Head & neck cancers / Clinical Insights 06/06/2026

Amivantamab Demonstrates Promising Activity in Heavily Pretreated Disease

An image of a professional woman with shoulder-length blonde hair, wearing yellow glasses and a black top, against a dark background, representing oncology research and expertise. Barbara Burtness, MD Paul Swiecicki, MD Ari Rosenberg, MD Jessica Geiger, MD Smiling man with beard wearing a white shirt, professional headshot, suitable for oncology or cancer research content, emphasizing healthcare and medical expertise. Rahul Gosain, MD, MBA Oncologist smiling in white coat, highlighting cancer research and treatment expertise, with a bow tie, in a bright medical setting. Rohit Gosain, MD

Key Points

  • Amivantamab targets both EGFR and MET pathways to overcome resistance signaling.
  • OrigAMI-4 showed response rates of approximately 42% to 45%, including complete responses in about 15% of patients, in later-line therapy.
  • Responses appear rapid and may be durable in heavily pretreated patients.
  • Human papillomavirus (HPV)–negative disease remains a major unmet clinical subgroup.

During a Clinical Insights session on head and neck cancer coinciding with the 2026 American Society of Clinical Oncology (ASCO) Annual Meeting in Chicago, Oncology Brothers podcast cohosts Rahul Gosain, MD, MBA, of Wilmot Cancer Institute, and Rohit Gosain, MD, of Roswell Park Comprehensive Cancer Center, led a Clinical Insights session on head and neck cancer. They were joined by Barbara Burtness, MD, of Yale School of Medicine; Ari Rosenberg, MD, of the University of Chicago; Paul Swiecicki, MD, of University of Michigan Health; and Jessica Geiger, MD, of Cleveland Clinic.

Continuing the discussion, Dr. Burtness described how resistance to EGFR inhibition often occurs through bypass signaling mechanisms, including activation of HER family signaling and upregulation of MET-driven pathways. After emphasizing that these mechanisms support dual-targeted therapeutic strategies, she discussed amivantamab as a bispecific antibody targeting both EGFR and MET. She explained that the agent is designed to bind both receptors and promote receptor internalization, which may reduce compensatory signaling that drives resistance, and noted potential immune-mediated effects that may contribute to tumor response.

The discussion then turned to OrigAMI-4 clinical data presented at ASCO 2026. Dr. Geiger noted that in cohort 1, which evaluated single-agent subcutaneous amivantamab in recurrent metastatic disease, patients were heavily pretreated, with many receiving third-line or later therapy. The observed objective response rate was 42% to 45%, with approximately 15% of patients achieving complete responses. She emphasized that this level of activity is notable in a refractory population, and early signals also suggest potential durability of response.

Dr. Burtness added that responses appeared rapid and clinically meaningful, and median overall survival exceeded 12 months in early analyses. Dr. Rosenberg contextualized these results against historical cetuximab outcomes, emphasizing that prior EGFR-targeted therapy typically achieves response rates around 20% to 25%. The panel agreed that OrigAMI-4 represents a potential advance in later-line treatment, and HPV-negative disease was highlighted as a key subgroup with unmet need.