Intratumoral Mitazalimab with or without Nivolumab for the Treatment of Recurrent Resectable Breast Cancer, WINIT-BC

Inclusion Criteria

• Signed and dated written institutional review board (IRB)-approved informed consent
• Age ≥ 18 years
• Body weight > 30kg
• Stage I-III or recurrent resectable breast cancer to be treated with curative-intent
• Planning to undergo upfront surgery as part of routine clinical care
• Discussion with the treating or study medical oncologist re: the potential of sending an Oncotype evaluation (if estrogen receptor positive [ER+] HER2-) on the core needle biopsy sample
• Availability of the core needle biopsy sample for correlative studies
• Surgery to be performed at a University of Pennsylvania Hospital
• Life expectancy of at least 12 weeks
• ANC (absolute neutrophil count) ≥ 1.5 x 10^9 cell/ml (within 4 weeks prior to administration of study treatment)
• Platelets ≥ 75,000/mm^3 (within 4 weeks prior to administration of study treatment)
• Hemoglobin ≥ 9.0 g/dL (within 4 weeks prior to administration of study treatment)
• Total serum bilirubin within 1.5 x upper limit of normal (ULN) (within 4 weeks prior to administration of study treatment) unless Gilbert's
• Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) within 2.5 x ULN (within 4 weeks prior to administration of study treatment)
• Albumin ≥ 3 g/dL (within 4 weeks prior to administration of study treatment)
• Electrocardiogram (ECG) with no clinically significant findings as assessed by the investigator
• ECOG (Eastern Cooperative Oncology Group) performance status of 0-1
• Female patients of childbearing potential who are not abstinent and intend to be sexually active with a non-sterilized male partner must use at least 1 highly effective method of contraception from the time of screening throughout the total duration of the drug treatment and the drug washout period (90 days after therapy). Non-sterilized male partners of a female patient of childbearing potential must use male condom plus spermicide throughout this period. Female patients should also refrain from breastfeeding throughout this period
• Able and willing to comply with all study procedures

Exclusion Criteria

• Metastatic disease
• HER2+ breast cancer
• Planned neoadjuvant therapy, i.e., not undergoing upfront surgery
• Known history of hepatitis B or C with active viral replication
• Administration of any live vaccine within 28 days of first dose of study treatment
• Prior CD40 or anti-PD-1 agonist therapy
• Participation in another interventional clinical trial within 30 days before receiving first dose of study treatment. However, the subject may participate in observational studies
• Any illness or condition that in the opinion of the investigator may affect the safety of the subject or the evaluation of any study endpoint
• Current or prior use of immunosuppressive medication within 14 days before study treatment. The following are exceptions to this criterion: * Intranasal, inhaled, topical steroids, or local steroid injections (e.g., intra articular injection) * Systemic corticosteroids at physiologic doses not to exceed 10 mg/day of prednisone or its equivalent
• Major surgical procedure (as defined by the investigator) within 28 days prior to the first dose of investigational product (IP)
• History of allogeneic organ transplantation
• Active or prior documented autoimmune disease. Examples include inflammatory bowel disease (e.g., colitis or Crohn's disease), systemic lupus erythematosus, sarcoidosis syndrome, or Wegener syndrome (granulomatosis with polyangiitis), Graves' disease, rheumatoid arthritis, hypophysitis, uveitis, etc. The following are exceptions to this criterion: * Patients with vitiligo or alopecia * Patients with hypothyroidism (e.g., following Hashimoto syndrome) stable on hormone replacement or type 1 diabetes mellitus (DM) controlled with insulin * Any chronic skin condition that does not require systemic therapy * Patients without active autoimmune disease in the last 5 years may be included but only after consultation with the study physician * Patients with celiac disease controlled by diet alone
• Uncontrolled intercurrent illness, including but not limited to, ongoing or active infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, cardiac arrhythmia, interstitial lung disease, serious chronic gastrointestinal conditions associated with diarrhea, or psychiatric illness/social situations that would limit compliance with study requirement, substantially increase risk of incurring adverse events (AEs) or compromise the ability of the patient to give written informed consent
• History of another active malignancy except for non-melanoma skin cancer, lentigo maligna or other carcinoma in situ
• History of active primary immunodeficiency
• Known allergy or hypersensitivity to any of the study drugs or any of the study drug excipients
• Body weight > 110 kg