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Study in Patients With Advanced Cancers Associated With Expression of DLL3 Who Have Failed Standard Available Therapy

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: NCT04471727
Recruitment Status : Recruiting
First Posted : July 15, 2020
Last Update Posted : January 12, 2022
Sponsor:
Information provided by (Responsible Party):
Harpoon Therapeutics

Study Description
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Brief Summary:
An open-label, Phase 1/2 study of HPN328 as monotherapy to assess the safety, tolerability and PK in patients with advanced cancers associated with expression of DLL3.

Condition or disease Intervention/treatment Phase
Small-cell Lung Cancer Drug: HPN328 Phase 1 Phase 2

Study Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 57 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: Single (Participant)
Primary Purpose: Treatment
Official Title: A Phase 1/2 Open-label, Multicenter, Dose Escalation and Dose Expansion Study of the Safety, Tolerability, and PK of HPN328 in Patients With Advanced Cancers With Expression of DLL3 Who Have Failed Standard Available Therapy
Actual Study Start Date : December 29, 2020
Estimated Primary Completion Date : December 2022
Estimated Study Completion Date : March 2023

Resource links provided by the National Library of Medicine


Arms and Interventions
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Arm Intervention/treatment
Experimental: Part 1 (Dose Escalation)
HPN328 is IV administered once weekly for about 1 hour. Doses will vary between cohorts as MTD is being determined.
 Drug: HPN328
HPN328 is a tri-specific recombinant protein construct (Tri-specific T Cell Activating Construct [TriTAC®]) containing 3 humanized antibody derived binding domains
Experimental: Part 2 (Dose Expansion)
HPN328 is IV administered once weekly for about 1 hour at the recommended phase 2 dose (2) established in Part 1.
 Drug: HPN328
HPN328 is a tri-specific recombinant protein construct (Tri-specific T Cell Activating Construct [TriTAC®]) containing 3 humanized antibody derived binding domains


Outcome Measures
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Primary Outcome Measures :
  1. Assessment of Adverse Events by CTCAE 5.0 of HPN 328 [ Time Frame: 3 years ]
    Assess safety and tolerability at increasing dose levels of HPN328 in successive cohorts of patients with solid tumors associated with DLL3 expression 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. Characterize the pharmacokinetics (PK) of HPN328 [ Time Frame: 2 years ]
    Evaluate of levels of HPN328 in blood serum


Secondary Outcome Measures :
  1. Determine preliminary activity of HPN328 [ Time Frame: 3 years ]
    Evaluate preliminary efficacy of HPN328 based on disease assessment using RECISTv1.1

  2. Determine the immunogenicity [ Time Frame: 3 years ]
    Evaluate the immunogenicity of HPN328 assessing Anti-drug Antibodies in blood serum


Eligibility Criteria
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Ages Eligible for Study:   18 Years to 100 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Major Inclusion Criteria:

  1. Histologically or cytologically confirmed malignancy associated with expression of DLL3:

    • SCLC that has relapsed following at least 1 line of platinum-based chemotherapy
    • Malignancy other than SCLC with pathologic demonstration of high-grade neuroendocrine features or demonstration of DLL3 expression in a tumor sample, and that the patient has 1 of the following:
    • Disease that is relapsed/refractory to standard systemic therapy,
    • Disease for which standard therapy does not exist, or
    • Disease where standard therapy is not considered appropriate by the Investigator
  2. Available archival tissue sample or fresh biopsy tissue sample must be available for shipment prior to enrollment. Patients with no available tumor tissue, who cannot safely undergo a biopsy may be eligible if they have documentation of DLL3 expression in a tumor sample from a prior biopsy.

  3. Adequate hematologic status, including:

    • Absolute neutrophil count (ANC) ≥1500 cells/μL
    • Platelet count ≥100,000/μL
    • Hemoglobin ≥9 g/dL (no transfusions allowed within 2 weeks prior to screening)

  4. Adequate renal function, including:

    -Calculated creatinine clearance ≥50 mL/min using the formula of Cockcroft and Gault

  5. Adequate liver function, including

    • Total bilirubin ≤1.5 x upper limit of normal (ULN), regardless of direct bilirubin, unless the patient has documented Gilbert syndrome in which case the maximum total serum bilirubin should be 5 mg/dL
    • Aspartate and alanine transaminase (AST and ALT) ≤3 x ULN

Major Exclusion Criteria:

  1. Untreated brain metastases. Participants must have completed treatment for brain metastasis, and be neurologically stable off steroids, for at least 7 days prior to first dose of study drug
  2. Patients with glioma or other primary CNS malignancy
  3. Patients with spinal cord compression or symptomatic/uncontrolled epidural disease. Patients with previously treated spinal cord compression or epidural disease may be eligible if stable for at least 1 week prior to first dose of study drug.
  4. Active neurologic paraneoplastic syndrome.
  5. Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures (e.g., biweekly or more frequently).
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04471727


Contacts
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Contact: Harpoon ClinicalTrials.gov Contact (650) 452-7280 hpn328_4001ctgov@harpoontx.com

Locations
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United States, Colorado
University of Colorado Recruiting
Aurora, Colorado, United States, 80045
Contact: Josh Saginaw, RN, BSN    720-848-9281    JOSHUA.SAGINAW@CUANSCHUTZ.EDU   
Principal Investigator: Jose Pacheco, MD         
United States, Massachusetts
Dana Farber Cancer Institute Recruiting
Boston, Massachusetts, United States, 02467
Contact: Himisha Beltran, MD    617-632-2429    Himisha_Beltran@DFCI.HARVARD.EDU   
Principal Investigator: Himisha Beltran, MD         
United States, Michigan
Karmanos Cancer Center Recruiting
Detroit, Michigan, United States, 48201
Contact: Kelly Schneider    313-576-9749    schneidk@karmanos.org   
United States, Missouri
Washington University School of Medicine St. Louis Withdrawn
Saint Louis, Missouri, United States, 63110
United States, New York
Roswell Park Comprehensive Cancer Center Recruiting
Buffalo, New York, United States, 14263
Contact: RUSHKA KALLICHARAN-SMITH, BA, CCRP    716-845-1300 ext 2809    Rushka.Kallicharan-Smith@RoswellPark.org   
Principal Investigator: Grace Dy, MD         
Memorial Sloan Kettering Cancer Center Recruiting
New York, New York, United States, 10021
Contact: Adam Schoenfeld, MD    646-608-4042    schoenfa@mskcc.org   
Principal Investigator: Adam Schoenfeld, MD         
United States, Ohio
University Hospitals Cleveland Medical Center Recruiting
Cleveland, Ohio, United States, 44106
Contact: Cancer Information Services    800-641-2422    Kyle.Logue@uhhospitals.org   
Principal Investigator: Afshin Dowlati, MD         
United States, Oregon
Providence Recruiting
Portland, Oregon, United States, 97213
Contact       CanRsrchStudies@providence.org   
Principal Investigator: Rachel Sanborn, MD         
United States, Tennessee
Tennessee Oncology Recruiting
Nashville, Tennessee, United States, 37203
Contact: Tennessee Oncology Sarah Cannon Research Institute    615-329-7478    cann.researchreferrals@scresearch.net   
United States, Wisconsin
Medical College of Wisconsin Recruiting
Milwaukee, Wisconsin, United States, 53226
Contact: Smitha Menon, MD    414-805-4600    spmenon@mcw.edu   
Principal Investigator: Smitha Menon, MD         
Sponsors and Collaborators
Harpoon Therapeutics
More Information
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Responsible Party: Harpoon Therapeutics
ClinicalTrials.gov Identifier: NCT04471727    
Other Study ID Numbers: HPN328-4001
First Posted: July 15, 2020    Key Record Dates
Last Update Posted: January 12, 2022
Last Verified: November 2021

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Harpoon Therapeutics:
Lung Cancer
Small-Cell Lung Cancer
DLL3
Harpoon
TriTAC
 Prostate Cancer
Neuroendocrine Tumors
High Grade Neuroendrocrine Features
Delta Like Canonical Notch Ligand 3
Additional relevant MeSH terms:
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Lung Neoplasms
Small Cell Lung Carcinoma
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
 Neoplasms
Lung Diseases
Respiratory Tract Diseases
Carcinoma, Bronchogenic
Bronchial Neoplasms