Head and Neck Cancer / Conferences 06/13/2026

Emerging Data on Amivantamab and Other Anti-EGFR Bispecifics in Head and Neck Cancer

Nicole Dalal, MD Nicole Dalal, MD Advanced cancer research professional smiling outdoors, representing oncology updates and medical breakthroughs in cancer treatment and research. Fangdi Sun, MD

Key Points

  • Amivantamab monotherapy demonstrated promising objective response and progression-free survival rates for head and neck cancer that progressed on chemoimmunotherapy in the OrigAMI-4 trial.
  • Amivantamab and other EGFR–directed bispecific antibodies are being investigated in first-line combinations for patients with recurrent or metastatic head and neck cancer.

Nicole Dalal, MD, and Fangdi Sun, MD, both of Stanford University, discussed the emerging role of EGFR–directed bispecific antibodies in the treatment of head and neck cancers, including data on amivantamab from the OrigAMI trials presented at the 2026 American Society of Clinical Oncology Annual Meeting (ASCO 2026).

Amivantamab is a bispecific antibody against EGFR and MET that has been approved for non-small cell lung cancer with certain EGFR mutations. The OrigAMI trial series is investigating subcutaneous amivantamab in a variety of cancers, including recurrent or metastatic head and neck squamous cell carcinoma (HNSCC).

The phase 1b/2 OrigAMI-4 trial evaluated amivantamab monotherapy in patients with human papillomavirus (HPV)–unrelated recurrent or metastatic HNSCC who progressed on immunotherapy plus chemotherapy. Over a median follow-up of 9 months, amivantamab had an objective response rate of 47% (85% CI, 37-57) and median progression-free survival of 6.8 months (95% CI, 5.2-8.2), according to data presented at ASCO 2026. These data compare very favorably against historical outcomes with cetuximab, and may support off-label use of amivantamab, said Dr. Sun.

Separately, the ongoing phase 3 OrigAMI-5 study is investigating first-line treatment with amivantamab plus pembrolizumab and carboplatin versus standard pembrolizumab plus 5-fluorouracil and carboplatin or cisplatin in patients with HPV-unrelated recurrent or metastatic HNSCC. Data are not expected for some time, but OrigAMI-5 and separate trials on petosemtamab and ficerafusp alfa may introduce EGFR-based bispecific antibodies as treatment options for head and neck cancers in the future, said Dr. Sun. 

If multiple bispecific antibody combinations are approved for head and neck cancer, oncologists will need to weigh different efficacy and safety profiles to individualize treatment for patients with head and neck cancers. Different enrollment criteria across bispecific antibody trials may also impact selection in eventual real-world practice.