The FDA granted accelerated approval on Nov. 5 to Johnson & Johnson’s Rybrevant Faspro (amivantamab and hyaluronidase-lpuj) for adults with recurrent or metastatic head and neck squamous cell carcinoma whose disease has progressed on or after platinum-based chemotherapy and an immune checkpoint inhibitor.¹ The single-agent indication gives clinicians a subcutaneous option in a setting with few therapies.

The product is a bispecific antibody directed at epidermal growth factor receptor (EGFR) and mesenchymal-epithelial transition (MET) pathways, and this is its first indication outside lung cancer.¹ The label excludes patients with human papillomavirus (HPV)-associated oropharyngeal squamous cell carcinoma, and continued approval may depend on a confirmatory trial.¹

“Outcomes remain poor for patients whose head and neck cancer progresses, and treatment options are limited,” said Barbara Burtness, M.D., medical oncologist and professor of medicine at Yale Cancer Center in New Haven, Connecticut.¹

What did the OrigAMI-4 trial show in previously treated patients?

The approval rests on cohort 1 of OrigAMI-4, an open-label, multicenter phase 1b/2 study that gave single-agent amivantamab and hyaluronidase-lpuj to 102 patients who had received platinum-based chemotherapy and an immune checkpoint inhibitor. Patients with HPV-associated oropharyngeal cancer were excluded.

Participants received weight-based doses every three weeks until progression or unacceptable toxicity.¹ The primary endpoint was overall response rate (ORR) and the secondary endpoint was duration of response, both assessed by blinded independent central review.¹

Confirmed ORR was 42% (95% confidence interval, 32% to 52%), including complete responses in 15% of patients and partial responses in 28%.¹ Among responders, 56% maintained a response for more than six months.¹

Investigators reported the results in the Journal of Clinical Oncology.²

What safety findings accompany the approval?

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 6% had fatal adverse reactions, including sudden death in 2% and single cases of myocardial ischemia, tumor hemorrhage, aspiration pneumonia and interstitial lung disease.¹

The company reports no new safety signals compared with prior Rybrevant Faspro experience. The label carries warnings for hypersensitivity and administration-related reactions, interstitial lung disease, dermatologic and ocular toxicity, and embryo-fetal toxicity.¹

Why does recurrent head and neck cancer remain difficult to treat?

Head and neck squamous cell carcinoma accounts for roughly 4.5% of cancer diagnoses worldwide and ranks seventh in incidence.³ Tobacco, alcohol and high-risk HPV infection are the major risk factors.³

Johnson & Johnson estimates that about 80% of recurrent or metastatic cases are not HPV-driven and typically carry a poorer prognosis, and says EGFR and MET are overexpressed in 80% to 90% of these tumors.¹

How does Rybrevant Faspro fit the treatment landscape?

Immune checkpoint inhibitors changed care after platinum therapy. In a 2016 phase 3 trial of platinum-refractory disease, nivolumab produced median overall survival of 7.5 months versus 5.1 months with standard single-agent therapy.⁴

The new indication follows that sequence, and the company describes it as the first advance in second-line treatment in a decade.¹ FDA granted breakthrough therapy designation in February and priority review in July.¹

The subcutaneous product is co-formulated with recombinant human hyaluronidase PH20, and the company says administration takes five minutes.¹

What are the limitations and next steps?

The evidence comes from a single-arm, open-label cohort, so the response rate cannot be compared directly with other options, and the company’s announcement did not report survival outcomes. Serious and fatal adverse reaction rates also warrant consideration in a population with advanced disease.¹

Accelerated approval requires verification of clinical benefit. The designated confirmatory study, the phase 3 OrigAMI-5 trial, evaluates subcutaneous Rybrevant Faspro with carboplatin and pembrolizumab as first-line treatment, a different setting and regimen from the approved single-agent, second-line use.¹

Open questions include how responses translate to survival and how tolerability affects long-term use.

Sources

1. 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. News release. 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
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. Barsouk A, Aluru JS, Rawla P, Saginala K, Barsouk A. Epidemiology, risk factors, and prevention of head and neck squamous cell carcinoma. Med Sci (Basel). 2023;11(2):42. doi:10.3390/medsci11020042
4. Ferris RL, Blumenschein G Jr, Fayette J, et al. Nivolumab for recurrent squamous-cell carcinoma of the head and neck. N Engl J Med. 2016;375(19):1856-1867. doi:10.1056/NEJMoa1602252