FDA Approves Amivantamab and Hyaluronidase for Previously Treated Head and Neck Squamous Cell Carcinoma

Clinical Summary: 

• Regulatory Update: The FDA has granted accelerated approval to amivantamab and hyaluronidase (Rybrevant Faspro) as monotherapy for adults with recurrent or metastatic head and neck squamous cell carcinoma whose disease progressed on or after platinum-based chemotherapy and anti-PD-L1 therapy. The indication excludes HPV-associated oropharyngeal squamous cell carcinoma.

• Key Outcomes: The approval was supported by results from Cohort 1 of the phase 1b/2 OrigAMI-4 trial, in which subcutaneous amivantamab demonstrated a confirmed objective response rate of 42%, including complete responses in 15% of patients. Among responders, 56% maintained a response for more than 6 months.

• Clinical Relevance: This approval introduces a subcutaneous, dual EGFR/MET-targeted treatment option for eligible patients with previously treated recurrent or metastatic head and neck squamous cell carcinoma. Continued approval may depend on confirmation of clinical benefit in the ongoing phase 3 OrigAMI-5 trial.

On November 5, 2026, the US Food and Drug Administration (FDA) granted accelerated approval to amivantamab and hyaluronidase (Rybrevant Faspro; Johnson & Johnson) as a single agent for adults with recurrent or metastatic head and neck squamous cell carcinoma whose disease has progressed on or after platinum-based chemotherapy and an anti-PD-L1 antibody, introducing a subcutaneous, dual EGFR/MET-targeted treatment option in this setting.

The indication excludes patients with human papillomavirus (HPV)-associated oropharyngeal squamous cell carcinoma, as determined by p16 immunohistochemistry.

The approval was supported by findings from Cohort 1 of the ongoing phase 1b/2 OrigAMI-4 trial, which enrolled 102 adults whose disease had progressed on or after platinum-based chemotherapy and anti-PD-L1 therapy, excluding patients with HPV-associated oropharyngeal squamous cell carcinoma. Patients received weight-based subcutaneous amivantamab every 3 weeks at the recommended dose and schedule until disease progression or unacceptable toxicity.

The primary end point was objective response rate (ORR). Key secondary end points included duration of response and safety. End points were assessed by blinded independent central review according to RECIST version 1.1.

At analysis, the confirmed ORR was 42%, including complete responses in 15% of patients and partial responses in 28%. Among patients who achieved a response, 56% maintained their response for more than 6 months. The reported duration of response range was 1.4+ to 19.7+ months.

The safety profile of subcutaneous amivantamab was reported to be consistent with previous amivantamab experience, with no new safety signals identified. The most common adverse reactions were rash (79%), fatigue (39%), nail toxicity (35%), stomatitis (32%), and edema (28%).

Serious adverse reactions occurred in 39% of patients. The most frequently reported serious adverse reactions included pneumonia (8%), hemorrhage (4.9%), dysphagia (2.9%), and pneumothorax (2.9%). Fatal adverse reactions occurred in 6% of patients, including sudden death (2%), myocardial ischemia, tumor hemorrhage, aspiration pneumonia, and interstitial lung disease/pneumonitis (1% each). 

The prescribing information includes warnings and precautions for hypersensitivity and administration-related reactions, interstitial lung disease/pneumonitis, dermatologic adverse reactions, ocular toxicity, and embryo-fetal toxicity.

The approval represents the first indication for Rybrevant Faspro beyond non-small cell lung cancer and introduces a dual EGFR/MET-targeted treatment approach for eligible patients with recurrent or metastatic head and neck squamous cell carcinoma. 

Continued approval may be contingent upon verification of clinical benefit in the ongoing phase 3 OrigAMI-5 trial, which is evaluating subcutaneous amivantamab plus carboplatin and pembrolizumab as first-line treatment for recurrent or metastatic head and neck squamous cell carcinoma.

Source: 

Johnson & Johnson. Johnson & Johnson announces US FDA approval of RYBREVANT FASPRO™ (amivantamab and hyaluronidase-lpuj) as first and only dual-targeted therapy for advanced head and neck cancer. Accessed on: November 5, 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