| Eligibility |
Inclusion Criteria:
- Written informed consent and any locally-required authorization (e.g., Health
Insurance Portability and Accountability Act [HIPAA]) obtained from the subject prior
to performing any protocol-related procedures, including screening evaluations
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
- Tumor size >= 2 cm and with no known distant metastatic disease
- HER2+, breast cancer as defined by American Society of Clinical Oncology
(ASCO)-College of American Pathologists (CAP) guidelines: HER2/neu is defined as
positive: immunohistochemistry (IHC) 3+ based on circumferential membrane staining
that is complete, intense in situ hybridization (ISH) positive based on: single-probe
average HER2 copy number >= 6.0 signals/cell. Dual-probe HER2/CEP17 ratio >= 2.0; with
an average HER2 copy number >= 4.0 signals/cell, dual-probe HER2/CEP17 ratio >= 2.0;
with an average HER2, copy number < 4.0 signals/cell, dual-probe HER2/CEP17 ratio <
2.0; with an average HER2, copy number >= 6.0 signals/cell, neoadjuvant systemic
therapy is planned and will include HER2 targeted therapy in combination with
chemotherapy of physician's choice
- Hemoglobin >= 9 g/dL
- Absolute neutrophil count (ANC) >= 1.5 x 10^9/L (>= 1500 per mm^3)
- Platelet count >= 100 x 10^9/L (>= 100,000 per mm^3)
- Serum bilirubin =< 1.5 x institutional upper limit of normal (ULN). This will not
apply to subjects with confirmed Gilbert's syndrome (persistent or recurrent
hyperbilirubinemia that is predominantly unconjugated in the absence of hemolysis or
hepatic pathology), who will be allowed only upon treating physician, principal
investigator (PI) or co-PI approval
- Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase
[SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT])
=< 2.5 x institutional upper limit of normal
- Serum creatinine clearance >= 60 mL/min by the Cockcroft-Gault formula or by 24-hour
urine collection for determination of creatinine clearance
- Female subjects must either be of non-reproductive potential (ie, post-menopausal by
history: >= 60 years old and no menses for >= 1 year without an alternative medical
cause; OR history of hysterectomy, OR history of bilateral tubal ligation, OR history
of bilateral oophorectomy) or must have a negative serum pregnancy test upon study
entry and be using highly effective contraception (that is, methods with a failure
rate of less than 1% per year) for both male and female subjects if the risk of
conception exists (Note: The effects of the trial treatment on the developing human
fetus are unknown; thus, women of childbearing potential and men must agree to use
highly effective contraception). Male subjects on study must also use highly effective
contraception. Highly effective contraception must be used 30 days prior to first
trial treatment administration, for the duration of trial treatment, and at least for
4 months after stopping trial treatment. Should a woman become pregnant or suspect she
is pregnant while she or her partner is participating in this trial, the treating
physician should be informed immediately
- Subject is willing and able to comply with the protocol for the duration of the study
including undergoing treatment and scheduled visits and examinations including follow
up
Exclusion Criteria:
- Involvement in the planning and/or conduct of the study (applies to both EMD Serono
staff and/or staff at the study site)
- Participation in another clinical study with an investigational product during the
last 1 month prior to initiation of therapy
- Any previous treatment with a PD-1 or PD-L1 inhibitor or CTLA-4 inhibitor
- History of another primary malignancy except for:
- Malignancy treated with curative intent and with no known active disease >= 1
year before the first dose of study drug and of low potential risk for recurrence
- Adequately treated non-melanoma skin cancer or lentigo maligna without evidence
of disease
- Adequately treated carcinoma in situ without evidence of disease eg, cervical
cancer in situ
- Has received therapy for this current diagnosis of breast cancer including endocrine
therapy or chemotherapy
- Mean QT interval corrected for heart rate (QTc) >= 470 ms
- Current or prior use of immunosuppressive medication within 28 days before the first
dose of M7824, with the exceptions of intranasal and inhaled corticosteroids or
systemic corticosteroids at physiological doses, which are not to exceed 10 mg/day of
prednisone, or an equivalent corticosteroid
- Active or prior documented autoimmune disease within the past 2 years NOTE: Subjects
with vitiligo, Grave's disease, or psoriasis not requiring systemic treatment (within
the past 2 years) are not excluded
- Active or prior documented inflammatory bowel disease (e.g., Crohn's disease,
ulcerative colitis)
- History of primary immunodeficiency
- History of organ transplants that require immunosuppression
- History of hypersensitivity to M7824 or any excipient of M7824
- Uncontrolled intercurrent illness including, but not limited to, ongoing or active
infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable
angina pectoris, cardiac arrhythmia, active peptic ulcer disease or gastritis, active
bleeding diatheses, known history of human immunodeficiency virus (HIV) and/or viral
hepatitis, or psychiatric illness/social situations that would limit compliance with
study requirements or compromise the ability of the subject to give written informed
consent
- Active tuberculosis
- Receipt of live attenuated vaccination within 30 days prior to study entry or within
30 days of receiving M7824
- Female subjects who are pregnant, breast-feeding or male or female patients of
reproductive potential who are not employing an effective method of birth control
- Subjects with uncontrolled seizures
- Concurrent treatment with non-permitted drugs and other interventions
- Any major surgery for any reason, except diagnostic biopsy, within 4 weeks of the
enrollment
- Inflammatory breast cancer
- History of conditions associated with bleeding diatheses
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