Phase 1b/2 BreakVax personalized neoantigen vaccine + PD-1 and CTLA-4 blockade immunotherapy

BreakBio Corp’s Phase 1b/2 study tests a multi-component regimen built around BreakVax, a per-patient manufactured personalized vaccine intended to prime tumor-specific T cells (a neoantigen peptide immunotherapy) in advanced triple-negative breast cancer. BreakVax is given with Montanide and Poly-ICLC as vaccine adjuvants, plus low-dose subcutaneous ipilimumab (a Bristol Myers Squibb CTLA-4–blocking antibody) injected locally at the vaccine site to enhance dendritic cell priming. Pembrolizumab (Merck’s PD-1–blocking antibody) is added later in the schedule to reduce T-cell exhaustion and sustain effector function, while patients also receive physician’s-choice chemotherapy (tumor cell killing that can increase antigen release and immunogenic cell death). Losartan (an angiotensin II type 1 receptor blocker) and aspirin (a COX-inhibiting NSAID) are included as tumor–microenvironment modulators aimed at stromal/vascular remodeling and reducing immunosuppressive signaling. Eligible patients are locally advanced unresectable or metastatic TNBC that is PD-L1–negative (CPS <10) and germline BRCA–negative, after progression on first-line ADC therapy; today’s care is sequential single-agent chemotherapy (often with later-line sacituzumab govitecan or other ADCs depending on prior exposure) with limited benefit in PD-L1–negative disease, and this study asks whether individualized vaccination plus checkpoint blockade can create meaningful responses beyond chemo alone.