: Saint Louis
country: United States
facility: Washington University School of Medicine in St. Louis
state: Missouri
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
city: Cleveland
country: United States
facility: Cleveland Clinic Taussig Cancer Institute
state: Ohio
city: Oklahoma City
country: United States
facility: Stephenson Cancer Center
state: Oklahoma
city: Philadelphia
country: United States
facility: Thomas Jefferson University
state: Pennsylvania
city: Nashville
country: United States
facility: Sarah Cannon Research Institute
state: Tennessee
city: Dallas
country: United States
facility: Mary Crowley Cancer Research
state: Texas
city: Charlottesville
country: United States
facility: University of Virginia Cancer Center
state: Virginia
city: Seattle
country: United States
facility: University of Washington Medical Center
state: Washington
Study officials:
References:
citation: 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.