A Phase I Safety and Immunogenicity Trial of MVA-BN®-HER2 Vaccine in HER-2-Positive Breast Cancer Patients Following Adjuvant Therapy
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 15
- 试验地点
- 2
- 主要终点
- Number and type of adverse events as a measure of safety and tolerability of multiple vaccinations
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •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®-HER
- •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,
- •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®-HER
- •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.
- •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
排除标准
- •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®-HER
- •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
研究组 & 干预措施
MVA-BN-HER2
干预措施: MVA-BN-HER2 (Biological)
结局指标
主要结局
Number and type of adverse events as a measure of safety and tolerability of multiple vaccinations
时间窗: 18 months
次要结局
- Type and duration of immune response measured over time to repeat vaccine administrations(18 months)