FDA Approves Amivantamab for Recurrent or Metastatic HNSCC

The US Food and Drug Administration (FDA) has granted accelerated approval to subcutaneous amivantamab and hyaluronidase-lpuj (Rybrevant Faspro) for adults with recurrent or metastatic head and neck squamous cell carcinoma (HNSCC) whose disease has progressed on or after platinum-based chemotherapy and immunotherapy. It is the first drug approved in 10 years for patients with recurrent or metastatic HNSCC who have had prior platinum-based chemotherapy. The approval gives patients a new option in an aggressive, life-threatening disease where they have had few effective choices after standard treatment fails. The approval does not cover patients with oropharyngeal squamous cell carcinoma associated with human papillomavirus (HPV).

A High Unmet Need

According to the American Cancer Society, an estimated 60,480 new cases of oral cavity and pharynx cancers will be diagnosed in the United States in 2026, and about 13,150 people will die of them. HNSCC is the most common form of head and neck cancer, which can arise in the mouth, throat, voice box, sinuses, nasal cavity and salivary glands. Patients whose disease returns or spreads after immunotherapy and chemotherapy have historically had poor outcomes. Currently approved therapies produce response rates of about 20% or less in this setting.

How Amivantamab Works

Amivantamab is a bispecific antibody that targets both the epidermal growth factor receptor (EGFR) and the MET receptor. HPV-unrelated HNSCC often shows high EGFR expression and MET pathway overexpression, both of which drive tumor growth. By blocking both pathways at once, amivantamab is designed to interrupt the signals that help cancer cells grow and survive. The subcutaneous formulation combines amivantamab with hyaluronidase, which allows it to be given as an injection under the skin rather than as an intravenous infusion. Rybrevant Faspro is already approved for certain patients with EGFR-mutated non-small cell lung cancer.

Trial Results

The approval was based on cohort 1 of the open-label, multicenter phase 1b/2 OrigAMI-4 trial, which included 102 patients with recurrent or metastatic HNSCC. The overall response rate was 42%, meaning these patients’ tumors shrank or disappeared. That is more than double the rate seen with currently approved therapies. Of the patients who responded, 56% had a response lasting 6 months or longer.

Angelo De Claro, MD, director of the FDA’s Oncology Center of Excellence, said in a news release that the approval “represents a meaningful step forward for patients with head and neck squamous cell carcinoma.” He added that the therapy gives patients and their physicians a new option that could make a real difference in people’s lives.

Accelerated Approval and Confirmatory Studies

The FDA granted Rybrevant Faspro Breakthrough Therapy designation for this indication. Because the approval falls under the Accelerated Approval Program and was based on overall response rate and duration of response, the FDA requires confirmatory studies to show whether those results translate into long-term clinical benefit.

Nursing Considerations

For oncology nurses, the approval brings new responsibilities in administration, patient education and toxicity monitoring. Because Rybrevant Faspro is given as a subcutaneous injection in the clinic, nurses play a central role in watching for reactions during and after each dose and in helping patients recognize side effects between visits.

The prescribing information for single-agent use includes warnings and precautions for hypersensitivity and administration-related reactions, interstitial lung disease (ILD)/pneumonitis, dermatologic adverse reactions, ocular toxicity and embryo-fetal toxicity. Oncology nurses should take an active role in managing these risks:

Hypersensitivity and administration-related reactions: Give premedications as prescribed. Monitor patients closely during and after injections, particularly early in treatment, and be ready to intervene if symptoms appear.

ILD/pneumonitis: Assess for new or worsening cough, shortness of breath or fever at each visit. Teach patients to report respiratory symptoms right away, because ILD can be severe.

Dermatologic reactions: Educate patients on daily skin care, including alcohol-free moisturizers and sun protection. Monitor for rash, dry skin and itching so they can be managed early.

Ocular toxicity: Ask about eye pain, redness, blurred vision or other vision changes, and help arrange an ophthalmology referral when needed.

Embryo-fetal toxicity: Counsel patients of reproductive potential about the risk to an unborn baby and the need for effective contraception, as directed in the prescribing information.

Looking Ahead

Nurses should also be aware that the manufacturer is studying subcutaneous amivantamab in additional HNSCC settings, including a phase 3 trial. This research may shape how the drug is used in the future and is relevant for patients who are considering clinical trial participation.

References

1. FDA Grants Accelerated Approval to a New Treatment for Head and Neck Squamous Cell Carcinoma. FDA News Release. Silver Spring, MD: US Food and Drug Administration; November 5, 2026. Accessed November 6, 2026. [URL]
2. Burtness B, Rosenberg AJ, Calderon B, et al. Amivantamab in recurrent/metastatic head and neck squamous cell carcinoma after checkpoint inhibitor and chemotherapy: pivotal results from the phase 1b/2 OrigAMI-4 study. J Clin Oncol. Published online May 31, 2026. doi:10.1200/JCO-26-01042
3. American Cancer Society. Cancer Facts & Figures 2026. Atlanta: American Cancer Society; 2026.