Clinical Trials /

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

NCT04471727

Description:

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.

Related Conditions:
  • Malignant Solid Tumor
  • Small Cell Lung Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

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

Clinical Trial IDs

  • ORG STUDY ID: HPN328-4001
  • NCT ID: NCT04471727

Conditions

  • Small-cell Lung Cancer

Interventions

DrugSynonymsArms
HPN328Part 1 (Dose Escalation)

Purpose

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.

Trial Arms

NameTypeDescriptionInterventions
Part 1 (Dose Escalation)ExperimentalHPN328 is IV administered once weekly for about 1 hour. Doses will vary between cohorts as MTD is being determined.
  • HPN328
Part 2 (Dose Expansion)ExperimentalHPN328 is IV administered once weekly for about 1 hour at the recommended phase 2 dose (2) established in Part 1.
  • HPN328

Eligibility 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).
      
Maximum Eligible Age:100 Years
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Assessment of Adverse Events by CTCAE 5.0 of HPN 328
Time Frame:3 years
Safety Issue:
Description: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)

Secondary Outcome Measures

Measure:Determine preliminary activity of HPN328
Time Frame:3 years
Safety Issue:
Description:Evaluate preliminary efficacy of HPN328 based on disease assessment using RECISTv1.1
Measure:Determine the immunogenicity
Time Frame:3 years
Safety Issue:
Description:Evaluate the immunogenicity of HPN328 assessing Anti-drug Antibodies in blood serum

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Harpoon Therapeutics

Trial Keywords

  • Lung Cancer
  • Small-Cell Lung Cancer
  • DLL3
  • Harpoon
  • TriTAC
  • Prostate Cancer
  • Neuroendocrine Tumors
  • High Grade Neuroendrocrine Features
  • Delta Like Canonical Notch Ligand 3

Last Updated

December 8, 2020