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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 : November 25, 2020
Sponsor:
Information provided by (Responsible Party):
Harpoon Therapeutics

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

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 52 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 Pharmacokinetics of HPN328 in Patients With Advanced Cancers Associated With Expression of Delta Like Canonical Notch Ligand 3 (DLL3) Who Have Failed Standard Available Therapy
Estimated Study Start Date : November 2020
Estimated Primary Completion Date : December 2022
Estimated Study Completion Date : March 2023

Resource links provided by the National Library of Medicine


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




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



Information from the National Library of Medicine

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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).

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


Locations
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United States, Tennessee
Tennessee Oncology Recruiting
Nashville, Tennessee, United States, 37203
Contact: Tennessee Oncology Sarah Cannon Research Institute    844-482-4812      
Sponsors and Collaborators
Harpoon Therapeutics
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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: November 25, 2020
Last Verified: June 2020

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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