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A Phase I Safety and Immunogenicity Trial of MVA-BN®-HER2 Vaccine in HER-2-Positive Breast Cancer Patients Following Adjuvant Therapy


Phase 1
18 Years
N/A
Not Enrolling
Female
Breast Cancer

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Trial Information

A Phase I Safety and Immunogenicity Trial of MVA-BN®-HER2 Vaccine in HER-2-Positive Breast Cancer Patients Following Adjuvant Therapy


MVA-BN®-HER2 is a candidate breast cancer immunotherapy product comprised of a highly
attenuated non-replicating vaccinia virus, MVA-BN®, engineered to encode a modified form of
the HER-2 protein.

MVA-BN® is a well-characterized, clonal strain of modified vaccinia virus Ankara (MVA) being
developed as a smallpox vaccine, suitable for use in high-risk (e.g., immunocompromised)
individuals. MVA-BN®-derived vectors encoding heterologous antigens are being developed for
use as vaccines for infectious diseases such as HIV, and for the treatment of cancer. A
large database exists from safety evaluations in animals and in humans for MVA-BN®, and
MVA-BN®-derived vectors.

HER-2 is overexpressed in 20-30% of human breast cancers. It is an oncogene/growth factor
receptor critical for the malignant phenotype of HER-2- expressing tumors. It is an
immunogenic target, and immune responses to this protein have been shown to mediate potent
anti-tumor activity in multiple animal models. Means to stimulate anti-HER-2 reactivity are
now being studied clinically. Sponsor, collaborators, and others have used both Protein and
DNA vaccine forms of HER-2, and a safety database is developed and no significant adverse
events have resulted from HER-2 directed vaccination.

MVA-BN®-HER2 encodes a modified form of the HER-2 protein, hereinafter referred to as HER2.
HER2 contains the extracellular domain of HER-2 but lacks the intracellular, cell signaling
domain. In addition, HER2 includes two universal T-cell epitopes from tetanus toxin to
facilitate the stimulation of an immune response to HER-2, a self-protein.

The current trial, BNIT-BR-003, will evaluate the safety and biological activity of a fixed
dose of MVA-BN®-HER2 following adjuvant chemotherapy in patients with breast cancers which
overexpress HER-2.

Patients will receive 6 subcutaneous vaccinations at 4-week intervals and will have blood
drawn for immune function analysis.


Inclusion Criteria:



- Signed Informed Consent

- Women, ≥ 18 years of age

- Histologically documented, HER-2-positive breast cancer without metastatic disease.
Hormone receptor (ER/PR) status may be either positive or negative. HER-2
(+) status may be determined by one of the following measurements:

- Immunohistochemistry 3+ or FISH/CISH+ (HER-2 gene signal to centromere 17 signal >
2). NOTE: HER-2 assessment may have been on initial diagnosis and need not be
repeated.

- Patients should be assessed as having no evidence of disease (NED) at the end of
adjuvant chemotherapy. In addition, these patients must have a clinical evaluation
and lab work as standard of care disease assessment without evidence of recurrence
within 28 days of the first planned dose of MVA-BN®-HER2.

- Completed adjuvant and/or neoadjuvant chemotherapy for breast cancer at least 3
months previously (measured from the date of the last dose of chemotherapy) and prior
to the first planned dose of MVA-BN®-HER2).

- ECOG Performance Score of 0, 1.

- Predicted life expectancy ≥ 12 months

- Left ventricular ejection fraction (LVEF) by ECHO ≥ LLN as defined by institutional
standards

- Women of childbearing potential must:

- have a negative serum or urine pregnancy test, and

- must agree to use a medically acceptable barrier and/or chemical method of
contraception throughout the study treatment period and for 28 days after the
last dose of MVA-BN®-HER2.

- No significant cardiac, bone marrow dysfunction, or coagulopathy (defined as no Grade
3 or greater AE according to NCI CTCAE v 3.0). No significant hepatic or renal
dysfunction (defined as no Grade 2 or greater AE according to NCI CTCAE v 3.0.
Patients with a known history of a CLINICALLY NON-SIGNIFICANT laboratory parameter
may be eligible for inclusion provided an exemption is granted by the study Medical
Monitor prior to enrollment.

- A negative virology screen for HIV, HBsAg, and HCV

Exclusion Criteria:

- Congestive heart failure (NYHA Class III or IV), unstable angina, or cardiovascular
disease such as stroke or myocardial infarction (current or within the past 6 months)

- History of cardiac toxicity secondary to chemotherapy or Herceptin immunotherapy
(LVEF decline of 15% or greater from baseline)

- History of prior malignancies other than breast cancer within the past 5 years,
excluding basal or squamous cell carcinoma of the skin or carcinoma in situ of the
cervix

- Any breast cancer metastases beyond the lymph nodes

- Known allergy to eggs, egg products, or aminoglycoside antibiotics, e.g., gentamicin
or tobramycin

- Chronic administration (defined as 6 or more consecutive days of use) of systemic
corticosteroids within 14 days of the first planned dose of MVA-BN®-HER2. Limited use
of inhaled steroids, nasal sprays, eye drops, and topical creams for small body areas
is allowed.

- History of or active autoimmune disease. Persons with vitiligo or thyroid disease
taking thyroid replacement hormones are not excluded.

- Prior solid organ or hematopoietic allogenic transplant(s)

- Prior use of hematopoietic growth factors (e.g., GM-CSF) within 14 days of the first
planned dose of MVA-BN®-HER2

- Receipt of an investigational agent within 28 days of the first planned dose of
MVA-BN®-HER2

- Prior "vaccine" therapy for breast cancer at any time

- Vaccination:

Live (attenuated) vaccine (e.g., FluMist®) Vaccination with a live vaccine within 28 days
of the first planned dose of MVA-BN®-HER2, or plans to receive a live vaccine within 28
days after the last dose of MVA-BN®-HER2 is not allowed Killed (inactivated) vaccine
(e.g.,PneumoVax®) Vaccination with a killed vaccine within 14 days of the first planned
dose of MVA-BN®-HER2, or plans to receive a killed vaccine within 14 ' days after the last
dose of MVA-BN®-HER2 is not allowed

- A maximum cumulative dose of prior doxorubicin > 360 mg/m2 or epirubicn > 720 mg/m2

- Radiation therapy within 14 days of the first planned dose of MVA-BN®-HER2 or plans
for radiation therapy after enrollment. Prior to initiating palliative radiation
during the treatment phase of the study, the Sponsor's medical monitor or designee
must be contacted.

- Pregnant, lactating, or nursing

- Any condition which, in the opinion of the investigator, would prevent full
participation in this trial or the long-term follow-up study, or would interfere with
the evaluation of the trial endpoints

Type of Study:

Interventional

Study Design:

Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Number and type of adverse events as a measure of safety and tolerability of multiple vaccinations

Outcome Time Frame:

18 months

Safety Issue:

Yes

Principal Investigator

Olga Bandman

Investigator Role:

Study Director

Investigator Affiliation:

BN ImmunoTherapeutics

Authority:

United States: Food and Drug Administration

Study ID:

BNIT-BR-003

NCT ID:

NCT01152398

Start Date:

June 2010

Completion Date:

September 2012

Related Keywords:

  • Breast Cancer
  • Breast cancer
  • Vaccine
  • Metastatic
  • HER-2-positive
  • Phase I
  • HER-2 Positive Breast Cancer
  • Breast Neoplasms

Name

Location

Alta Bates Comprehensive Cancer CenterBerkeley, California  94704