Clinical Summary:

• Design/Population: Phase 2 OrigAMI-4 study evaluating subcutaneous amivantamab monotherapy in 102 patients with HPV-unrelated recurrent/metastatic head and neck squamous cell carcinoma whose disease progressed after platinum-based chemotherapy and PD-(L)1 inhibitor treatment.
• Key Outcomes: Amivantamab achieved a confirmed objective response rate of 47%, including 4 complete responses, with a median duration of response of 7.2 months and median progression-free survival of 6.8 months; responses were rapid, occurring within a median of 6.6 weeks.
• Clinical Relevance: These findings suggest that dual EGFR/MET targeting with amivantamab may offer a promising treatment option for patients with HPV-unrelated recurrent/metastatic HNSCC who have limited therapeutic options after progression on immunotherapy and chemotherapy, with a manageable safety profile consistent with prior experience.

Barbara Burtness, MD, FASCO, Yale Cancer Center, New Haven, Connecticut, presents findings from the phase 2 OrigAMI-4 study evaluating subcutaneous amivantamab monotherapy in patients with HPV-unrelated recurrent/metastatic head and neck squamous cell carcinoma whose disease had progressed after platinum-based chemotherapy and PD-(L)1 inhibition. 

Amivantamab achieved a confirmed objective response rate of 47%, with rapid and durable responses, including 4 complete responses, and a median progression-free survival of 6.8 months. Dr Burtness also discusses the treatment’s manageable safety profile, which was consistent with previous reports and supported its potential as a treatment option in this difficult-to-treat population. 

Dr Burtness presented these findings at the 2026 ASCO Annual Meeting in Chicago, Illinois.

Transcript:

Hi, my name is Barbara Burtness. I'm a professor of medical oncology at Yale School of Medicine and my interest is in head and neck cancer. This year in ASCO, I presented the results of cohort one of the OrigAMI-4 trial. This was a study that looked at subcutaneous administration of the EGFR-MET bispecific antibody amivantamab in patients with recurrent metastatic head and neck cancer.

In cohort 1, patients received amivantamab monotherapy and the cohort was restricted to patients who had p16-negative head neck cancer that was recurrent metastatic and had previously been treated with an immune checkpoint inhibitor and platinum chemotherapy. The initial results of the first 39 patients in this cohort had previously been presented and they showed an investigator-assessed response rate of 45%. Now we're presenting the full cohort, which is 102 patients. This represents the same patient population recurrent metastatic previously treated p16-negative.

What we found was that the investigator-assessed response rate was 47%. This was confirmed at 42% by blinded independent central review. Overall, subcutaneous amivantamab was very well tolerated so there were about 15% of infusion reactions all grade 1 to 2. Most common side effects were those that are already associated with EGFR and MET inhibitors, so things like hypoalbuminemia and acneoform skin rash. There was only 1 treatment-related death that was from pneumonitis. Overall, 6 patients from this heavily pretreated cohort died on study. The median overall survival was 12.5 months and remember this is secondline. 12- and 18-month progression-free survival were over 20%.

Overall, this looked like deep and durable responses for a very heavily pretreated patient population. These data are being submitted to the FDA. They've been simultaneously published in the Journal of Clinical Oncology and taking these data together with the results of cohort 2 from this trial, which were presented by Dr. Ranee Mehra at the Head and Neck Multidisciplinary Meeting in February where the combination had a response rate of 56%.

This agent is now moving into firstline testing in recurrent metastatic disease in the phase 3 trial, the OrigAMI-5. Here patients who have p16-negative cancer will be randomized to either get amivantamab plus pembrolizumab and carboplatin or to get the reference standard from KEYNOTE-048 pembrolizumab plus doublet chemotherapy.

Overall it looks like amivantamab has very high single agent activity, combines well with pembrolizumab, is quite tolerable, and we look forward to future results with the OrigAMI-5 study.

Source:

Burtness B, Harrington KJ, Ji D, et al. Amivantamab in HPV-unrelated recurrent/metastatic head and neck squamous cell cancer after disease progression on immune checkpoint inhibitor and chemotherapy: Pivotal results from the phase 1b/2 OrigAMI-4 study. Presented at the ASCO Annual Meeting. May 29 - June 2, 2026. Chicago, Illinois. Abstract 4513.