Early Phase 1 mitazalimab CD40 agonist +/− nivolumab PD-1 inhibitor intratumoral in resectable breast cancer

This early Phase 1 “window-of-opportunity” study tests whether a single intratumoral injection of mitazalimab (a CD40 agonistic monoclonal antibody that activates antigen-presenting cells to enhance T-cell priming) given alone or with intratumoral nivolumab (a PD-1 checkpoint–blocking monoclonal antibody) is safe and biologically active when administered ≥7 days before surgery. It’s an open-label, dose-escalation design (with defined dose levels and a de-escalation option if dose-limiting toxicities occur) in stage I–III, resectable breast cancer, focusing on feasibility (including avoiding unplanned surgical delays) plus immune, histologic, and pathologic effects. The program is notable for local, pre-op immune modulation rather than systemic dosing, aiming to turn the intact tumor into an in situ vaccine-like stimulus. Mitazalimab is developed by Alligator Bioscience, and nivolumab (Opdivo) is from Bristol Myers Squibb. Today’s care for stage I–III breast cancer is surgery with risk-adapted perioperative systemic therapy (endocrine therapy for HR+ disease; chemotherapy ± anti-HER2 therapy for HER2+; and for higher-risk TNBC, chemo plus perioperative pembrolizumab), whereas this study probes whether localized CD40 activation ± PD-1 blockade can amplify antitumor immunity in the brief pre-surgical window.