FDA has granted priority review to Johnson & Johnson's supplemental biologics license application (sBLA) for subcutaneous amivantamab and hyaluronidase-lpuj (Rybrevant Faspro) in adults with recurrent or metastatic head and neck squamous cell carcinoma (HNSCC) whose disease has progressed after platinum-based chemotherapy and a programmed cell death protein 1 (PD-1) or programmed dell death ligand 1 (PD-L1) inhibitor. Priority review is granted to therapies that may offer significant improvements in safety or effectiveness for serious conditions and shortens FDA's review timeline to approximately 6 months.1,2
"One of the hardest things about advanced head and neck cancer is that it can impact our most basic functions, like the ability to speak, eat, and even breathe easily, profoundly affecting patients' daily lives," said Yusri Elsayed, MD, MHSc, PhD, global therapeutic area head, oncology, at Johnson & Johnson, in a company press release.1 "Building on the established role of subcutaneous amivantamab in lung cancer, this milestone underscores its continued potential across multiple tumor types."
Key facts
- Drug: Amivantamab + hyaluronidase-lpuj (Rybrevant Faspro)
- Status: FDA priority review granted (sBLA)
- Trial: OrigAMI-4 phase 1b/2, cohort 1, NCT06385080
- Efficacy: 42% ORR, >1/3 of responders with CR
What clinical data support the priority review?
The priority review is supported by pivotal results from the phase 1b/2 OrigAMI-4 study, in which 42% of patients with recurrent or metastatic (R/M) HNSCC responded to monotherapy subcutaneous amivantamab, with more than 1/3 of responders achieving a complete response.1 The study excluded patients with human papillomavirus (HPV)-positive oropharyngeal squamous cell carcinoma and those who had received prior anti-epidermal growth factor receptor (EGFR) therapy. The findings were presented at the 2026 American Society of Clinical Oncology annual meeting and published simultaneously in the Journal of Clinical Oncology.1,3
OrigAMI-4 (NCT06385080) is an open-label, 6-cohort study. Cohort 1, which supported this application, evaluated subcutaneous amivantamab as monotherapy in patients previously treated with platinum-based chemotherapy and a PD-1/PD-L1 inhibitor.1 Amivantamab was dosed weekly during the initial treatment period, then every 3 weeks with weight-based adjustments, and the primary endpoint across cohorts is overall response rate by investigator assessment using RECIST v1.1.1
What is the disease burden of HNSCC?
HNSCC represents approximately 4.5% of all cancers worldwide and is the 7th most common cancer globally; major risk factors include tobacco and alcohol use and high-risk HPV infection.1,4 Roughly 80% of recurrent or metastatic HNSCC is not HPV-driven and is typically associated with a poorer prognosis and reduced treatment response; despite advances in surgery, radiation, chemotherapy, and immunotherapy, many patients progress to advanced recurrent or metastatic disease, where 5-year survival is only 15%.1
How does amivantamab work, and what is its regulatory history?
Amivantamab is a fully human bispecific antibody that targets EGFR and mesenchymal-epithelial transition (MET), both implicated in tumor progression and treatment resistance and overexpressed in 80% to 90% of HNSCC tumors, while also engaging the immune system.1 Subcutaneous amivantamab and hyaluronidase-lpuj is co-formulated with recombinant human hyaluronidase PH20 (rHuPH20), Halozyme's Enhanze drug delivery technology, and received its first FDA approval in December 2025 for EGFR-mutated non-small cell lung cancer (NSCLC), where it is approved in more than 40 countries as the only subcutaneous therapy for these EGFR-mutated NSCLC populations.1 The intravenous formulation's effectiveness is supported by phase 3 MARIPOSA data showing improved progression-free and overall survival when combined with lazertinib (Lazcluze) in first-line EGFR-mutated NSCLC.1
What are the limitations and what comes next?
OrigAMI-4's cohort 1 data come from a single-arm, open-label study without a randomized comparator, and the population studied excluded HPV-positive oropharyngeal cancer and prior anti-EGFR-treated patients, meaning results may not generalize to the full R/M HNSCC population. Priority review designation does not guarantee approval, and FDA's final decision remains pending.
References
- Johnson & Johnson. Johnson & Johnson's Rybrevant Faspro (amivantamab and hyaluronidase-ipuj) receives US FDA priority review as potential first-in-class EGFR- and MET-targeted subcutaneous treatment for advanced head and neck cancer. Press release. Published July 30, 2026. Accessed July 30, 2026. https://www.jnj.com/media-center/press-releases/johnson-johnsons-rybrevant-faspro-amivantamab-and-hyaluronidase-lpuj-receives-u-s-fda-priority-review-as-potential-first-in-class-egfr-and-met-targeted-subcutaneous-treatment-for-advanced-head-and-neck-cancer
- FDA. Priority Review. Accessed July 2026. https://www.fda.gov/patients/fast-track-breakthrough-therapy-accelerated-approval-priority-review/priority-review
- 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. May 31, 2026. doi:10.1200/JCO-26-01042
- 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