CMP-001 and Pre-operative Stereotactic Body Radiation Therapy (SBRT) in Early Stage Triple Negative Breast Cancer (TNBC)

Prior treatment

• Breast-feeding women
  • Medical history and concurrent diseases:
• Developed autoimmune disorders of Grade 4 while on prior immunotherapy. Subjects who developed autoimmune disorders of Grade ≤ 3 may enroll if the disorder has resolved to Grade ≤ 1 and the subject has been off systemic steroids for at least 2 weeks.
• Any concurrent uncontrolled illness, including mental illness or substance abuse, which in the opinion of the Investigator, would make the subject unable to cooperate and participate in the trial
• Severe uncontrolled cardiac disease within 6 months before Screening, including but not limited to uncontrolled hypertension; unstable angina; myocardial infarction (MI) or cerebrovascular accident (CVA)
• Any prior ipsilateral breast irradiation.
• Received investigational therapy with another drug or biologic within 28 days prior to treatment study.
• Require systemic pharmacologic doses of corticosteroids at or above the equivalent of 10 mg/day prednisone; replacement doses, topical, ophthalmologic and inhalational steroids are permitted. Subjects who are currently receiving steroids at a dose of \< 10 mg/d do not need to discontinue steroids prior to randomization.
• For arm 2: Requires concomitant treatment with warfarin. Other anticoagulants (ie, low molecular weight heparins, non-steroidal anti-inflammatory drugs) are allowed as long as the institutional guidelines requiring their withholding for interventional radiology procedures can be followed.
• Administration of a live, attenuated vaccine within 2 weeks before randomization.

Other illness

• History of malignancy other than TNBC within 5 years prior to screening, with the exception of malignancies with a negligible risk of metastasis or death (e.g., 5-year OS rate \>90%), such as adequately treated carcinoma of the cervix in situ, non-melanoma skin carcinoma, ductal carcinoma in situ, or Stage I uterine cancer
• Known infection with human immunodeficiency virus (HIV), hepatitis B virus (HBV) or hepatitis C virus (HCV)
• Active autoimmune disease:
  • Participants with well controlled asthma and/or mild allergic rhinitis (seasonal allergies) are eligible
  • Participants with the following disease conditions are also eligible:
  • Vitiligo
  • Type 1 diabetes mellitus
  • Residual hypothyroidism due to autoimmune condition only requiring hormone replacement
  • Psoriasis not requiring systemic treatment conditions not expected to recur in the absence of an external trigger are permitted to enroll
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to CMP-001
• Any history of adrenal deficiency
  • Prohibited treatments and/or therapies:
• Requires prohibited treatment (i.e., non-protocol specified anticancer pharmacotherapy, surgery or conventional radiotherapy for treatment of malignant tumor).

Other

• Subjects presenting with any of the following do not qualify for entry into the study:

• Signed study Informed Consent Form prior to the initiation of any study procedures
• Women age ≥18 years
• Histologically confirmed diagnosis of triple negative breast cancer (TNBC) of early stage (cT1b-2, cN0-3b cM0) determined according to immunohistochemistry (IHC) / in situ hybridization (ISH). TNBC subtype is defined as:
  • Estrogen receptor (ER) \<10%
  • Progesterone receptor (PR) \<10%
  • Human epidermal growth factor receptor 2 (HER2) negative (not eligible for anti-HER2 therapy) defined as:
  • IHC 0, 1+ without ISH or
  • IHC 2+ and ISH non-amplified with ratio less than 2.0 and if reported, average HER2 copy number \< 6 signals/cells or
  • ISH non-amplified with ratio less than 2.0 and if reported, average HER2 copy number \< 6 signals/cells (without IHC)
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1.
• Women with bilateral breast TNBC can be acceptable if both sides are TNBC (treatment is allowed to be administered to one breast only).
• Capable of understanding and complying with protocol requirements
• A planned breast surgery (Breast conserving surgery \[BCS\] or mastectomy) or neoadjuvant chemotherapy.
• Presence of measurable disease in the breast, defined as a lesion that can be accurately measured in at least one dimension with conventional techniques (Magnetic resonance imaging \[MRI\] and/or ultrasound)
• Primary tumor accessible to injections and biopsy. Multifocal and multicentric disease is allowed and the most accessible lesion will be injected. The lesion to be injected should be confined in a single irradiation volume that does not result in more than 30% of the whole breast.
• The injected tumor should be located at least 5 mm from the skin or pectoral muscle
• Most recent laboratory values (within 28 days prior to randomization) meet the following standards:
  • Bone marrow function:
  • neutrophil count ≥1.5 G/L
  • hemoglobin ≥ 90 g/L
  • platelet count ≥ 100 G/L
  • Liver function:
  • total bilirubin within normal ranges of each institution (except patients with Gilbert's syndrome who must have total bilirubin \< 3.0 mg/dL)
  • aspartate aminotransferase (AST) ≤ 2.5 times the ULN range.
  • alanine aminotransferase (ALT) ≤ 2.5 times the ULN range
  • Renal function: estimated glomerular filtration rate (eGFR) ≥ 40 ml/min/1.73 m2 (according to Chronic Kidney Disease Epidemiology Collaboration \[CKD-EPI\] formula)
• For women of childbearing potential (WOCBP):
  • Agreement to use an acceptable method of effective contraception from screening until 30 days after last study treatment (RT and CMP-001).
  • WOCBP must have a negative urine/blood pregnancy test within 7 days before randomization. A positive urine test must be confirmed by a serum pregnancy test.