A Safety and Immunology Study of a Modified Vaccinia Vaccine for HER-2(+) Breast Cancer After Adjuvant Therapy

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

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 HER-2-positive breast cancer.

The intent of vaccination is to induce a combined antibody and T-cell anti-HER-2 immune response, which is intended to target HER-2-expressing tumor cells, and may induce tumor regression or slow progression of disease.

Study Overview

• Status: Completed
• Conditions: Breast Cancer
• Intervention / Treatment: Biological: MVA-BN-HER2

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 15
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • Berkeley, California, United States, 94704
      • Alta Bates Comprehensive Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: MVA-BN-HER2	Biological: MVA-BN-HER2; experimental vaccine, subcutaneous injection q4weeks x6

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Number and type of adverse events as a measure of safety and tolerability of multiple vaccinations	18 months

Secondary Outcome Measures

Outcome Measure	Time Frame
Type and duration of immune response measured over time to repeat vaccine administrations	18 months

Collaborators and Investigators

• Sponsor: Bavarian Nordic
• Investigators: Study Director: Olga Bandman, Bavarian Nordic

Study record dates

Study Major Dates

• Study Start: June 1, 2010
• Primary Completion (Actual): September 1, 2012
• Study Completion (Actual): September 1, 2012

Study Registration Dates

• First Submitted: June 25, 2010
• First Submitted That Met QC Criteria: June 28, 2010
• First Posted (Estimate): June 29, 2010

Study Record Updates

• Last Update Posted (Actual): March 14, 2019
• Last Update Submitted That Met QC Criteria: March 12, 2019
• Last Verified: August 1, 2011

More Information

Terms related to this study

• Keywords: Vaccine; Breast cancer; Phase I; Metastatic; HER-2 Positive Breast Cancer; HER-2-positive
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms
• Other Study ID Numbers: BNIT-BR-003