Amivantamab Becomes First FDA-Approved Therapy in 10 Years for Pretreated Recurrent or Metastatic HNSCC

The FDA granted accelerated approval to amivantamab and hyaluronidase (Rybrevant Faspro; Johnson & Johnson) for adults with recurrent or metastatic head and neck squamous cell carcinoma (HNSCC), filling a treatment gap for patients who progress after both platinum chemotherapy and a checkpoint inhibitor.¹

“Outcomes remain poor for patients whose head and neck cancer progresses, and treatment options are limited,” said Barbara Burtness, MD, medical oncologist and professor of medicine at Yale Cancer Center in New Haven, Connecticut.²

“The OrigAMI-4 [NCT06385080] findings represent important progress and highlight the potential of dual EGFR- and MET-targeting with amivantamab as a distinct treatment approach in recurrent or metastatic head and neck cancer, excluding HPV-associated oropharyngeal squamous cell carcinoma,” she said. “The meaningful responses observed in this study are encouraging for patients who have long faced limited treatment options.”²

It is important to note that the approval does not indicate amivantamab and hyaluronidase for treatment of patients with oropharyngeal squamous cell carcinoma that is associated with human papillomavirus (HPV).¹

The Trial Supporting the Approval

Amivantmab hyaluronidase, a bispecific antibody targeting EGFR and MET, was examined in the multi-cohort, multicenter, open-label, ongoing Phase 1b/2 study OrigAMI-4 trial. The trial included 6 cohorts, of which the approval is based on data from the first. A total of 102 patients with HPV-unrelated recurrent/metastatic HNSCC received subcutaneous amivantamab at a dose of 1600 mg (≥ 80 kg, 2240 mg) on cycle 1 day 1, then 2400 mg (≥ 80 kg, 3360 mg) on cycle 1 day 8 and day 15, and then every 3 weeks.³

The primary end point was overall response rate (ORR), with secondary end points including duration of response (DOR), progression-free survival, and safety.³

Data from cohort 1 showed that amivantmab hyaluronidase yielded an overall response rate of 42% (95 percent CI, 32–52 percent), of whom 56% of that population had DOR lasting 6 months or longer. The ORR included a complete response rate of 15% and a partial response rate of 28%.^1,2

The safety profile of amivantamab and hyaluronidase was consistent, and no new safety signals were identified. The most common adverse reactions (≥ 20%) were rash (79%), fatigue (39%), nail toxicity (35%), stomatitis (32%), and edema (28%). Serious adverse reactions occurred in 39% of patients, most often pneumonia (8%) and hemorrhage (4.9%). Fatal adverse reactions occurred in 6% of patients, including sudden death (2%), myocardial ischemia, tumor hemorrhage, aspiration pneumonia, and ILD/pneumonitis (1% each).²

Considerations for Pharmacists

As amivantamab and hyaluronidase move into practice, pharmacists will be crucial for ensuring safe use of the agent in patients with NHSCC.

Toxicity Management

• Dermatologic toxicity: Provide early education on skin care, sun protection, and prompt reporting of paronychia.
• Stomatitis: Anticipate greater difficulty in patients with radiation-related mucositis, xerostomia, or dysphagia.
• Pneumonia and aspiration: Pneumonia was the most common serious adverse reaction, suggesting a role for proactive oral care and attention to aspiration risk.
• ILD/pneumonitis: Counsel patients to report new cough or dyspnea.
• Ocular toxicity: Flag eye symptoms for possible ophthalmology referral.
• Hemorrhage: Review anticoagulant and antiplatelet use.

Administration

• Given as a subcutaneous injection every 3 weeks with weight-based dosing, offering shorter chair time than intravenous amivantamab.
• Premedicate with an antihistamine, an antipyretic, and a glucocorticoid; interrupt the injection if a hypersensitivity or administration-related reaction is suspected.
• The agent is contraindicated in patients with known hypersensitivity to hyaluronidase or its excipients.

Continued approval may be contingent on verification of clinical benefit in a confirmatory trial, so whether this response rate translates into a survival advantage remains an open question.^1,2 Until then, pharmacists will play a central role in helping patients stay on therapy long enough to benefit, by anticipating toxicities, managing them early, and keeping a heavily pretreated population supported through treatment.

REFERENCES

1. FDA grants accelerated approval to a new treatment for head and neck squamous cell carcinoma. FDA. November 5, 2026. Accessed November 6, 2026. https://www.fda.gov/news-events/press-announcements/fda-grants-accelerated-approval-new-treatment-head-and-neck-squamous-cell-carcinoma?utm_medium=email&utm_source=govdelivery

2. Johnson & Johnson announces U.S. FDA Approval of RYBREVANT FASPRO™ (amivantamab and hyaluronidase-lpuj) as First and Only Dual-Targeted Therapy for Advanced Head and Neck Cancer. Johnson&Johnson. November 5, 2026. Accessed November 6, 2026. https://www.jnj.com/media-center/press-releases/johnson-johnson-announces-u-s-fda-approval-of-rybrevant-faspro-amivantamab-and-hyaluronidase-lpuj-as-first-and-only-dual-targeted-therapy-for-advanced-head-and-neck-cancer

3. Barbara Burtness 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. J Clin Oncol.May 27, 2026. DOI:10.1200/JCO.2026.44.16_suppl.6008