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.
Title
- Brief Title: Assessing the Immunogenicity of pING-hHER3FL
- Official Title: Assessing the Immunogenicity of pING-hHER3FL in Patients With Resected Malignancies
Clinical Trial IDs
- ORG STUDY ID:
Pro00104093
- NCT ID:
NCT03832855
Conditions
Interventions
Drug | Synonyms | Arms |
---|
pING-hHER3FL | | Treatment |
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
Name | Type | Description | Interventions |
---|
Treatment | Experimental | 4 mg pING-hHER3FL ID or IM | |
Eligibility Criteria
Inclusion Criteria:
- Documented history of solid tumor 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 in the literature). Demonstration of
HER3 expression is not required for enrollment.
- Has undergone surgical resection of malignancy and has completed intended standard
course of chemotherapy and HER2 targeted therapy and radiotherapy under the direction
of their physician. Subjects may continue on adjuvant hormonal therapy.
- Has no evidence of disease by standard imaging studies (performed at the direction of
their physician) within 60 days prior to initiating study treatment.
- Between 3 weeks and 2 years since prior cytotoxic chemotherapy, HER2-targeted therapy
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.
- 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:
- Patients must have recovered to Grade 1 toxicities from any prior treatment(s).
- 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.
- Prior immunotherapy
Maximum Eligible Age: | N/A |
Minimum Eligible Age: | 18 Years |
Eligible Gender: | All |
Healthy Volunteers: | No |
Primary 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 vaccinationvaccination |
Secondary Outcome Measures
Measure: | Tolerability of pING-hHER3FL |
Time Frame: | 12 weeks |
Safety Issue: | |
Description: | Assessment of adverse events in response to pING-hHER3FL |
Measure: | Relapse-free survival |
Time Frame: | 5 years |
Safety Issue: | |
Description: | Time until relapse of cancer |
Details
Phase: | Phase 1 |
Primary Purpose: | Interventional |
Overall Status: | Recruiting |
Lead Sponsor: | Herbert Lyerly |
Last Updated
July 23, 2020