A Study of pING-hHER3FL Vaccine in Cancer Patients With Advanced Malignancies
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|ClinicalTrials.gov Identifier: NCT03832855|
Recruitment Status : Not yet recruiting
First Posted : February 6, 2019
Last Update Posted : February 8, 2019
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.
|Condition or disease||Intervention/treatment||Phase|
|Advanced Cancer||Biological: pING-hHER3FL||Phase 1|
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.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||18 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Phase I Study of Active Immunotherapy With pING-hHER3FL Vaccine in Patients With Advanced or Metastatic Malignancies|
|Estimated Study Start Date :||May 15, 2019|
|Estimated Primary Completion Date :||June 1, 2021|
|Estimated Study Completion Date :||June 1, 2022|
4 mg pING-hHER3FL ID or IM
Plasmid vaccine containing HER3
- Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability] [ Time Frame: 12 weeks ]Adverse Event Assessment to determine Safety and tolerability of pING-hHER3FL vaccination
- Rate of T and B cell activity [ Time Frame: 12 months ]B cell and T cell specific immune response to pING-hHER3FL vaccination
- Percent of cells expressing HER3, STAT3, MAPK, PI3K [ Time Frame: 12 months ]Evaluate for markers of HER3 expression and activation
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): NCT03832855
|Contact: Michael Morse, MDfirstname.lastname@example.org|
|Contact: Beth Hollister, BSN, RNemail@example.com|