Window of Opportunity Study of Intratumoral CD40 Agonist (Mitazalimab) With or Without PD-1 Inhibitor (Nivolumab) in Patients With Resectable Breast Cancer (WINIT-BC)
The goal of this clinical trial is to study the safety, feasibility, histologic and immunological effects of Mitazalimab, a CD40 agonistic antibody, when administered either alone or in combination with PD-1 inhibition prior to surgical resection. The investigator hypothesizes that preoperative administration of CD40 agonist with or without PD-1 inhibitor intratumorally will demonstrate an acceptable safety profile, will not result in an unplanned delay in surgery, and will lead to increased immune activation. Subjects will receive a single intratumoral dose of CD40 agonist with or without PD-1 inhibitor 7 or more days prior to surgery and will be followed for safety, feasibility, immune, and pathologic responses.
• Signed and dated written IRB-approved informed consent.
• Age ≥18 years.
• Body weight \> 40kg
• 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 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.
⁃ Adequate bone marrow, hepatic, and renal function. ANC (Absolute Neutrophil Count) ≥ 1.5x109 cell/ml, platelets ≥75,000 /mm3, hemoglobin ≥9.0 g/dL, total serum bilirubin within 1.5 x upper limit of normal (ULN) unless Gilbert's, AST/ALT, within 2.5 x ULN, Albumin ≥3g/dL, and all tests performed within 4 weeks prior to administration of Study Treatment.
⁃ 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.