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Study in Patients With Advanced Cancers Associated With Expression of DLL3

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 : December 12, 2023
Sponsor:
Information provided by (Responsible Party):
Harpoon Therapeutics

Study Description
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Brief Summary:
A Phase 1/2 Open-label, Multicenter, Dose Escalation and Dose Expansion Study of the Safety, Tolerability, and Pharmacokinetics of HPN328 Monotherapy and HPN328 With Atezolizumab in Patients With Advanced Cancers Associated With Expression of Delta-like Canonical Notch Ligand 3 (DLL3)

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

Study Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 162 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 Monotherapy and HPN328 With Atezolizumab in Patients With Advanced Cancers Associated With Expression of Delta-like Canonical Notch Ligand 3 (DLL3)
Actual Study Start Date : December 29, 2020
Estimated Primary Completion Date : January 2024
Estimated Study Completion Date : June 2024

Resource links provided by the National Library of Medicine


Arms and Interventions
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Arm Intervention/treatment
Experimental: HPN328 monotherapy dose escalation
HPN328 will be administered as a single agent once weekly via IV infusion during each 21 day cycle.
 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: HPN328 monotherapy dose escalation with extended dosing intervals
HPN328 will be administered as a single agent, via IV infusion either once every 2 weeks (28-day cycle), or once every 3 weeks (21-day cycle).
 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: HPN328 dose escalation in combination with atezolizumab
SCLC patients will be treated with a combination regimen of HPN328 and atezolizumab. HPN328 will be administered once every 2 weeks via IV infusion during each 28-day cycle. Atezolizumab will be administered once every 4 weeks via IV infusion on Day 1 of each 28-day cycle.
 Drug: HPN328
HPN328 is a tri-specific recombinant protein construct (Tri-specific T Cell Activating Construct [TriTAC®]) containing 3 humanized antibody derived binding domains

Drug: Atezolizumab
Atezolizumab is a humanized immunoglobulin (Ig) G1 monoclonal antibody which potently and selectively inhibits binding of programmed death receptor 1 ligand (PD-L1) on tumor cells and tumor infiltrating immune cells in the tumor microenvironment


Outcome Measures
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Primary Outcome Measures :
  1. Frequency and severity of treatment-emergent AEs (TEAEs) graded according to NCI CTACAE version 5.0 (ASTCT grading criteria for CRS and ICANS). [ Time Frame: Up to 4 years ]
  2. Number and severity of DLTs following treatment with HPN328 as monotherapy or in combination with atezolizumab. [ Time Frame: Up to 4 years ]
  3. PK parameters of HPN328 as monotherapy or in combination with atezolizumab. [ Time Frame: Up to 4 years ]
    • Single dose - maximum concentration, time to maximum concentration, area under the single dose concentration-time curve over the dosing interval, area under the concentration-time curve extrapolated to infinity, terminal elimination half-life, and clearance as data permit
    • Multiple dose (assuming stead state is achieved) - maximum concentration at steady state, time to maximum concentration, area under the steady state concentration-time curve over dosing interval, terminal elimination half-life, minimum concentration, clearance, volume of distribution, and accumulation ratio as data permit.


Secondary Outcome Measures :
  1. Change from baseline in selected clinical laboratory parameters, vital signs, and ECGs. [ Time Frame: Up to 4 years ]
  2. Objective response rate (ORR) based on RECIST v1.1 (PCWG3 for patients with NEPC) [ Time Frame: Up to 4 years ]
  3. Extra-cranial objective response rate (EC-ORR) based on modified RECIST v1.1 [ Time Frame: Up to 4 years ]
  4. Best Overall Response (BOR) [ Time Frame: Up to 4 years ]
  5. Progression-free survival (PFS) [ Time Frame: Up to 4 years ]
  6. Extra-cranial progression free survival (EC-PFS) [ Time Frame: Up to 4 years ]
  7. Overall survival (OS) [ Time Frame: Up to 4 years ]
  8. Duration of response (DOR) [ Time Frame: Up to 4 years ]
  9. Duration of extra-cranial response (EC-DOR) [ Time Frame: Up to 4 years ]
  10. Incidence and titers of ADAs against HPN328 and atezolizumab (for combination-treatment patients) [ Time Frame: Up to 4 years ]

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 which is relapsed/refractory following at least 1 prior line of systemic therapy that included platinum-based chemotherapy
    • Neuroendocrine Prostate Cancer (NEPC; de novo or treatment-emergent) which is relapsed/refractory to standard systemic therapy
    • High-grade neuroendocrine tumor types other than SCLC and NEPC has at least of the following:
    • Disease that is relapsed/refractory to standard systemic therapy,
    • Disease for which standard therapy does not exist, or
    • Disease for which standard therapy is not considered appropriate by the Investigator

  2. Available archival tissue sample or fresh biopsy tissue sample

    1. For SCLC and NEPC: must be available for shipment prior to enrollment but confirmation of DLL3 expression is not required prior to enrollment.
    2. For high-grade neuroendocrine tumor types other than SCLC and NEPC: demonstration of DLL3 expression in a tumor sample is required and must be confirmed prior to screening.

  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 central nervous system (CNS) metastases. Patients with history of CNS metastases can participate provided they are pretreated and radiologically stable (i.e., without evidence of progression) for at least 2 weeks by repeated imaging (note: repeated imaging should be performed during study screening), asymptomatic, and without requirement of steroid treatment for at least 7 days before the first dose of study treatment.
  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. History of intracranial hemorrhage or spinal cord hemorrhage.
  5. Active neurologic paraneoplastic syndrome.
  6. Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures (e.g., biweekly or more frequently).
  7. Active or history of autoimmune disease or immune deficiency, including, but not limited to, myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, psoriatic arthritis, inflammatory bowel disease, antiphospholipid antibody syndrome, Wegener granulomatosis, Sjögren's syndrome, Guillain-Barré syndrome, or multiple sclerosis. Exceptions apply.
  8. Ongoing treatment with immunosuppressive medications (including, but not limited to, systemic corticosteroids [prednisone dose >10mg per day or equivalent], cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-tumor necrosis factor [TNF] alpha agents) within 2 weeks prior to initiation of treatment, or anticipation of need for systemic immunosuppressive medication during study treatment (except protocol-required pre-medications). Exceptions apply.
  9. History of allogeneic stem cell transplant or solid-organ transplant.

  10. For patients enrolled in the HPN328/Atezolizumab combination cohorts:

    • Known hypersensitivity to biopharmaceuticals produced in Chinese hamster ovary cells or any component of the atezolizumab formulation, or other anti-PD-(L)1 agents.
    • Treatment with systemic immunostimulatory agents (including, but not limited to, interferon and IL-2) within 4 weeks or 5 drug-elimination half-lives (whichever is longer) prior to initiation of study treatment.
    • History of severe anaphylactic reactions to chimeric or humanized antibodies or fusion proteins.
    • History of idiopathic pulmonary fibrosis, organizing pneumonia (e.g., bronchiolitis obliterans), drug-induced pneumonitis, or idiopathic pneumonitis, or evidence of active pneumonitis on screening chest computed tomography (CT). History of radiation pneumonitis in the radiation field is permitted.
Contacts and Locations
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Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

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, California
Cedar-Sinai Medical Center, Samuel Oschin Comprehensive Cancer Institute Recruiting
Los Angeles, California, United States, 90048
Contact: Garrett Crook    424-314-0745    Garrett.Crook@cshs.org   
Principal Investigator: Kanya Sankar, MD         
University of California San Francisco Recruiting
San Francisco, California, United States, 94143
Contact: Christopher De Leon    415-307-9861    chris.deleon@ucsf.edu   
United States, Colorado
University of Colorado Recruiting
Aurora, Colorado, United States, 80045
Contact: Emma Filar    702-848-9206    EMMA.FILAR@CUANSCHUTZ.EDU   
Principal Investigator: Erin Schenk, 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: Aaron Le    313-576-8912    lea@karmanos.org   
Principal Investigator: Hirva Mamdani, MD         
United States, New York
Roswell Park Comprehensive Cancer Center Recruiting
Buffalo, New York, United States, 14263
Contact: Janine Miller    716-845-2809    janine.miller@RoswellPark.org   
Principal Investigator: Prantesh Jain, MD         
Memorial Sloan Kettering Cancer Center Recruiting
New York, New York, United States, 10021
Contact: Noura Choudury, MD       choudhn2@mskcc.org   
Principal Investigator: Noura Choudury, 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   
Principal Investigator: Melissa L. Johnson, MD         
United States, Wisconsin
Medical College of Wisconsin Recruiting
Milwaukee, Wisconsin, United States, 53226
Contact: Jonathan Thompson, MD       jrthomps@mcw.edu   
Principal Investigator: Jonathan Thompson, 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: December 12, 2023
Last Verified: December 2023

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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
Atezolizumab
Immune Checkpoint Inhibitors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents, Immunological
Antineoplastic Agents