ASCO 2026: OrigAMI-4 Phase 2 — Amivantamab Achieves 42% Response Rate in Checkpoint-Refractory Head and Neck Cancer

Phase 1b/2 data from the OrigAMI-4 trial, presented at ASCO 2026 by Johnson & Johnson, showed that amivantamab (Rybrevant FASPRO) — a subcutaneously administered bispecific antibody targeting EGFR and MET — achieved a 42% confirmed objective response rate in 102 patients with HPV-unrelated recurrent or metastatic head and neck squamous cell carcinoma (HNSCC) who had progressed on both immune checkpoint inhibitor and platinum-based chemotherapy. More than one-third of responders achieved a complete response, and the median duration of response had not been reached at a median follow-up of 11.8 months — suggesting durable responses in this heavily pre-treated population with poor prognosis. Recurrent/metastatic HNSCC following checkpoint inhibitor failure represents a difficult-to-treat setting where no standard of care exists, and historical response rates to subsequent therapies are typically below 15%. Amivantamab's dual EGFR/MET blockade is mechanistically attractive in HNSCC, where EGFR is overexpressed in 90%+ of tumors and MET amplification is a common mechanism of resistance to EGFR inhibition. J&J announced it will evaluate a pivotal trial in this indication based on the OrigAMI-4 data, and the FDA previously granted amivantamab Breakthrough Therapy Designation for HNSCC. The Rybrevant FASPRO subcutaneous formulation enables administration in approximately 5–8 minutes versus 2–5 hour IV infusions.