FDA Approves Rybrevant Faspro for Advanced Head and Neck Cancer

FDA has granted accelerated approval to amivantamab and hyaluronidase-lpuj (Rybrevant Faspro) as a single agent for adults with recurrent or metastatic head and neck squamous cell carcinoma (HNSCC) whose disease has progressed on or after platinum-based chemotherapy and an anti-programmed cell death protein (ligand) 1 (PD-[L]1) antibody, Johnson & Johnson announced on November 5, 2026.¹

The subcutaneous therapy is the first dual-targeted treatment approved in this setting, simultaneously targeting the epidermal growth factor receptor (EGFR) and mesenchymal-epithelial transition (MET) pathways, according to the company.¹ The indication excludes patients with HPV-associated oropharyngeal squamous cell carcinoma (OPSCC).¹

"The OrigAMI-4 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," said Barbara Burtness, MD, medical oncologist and professor of medicine at Yale Cancer Center, in a company press release.¹

What did the OrigAMI-4 trial show?

The approval is based on cohort 1 of the phase 1b/2 OrigAMI-4 trial, which evaluated amivantamab as a single agent in 102 adults with previously treated recurrent or metastatic HNSCC, excluding those with HPV-associated OPSCC.¹,² By blinded independent central review, the confirmed overall response rate was 42% (95% confidence interval, 32%-52%), including complete responses in 15% of patients and partial responses in 28%.¹ Among responders, 56% maintained a response for more than 6 months.¹ The pivotal results were presented at the 2026 American Society of Clinical Oncology Annual Meeting and published in the Journal of Clinical Oncology.²

The approval followed FDA breakthrough therapy designation in February 2026 and priority review in July 2026.¹ According to Johnson & Johnson, it is the first advancement in the second-line treatment setting for recurrent or metastatic head and neck cancer in a decade.¹

How does amivantamab work?

Amivantamab is a fully human bispecific antibody that targets EGFR and MET with immune cell-directing activity.¹ According to the company, EGFR and MET are overexpressed in 80% to 90% of recurrent and metastatic HNSCC tumors and are associated with poor prognosis.¹ Rybrevant Faspro is co-formulated with recombinant human hyaluronidase and is administered as a subcutaneous injection; the approval marks the therapy's first indication beyond non-small cell lung cancer, where amivantamab-based regimens are approved for EGFR-mutated disease.¹

Why does this matter for head and neck cancer?

HNSCC is the most common form of head and neck cancer and the seventh most common cancer globally, according to the company.¹ Roughly 80% of recurrent or metastatic HNSCC cases are not driven by HPV and are typically associated with poorer prognosis.¹ Many patients progress to advanced disease despite surgery, radiation, chemotherapy, and immunotherapy, and few new options have reached the second-line setting.¹

What is the safety profile?

The most common adverse reactions, occurring in at least 20% of patients, were rash (79%), fatigue (39%), nail toxicity (35%), stomatitis (32%), and edema (28%).¹ Serious adverse reactions occurred in 39% of patients, and fatal adverse reactions occurred in 6%, including sudden death in 2%.¹ The prescribing information includes warnings for hypersensitivity and administration-related reactions, interstitial lung disease/pneumonitis, dermatologic and ocular toxicity, and embryo-fetal toxicity.¹ Johnson & Johnson said no new safety signals were identified.¹

What are the limitations?

The accelerated approval is based on overall response rate and duration of response, which are surrogate measures, rather than survival. Continued approval may be contingent on verification of clinical benefit in the confirmatory phase 3 OrigAMI-5 trial (NCT07276399), which is evaluating subcutaneous amivantamab with carboplatin and pembrolizumab as a first-line treatment.¹^,³ The pivotal cohort was single-arm and included 102 patients without a comparator. The indication does not cover HPV-associated OPSCC, and serious and fatal adverse reactions were reported.

References

1. Johnson & Johnson. 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. Press release. Published 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
2. Burtness B, Rosenberg AJ, Calderon B, et al. Amivantamab in recurrent/metastatic head and neck squamous cell cancer after checkpoint inhibitor and chemotherapy: pivotal results from the phase Ib/II OrigAMI-4 study. J Clin Oncol. 2026;44(24):2271-2277. doi:10.1200/JCO-26-01042
3. A study of amivantamab in addition to standard of care agents (SOC) compared with SOC alone in participants with recurrent/metastatic head and neck cancer (OrigAMI-5). ClinicalTrials.gov; NCT07276399. Updated November 3, 2026. Accessed November 6, 2026. https://clinicaltrials.gov/study/NCT07276399