The U.S. Food and Drug Administration (FDA) has granted accelerated approval to Johnson & Johnson’s RYBREVANT FASPRO (amivantamab and hyaluronidase) 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-PD-(L)1 antibody. The company announced the approval. The indication does not include patients with HPV-associated oropharyngeal squamous cell carcinoma. It is the first approval of a dual-targeted therapy in this setting, simultaneously targeting epidermal growth factor receptor (EGFR) and mesenchymal-epithelial transition (MET).
The approval follows a Breakthrough Therapy Designation in February 2026 and a Priority Review designation in July 2026. It is based on clinically meaningful and durable tumour responses in the Phase 1b/2 OrigAMI-4 trial. Confirmed overall response rate was 42 percent (95 percent confidence interval 32 to 52 percent), including complete responses in 15 percent of patients – one-third of all responders – and partial responses in 28 percent, per blinded independent central review. Fifty-six percent of responders maintained a response for more than six months. Continued approval may be contingent on verification and description of clinical benefit in the ongoing confirmatory Phase 3 OrigAMI-5 trial in first-line HNSCC.
RYBREVANT FASPRO is contraindicated in patients with known hypersensitivity to hyaluronidase or any of its excipients. Warnings and precautions include hypersensitivity and administration-related reactions, interstitial lung disease (ILD)/pneumonitis, dermatologic adverse reactions, ocular toxicity and embryo-fetal toxicity. EGFR and MET are key drivers of tumour progression and are overexpressed in 80 to 90 percent of recurrent and metastatic HNSCC tumours, often associated with poor prognosis, according to the company. RYBREVANT FASPRO targets both pathways simultaneously while activating immune-cell directing activity and is delivered as a five-minute subcutaneous injection. It marks the first indication beyond non-small cell lung cancer (NSCLC) for RYBREVANT FASPRO.
„For people living with recurrent or metastatic head and neck cancer, the stakes are incredibly high. When the disease progresses, patients often face limited treatment options,“ said Amanda Hollinger, Executive Director of the Head and Neck Cancer Alliance. Barbara Burtness of Yale Cancer Center said the OrigAMI-4 findings represent important progress and highlight the potential of dual EGFR- and MET-targeting with amivantamab as a distinct treatment approach. Yusri Elsayed, Global Therapeutic Head, Oncology at Johnson & Johnson, said RYBREVANT FASPRO delivers a differentiated approach targeting both EGFR and MET to address the biology driving the disease; having redefined outcomes in EGFR+ NSCLC, the company is now unlocking the next chapter of this treatment.
In the OrigAMI-4 trial, the safety profile of RYBREVANT FASPRO was consistent with the established profile of prior amivantamab experience; no new safety signals were identified. The most common adverse reactions in at least 20 percent of patients were rash (79 percent), fatigue (39 percent), nail toxicity (35 percent), stomatitis (32 percent) and edema (28 percent). Serious adverse reactions occurred in 39 percent of patients, including pneumonia (8 percent), hemorrhage (4.9 percent), dysphagia and pneumothorax (2.9 percent each). Fatal adverse reactions occurred in 6 percent of patients who received RYBREVANT FASPRO. HNSCC represents approximately 4.5 percent of all cancers worldwide and is the seventh most common cancer globally; about 80 percent of recurrent or metastatic HNSCC are not driven by HPV and are typically associated with poorer prognosis and reduced response to treatment.
