J&J's Rybrevant Faspro Receives FDA Breakthrough Therapy Designation for Head and Neck Cancer

The U.S. Food and Drug Administration has granted Breakthrough Therapy Designation for subcutaneous amivantamab and hyaluronidase-lpuj as a monotherapy for the treatment of adults with head and neck squamous cell carcinoma that is recurrent or metastatic and human papillomavirus (HPV)-unrelated after disease progression on or after platinum-based chemotherapy and a PD-1 or PD-L1 inhibitor. The designation is based on data showing rapid and durable responses in a heavily pretreated patient population and expands the promise of RYBREVANT FASPRO™ beyond lung cancer.

The designation is supported by data from the open-label Phase 1b/2 OrigAMI-4 study. Results were presented in a mini-oral session at the 2025 European Society for Medical Oncology (ESMO) Congress and demonstrate promising clinical activity, with rapid and durable responses, in a heavily pretreated patient population.

HPV-unrelated recurrent or metastatic head and neck squamous cell carcinoma is characterized by high rates of epidermal growth factor receptor (EGFR) expression and mesenchymal-epithelial transition (MET) pathway overexpression. Subcutaneous amivantamab is designed to target both pathways, while activating the immune system. The clinical activity observed to date supports further evaluation in this setting, where treatment options remain limited after prior lines of therapy.

Based on these findings, subcutaneous amivantamab is being further evaluated in the ongoing Phase 3 OrigAMI-5 study (NCT07276399), which is assessing the subcutaneous formulation of amivantamab in combination with pembrolizumab and carboplatin versus 5-fluorouracil (5FU) plus pembrolizumab and platinum-based chemotherapy (cisplatin or carboplatin) as a first-line treatment in patients with HPV-unrelated recurrent or metastatic head and neck squamous cell carcinoma, regardless of PD-L1 expression.

The FDA grants Breakthrough Therapy Designation to expedite the development and regulatory review of investigational medicines intended to treat serious or life-threatening conditions, where preliminary clinical evidence indicates the therapy may demonstrate substantial improvement over available treatment options on at least one clinically meaningful endpoint.

RYBREVANT FASPRO™ is approved in multiple settings for the treatment of locally advanced or metastatic non-small cell lung cancer and is also being evaluated in additional solid tumors, including colorectal cancer. In December 2025, the U.S. FDA approved RYBREVANT FASPRO™ (amivantamab and hyaluronidase-lpuj) across all indications of intravenous RYBREVANT® (amivantamab-vmjw). This subcutaneously administered therapy is also approved in Europe, Japan, China, and other markets.

Head and neck squamous cell carcinoma is the most common type of head and neck cancer, accounting for more than 90 percent of cases and approximately 4.5 percent of all cancers worldwide. It develops in the mucosal linings of the oral cavity, oropharynx, hypopharynx, and larynx. Major risk factors include tobacco and alcohol use, as well as infection with high-risk human papillomavirus (HPV). Around 75 percent of cases are HPV-negative, which is typically associated with a poorer prognosis and reduced response to treatment. Despite advances in surgery, radiation, chemotherapy, and immunotherapy, many patients ultimately progress to advanced, recurrent or metastatic disease.