ARX788 + cemiplimab

ARX788 + cemiplimab appears to be a combination therapy being investigated for breast cancer treatment. ARX788 is an antibody-drug conjugate (ADC) targeting HER2, while cemiplimab is a PD-1 inhibitor. This combination is being evaluated in clinical trials, particularly in the neoadjuvant setting for HER2-positive early-stage breast cancer. The combination therapy is being studied in the I-SPY 2.2 trial, which is an adaptive Phase 2 clinical trial evaluating emerging targeted agents. ARX788 is being assessed both as a monotherapy and in combination with cemiplimab for HER2-positive early-stage breast cancer before surgery (neoadjuvant setting). ## Drug Details ARX788 is a novel HER2-targeted monoclonal antibody linked to the cytotoxic payload AS269. It uses a synthetic amino acid para-acetylphenylalanine (pAF) incorporated into a predetermined site on the heavy chain of the anti-HER2 monoclonal antibody, allowing for conjugation of diverse payloads. This technology creates a homogeneous and highly stable ADC that maximizes potential anti-tumor activity by optimizing the number and position of payloads and the chemical bonds that conjugate them to the antibody. In preclinical studies, ARX788 demonstrated activity in HER2-positive, HER2-low, and T-DM1 resistant tumors. Clinical trials have shown it to be well-tolerated, with most adverse events being grade 1 or 2. The most common grade >3 adverse events were ocular events (5.7%) and pneumonitis (4.3%) in one trial, and pneumonitis (2.9%) and fatigue (2.9%) in another. Cemiplimab is a PD-1 targeting checkpoint inhibitor that works by enhancing the immune system's ability to detect and destroy cancer cells.