OrigAMI-4 Cohort 1 Study Design Overview

Paul L. Swiecicki, MD, of the University of Michigan Rogel Cancer Center, outlines the design of the phase 1b/2 OrigAMI-4 study, an umbrella trial evaluating subcutaneous amivantamab across multiple settings in recurrent or metastatic head and neck squamous cell carcinoma (HNSCC), including first-line disease, platinum-refractory disease, and platinum-and-immune-checkpoint-inhibitor (ICI)-refractory disease. He focuses on cohort 1, the fully enrolled 102-patient population published in the Journal of Clinical Oncology in 2026, which evaluated single-agent amivantamab in patients who had progressed on platinum-based chemotherapy, whether platinum-resistant in the metastatic or locally advanced setting, and on ICI given in the metastatic setting. Dr Swiecicki explains that the primary endpoint was overall response rate, benchmarked against a historical rate of approximately 10% with agents such as cetuximab or taxanes, with secondary endpoints including progression-free survival (PFS), overall survival (OS), depth of response, and toxicity outcomes.