Summary

Eligibility
for people ages 18-100 (full criteria)
Location
at San Francisco, California and other locations
Dates
study started
completion around

Description

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)

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)

Keywords

Small-Cell Lung Cancer, Neuroendocrine Carcinoma, Lung Cancer, DLL3, Harpoon, TriTAC, Prostate Cancer, Neuroendocrine Tumors, High Grade Neuroendrocrine Features, Delta Like Canonical Notch Ligand 3, T-cell Engager, Lung Neoplasms, Small Cell Lung Carcinoma, Atezolizumab, HPN328

Eligibility

For people ages 18-100

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 treatment.
  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 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.
  11. History of interstitial lung disease, 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.
  12. Treatment with other investigational drug within 3 weeks of scheduled dosing (or 5 half-lives of drug, whichever is shorter).

Locations

  • UCSF accepting new patients
    San Francisco California 94143 United States
  • Cedar-Sinai Medical Center, Samuel Oschin Comprehensive Cancer Institute accepting new patients
    Los Angeles California 90048 United States

Details

Status
accepting new patients
Start Date
Completion Date
(estimated)
Sponsor
Harpoon Therapeutics
ID
NCT04471727
Phase
Phase 1/2 research study
Study Type
Interventional
Participants
Expecting 162 study participants
Last Updated