Clinical Trials /

A Study of pING-hHER3FL Vaccine in Cancer Patients With Advanced Malignancies

NCT03832855

Description:

This study is a phase I clinical trial will that will use an investigational cancer vaccine called pING-hHER3FL. pING-hHER3FL is a circular piece of DNA that produces the full length human HER3 protein and will be used in a phase I study as immunotherapeutic agent to target cancers that are known to express the human epidermal growth factor receptor HER3. The human epidermal growth factor receptor (HER) family including: HER1 (also known as EGFR), HER2, HER3 and HER4 (also known as ErbB2, ErbB3, and ErbB4 respectively) is an important receptor family for the development of many malignancies. HER3 is overexpressed in breast, lung, gastric, head and neck, ovarian cancer, and melanoma. The objectives of this clinical study is to determine the safety and tolerability of pING-hHER3FL in patients with advanced or metastatic solid tumor malignancies and to test whether immunization with pING-hHER3FL can cause a HER3 specific immune response in patients. Patients enrolled in the study will receive pING-hHER3FL by intramuscular injection (IM) every 4 weeks for 3 total doses. Potential benefits of the research include learning the safety of a vaccine targeting HER3 expressing cancers, whether the pING-hHER3FL vaccine can induce HER3 specific immune responses, and see possible clinical benefit to patients receiving pING-hHER3FL.

Related Conditions:
  • Malignant Solid Tumor
Recruiting Status:

Not yet recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: A Study of pING-hHER3FL Vaccine in Cancer Patients With Advanced Malignancies
  • Official Title: A Phase I Study of Active Immunotherapy With pING-hHER3FL Vaccine in Patients With Advanced or Metastatic Malignancies

Clinical Trial IDs

  • ORG STUDY ID: Pro00101933
  • NCT ID: NCT03832855

Conditions

  • Advanced Cancer

Interventions

DrugSynonymsArms
pING-hHER3FLTreatment

Purpose

This study is a phase I clinical trial will that will use an investigational cancer vaccine called pING-hHER3FL. pING-hHER3FL is a circular piece of DNA that produces the full length human HER3 protein and will be used in a phase I study as immunotherapeutic agent to target cancers that are known to express the human epidermal growth factor receptor HER3. The human epidermal growth factor receptor (HER) family including: HER1 (also known as EGFR), HER2, HER3 and HER4 (also known as ErbB2, ErbB3, and ErbB4 respectively) is an important receptor family for the development of many malignancies. HER3 is overexpressed in breast, lung, gastric, head and neck, ovarian cancer, and melanoma. The objectives of this clinical study is to determine the safety and tolerability of pING-hHER3FL in patients with advanced or metastatic solid tumor malignancies and to test whether immunization with pING-hHER3FL can cause a HER3 specific immune response in patients. Patients enrolled in the study will receive pING-hHER3FL by intramuscular injection (IM) every 4 weeks for 3 total doses. Potential benefits of the research include learning the safety of a vaccine targeting HER3 expressing cancers, whether the pING-hHER3FL vaccine can induce HER3 specific immune responses, and see possible clinical benefit to patients receiving pING-hHER3FL.

Detailed Description

      The human epidermal growth factor receptor (HER) family including HER1 (also known as EGFR),
      HER2, HER3 and HER4 (also known as ErbB2, ErbB3, and ErbB4 respectively) is an important
      receptor family for the development of many malignancies. HER3 is overexpressed in breast,
      lung, gastric, head and neck, and ovarian cancer and melanoma and its overexpression is
      associated with poor prognosis. Because of the negligible tyrosine kinase function of HER3,
      it is typically present in heterodimers with HER1 or HER2, through which downstream signaling
      occurs involving extracellular-signal-regulated kinase (ERK) 1/2 and AKT. In breast cancer,
      HER3 is associated with resistance to anti-HER2 therapeutics. HER3 is also one of several
      important causes of endocrine resistance in breast cancer.

      A HER3 specific cancer vaccine that induces polyclonal antibody and T cell responses can
      provide long term anti-HER3 immune responses and potentially prevent the emergence of
      resistant clones. In addition to the long term protection afforded by vaccination, polyclonal
      immune responses to a target protein may offer additional benefits. It has been established
      that the binding of multiple antibodies to different epitopes is more efficient than a single
      monoclonal antibody in mediating receptor internalization. Additionally, T cell responses
      induced by vaccination are also a potent mechanism of tumor rejection in numerous animal
      studies and the adoptive transfer of T cells in human clinical trials has shown clinical
      efficacy. Although HER3 is expressed on a number of normal tissues, and is only rarely
      mutated in cancers, it remains an attractive immunotherapeutic target as it is not abundant
      on the cell surface in normal cells, tumor cells may have higher levels of membrane-bound
      HER3, and HER3 peptides are presented on the cell surface by MHC complexes for presentation
      to T cells.

      The primary objective of the study is to evaluate the safety of immunization with pING-hHER3
      in patients with advanced or metastatic solid tumor malignancies. The study will also monitor
      immune responses to HER3 and preliminary data on survival and tumor response rate will be
      collected.
    

Trial Arms

NameTypeDescriptionInterventions
TreatmentExperimental4 mg pING-hHER3FL ID or IM
  • pING-hHER3FL

Eligibility Criteria

        Inclusion Criteria:

          -  Histologically confirmed metastatic or inoperable solid tumors where HER3 expression
             is expected (this includes breast, colon, lung, prostate, ovarian, cervical,
             endometrial, gastric, pancreatic, bladder, head and neck, liver, and esophageal
             cancer, but other tumors will be considered based on emerging HER3 expression data).

          -  Must have had tumor progression after 2 lines of standard therapy (as determined by
             the patient's oncologist). .

          -  At least 3 weeks since prior cytotoxic chemotherapy or radiotherapy to the start of
             study treatment.

          -  ECOG 0 or 1

          -  Estimated life expectancy > 3 months.

          -  Age ≥ 18 years.

          -  Adequate hematologic function, with ANC >1500/µL, Hemoglobin ≥ 9 g/dL, and Platelets ≥
             75,000/µL.

          -  Adequate renal and hepatic function, with Serum Creatinine < 1.5 mg/dL, Bilirubin <
             1.5 mg/dL (except for Gilbert's syndrome which will allow bilirubin ≤ 2.0 mg/dL), ALT
             and AST ≤ 2.5 x ULN or if liver metastases are present < 5 x ULN.

          -  Prior immunotherapy discontinued at least 3 months prior to the start of study
             treatment.

          -  Female patients must be of non-child-bearing potential or use effective contraception,
             .

          -  Labs performed as standard of care prior to signing consent can be used to fulfill
             eligibility requirements if they were performed within 4 weeks of the start of study
             treatment.

          -  Ability to understand and provide signed informed consent.

          -  Ability to return to the study site for adequate follow-up, as required by this
             protocol.

          -  Negative serum pregnancy test within 7 days prior to the start of study treatment, for
             women of childbearing potential only.

        Exclusion Criteria:

          -  Less than 3 weeks between any prior cytotoxic chemotherapy and/or radiotherapy and
             start of study treatment. Patients must have recovered to Grade 1 toxicities from
             prior treatment.

          -  Known CNS/brain metastases

          -  History of auto-immune disease such as, but not restricted to, inflammatory bowel
             disease, systemic lupus erythematosus, ankylosing spondylitis, scleroderma, or
             multiple sclerosis.

          -  Serious chronic or acute illness considered by the Principal Investigator to
             constitute an unwarranted high risk for investigational treatment.

          -  Medical or psychological impediment to probable compliance with the protocol.

          -  Concurrent or prior second malignancy (within the past 5 years) other than
             non-melanoma skin cancer, Carcinoma in situ of the bladder and cervix.

          -  Presence of active infection or systemic use of antimicrobials within 48 hours prior
             to the start of study treatment.

          -  Patients on continuous steroid therapy for at least 72 hours (or other continuous
             immunosuppressives such as azathioprine or cyclosporine A) are excluded on the basis
             of potential immune suppression.

          -  Presence of a known active acute or chronic infection including HIV or viral hepatitis
             (Hepatitis B and C).

          -  Pregnant or nursing women.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]
Time Frame:12 weeks
Safety Issue:
Description:Adverse Event Assessment to determine Safety and tolerability of pING-hHER3FL vaccination

Secondary Outcome Measures

Measure:Rate of T and B cell activity
Time Frame:12 months
Safety Issue:
Description:B cell and T cell specific immune response to pING-hHER3FL vaccination
Measure:Percent of cells expressing HER3, STAT3, MAPK, PI3K
Time Frame:12 months
Safety Issue:
Description:Evaluate for markers of HER3 expression and activation

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Herbert Lyerly

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