1. Written informed consent and any locally-required authorization (e.g., HIPAA) obtained
from the subject prior to performing any protocol-related procedures, including
2. Age =/> 18 years at time of study entry
3. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
4. Clinical Stage II-III as assessed by AJCC guidelines (8th Edition, Anatomic Staging)
with no known metastatic disease (includes hormone receptor negative breast cancer).
-Tumor size > 2 cm and/or lymph node positive
5. HER2+, breast cancer as defined by ASCO-CAP guidelines: HER2/neu is defined as
positive: IHC 3+ based on circumferential membrane staining that is complete, intense
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.
6. continued #5: Adequate normal organ and marrow function as defined below: - Hemoglobin
=/> 9 g/dL - Absolute neutrophil count (ANC) =/>1.5 x 10^9/L (=/> 1500 per mm³) -
Platelet count =/> 100 x 10^9/L (=/> 100,000 per mm³)- 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. -AST (SGOT)/ALT (SGPT) </= 2.5 x institutional upper limit of normal
7. continued # 5:Serum creatinine clearance >/= 60 mL/min by the Cockcroft-Gault formula
or by 24-hour urine collection for determination of creatinine clearance: Males:
Creatinine clearance (mL/min) = Weight (kg) x (140 minus Age) 72 x serum creatinine
(mg/dL) Females: Creatinine clearance (mL/min) = Weight (kg) x (140 minus Age) x0.85
72 x serum creatinine (mg/dL)
8. 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).
9. continued # 8: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.
10. 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
1. Involvement in the planning and/or conduct of the study (applies to both EMD Serono
staff and/or staff at the study site)
2. Participation in another clinical study with an investigational product during the
last 1 month prior to initiation of therapy
3. Any previous treatment with a PD-1 or PD-L1 inhibitor or CTLA-4 inhibitor
4. 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
5. Has received therapy for this current diagnosis of breast cancer including endocrine
therapy or chemotherapy.
6. Mean QT interval corrected for heart rate (QTc) =/> 470 ms
7. 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
8. 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.
9. Active or prior documented inflammatory bowel disease (e.g., Crohn's disease,
10. History of primary immunodeficiency
11. History of organ transplants that require immunosuppression
12. History of hypersensitivity to M7824 or any excipient of M7824
13. 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
14. Active tuberculosis
15. Receipt of live attenuated vaccination within 30 days prior to study entry or within
30 days of receiving M7824
16. 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.
17. Subjects with uncontrolled seizures.
18. Concurrent treatment with non-permitted drugs and other interventions.
19. Any major surgery for any reason, except diagnostic biopsy, within 4 weeks of the
20. Inflammatory breast cancer
>change in tumor-infiltrating lymphocytes (TIL) percentage pre and post M7824
>Assessed using core biopsy tissue obtained prior to dose 1 of study drug
and repeat biopsy obtained 2 weeks after dose 2 of study drug
>Adverse Events (AE) with M7824
>Start of M7824
therapy up to 90 days after last dosetd><td
>AE is any untoward medical occurrence in a subject or clinical investigation subject administered a pharmaceuticalproduct
, regardless of causal relationship with this treatment.
AE determined by the NCI-CTCAE v4.03.td>
>Pathological Response with M7824
>56 days after completing chemotherapyatsurgery