FDA Approves Rybrevant Faspro for Advanced Head and Neck Cancer

The Food and Drug Administration (FDA) on Nov. 5, 2026, granted accelerated approval to Rybrevant Faspro (amivantamab and hyaluronidase-lpuj) as a single treatment for adults with recurrent or metastatic head and neck squamous cell carcinoma (HNSCC) whose disease grew during or after platinum-based chemotherapy and an immunotherapy drug known as a PD-1 or PD-L1 inhibitor.

HNSCC is the most common type of head and neck cancer. It starts in the thin, flat cells that line the mouth, throat and voice box. "Recurrent" means the cancer came back after treatment, and "metastatic" means it has spread to other parts of the body.

The approval does not include people with HPV-associated oropharyngeal squamous cell carcinoma. That is cancer in the back of the throat caused by the human papillomavirus (HPV), and it is identified with a lab test called p16 immunohistochemistry.

Rybrevant Faspro is injected under the skin (subcutaneously). It targets two proteins, EGFR and MET, that can help cancer cells grow. These proteins are found at high levels in most recurrent or metastatic head and neck tumors, according to Johnson & Johnson, which makes the drug. Rybrevant Faspro was previously approved for certain people with EGFR-mutated non-small cell lung cancer. This is its first approval outside of lung cancer.

How Well Did Rybrevant Faspro Shrink Head and Neck Tumors?

In the phase 1b/2 OrigAMI-4 trial, 42% of patients treated with Rybrevant Faspro had their tumors shrink or disappear, a measure called the overall response rate. Fifteen percent of patients had a complete response, meaning no remaining signs of cancer on scans. These patients made up about one-third of everyone who responded.

Among patients whose tumors responded, 56% kept their response for more than six months.

"The meaningful responses observed in this study are encouraging for patients," Dr. Barbara Burtness, a medical oncologist and professor of medicine at Yale Cancer Center in New Haven, Connecticut, said in a Johnson & Johnson news release. Burtness has served as a consultant to Johnson & Johnson.

Amanda Hollinger, executive director of the Head and Neck Cancer Alliance, said in the release that "this new option offers renewed hope for patients and their families."

Who Was Included in the OrigAMI-4 Clinical Trial?

The open-label trial, in which patients and doctors knew which treatment was given, included 102 adults with recurrent or metastatic HNSCC that had already been treated with platinum-based chemotherapy and a PD-1 or PD-L1 inhibitor. People with HPV-associated cancer of the back of the throat were not included.

Patients received Rybrevant Faspro at a weight-based dose every three weeks, after a first loading dose, until their cancer grew or side effects became too hard to manage. Tumor responses were confirmed by independent reviewers who did not know which patients they were assessing.

Because this is an accelerated approval based on how often and how long tumors responded, continued approval may depend on results from a confirmatory trial. That trial, the phase 3 OrigAMI-5 study, is testing Rybrevant Faspro with the chemotherapy carboplatin and the immunotherapy Keytruda (pembrolizumab) as a first treatment for recurrent or metastatic head and neck cancer.

What Are the Side Effects and Risks of Rybrevant Faspro?

The most common side effects, seen in at least 20% of patients in the trial, were:

• Rash (79%)
• Fatigue (39%)
• Nail problems (35%)
• Mouth sores, or stomatitis (32%)
• Swelling, or edema (28%)

Serious side effects occurred in 39% of patients. The most common were pneumonia (8%) and bleeding (4.9%). Side effects led to death in 6% of patients, including sudden death (2%), as well as reduced blood flow to the heart, tumor bleeding, pneumonia from inhaling food or liquid, and lung inflammation (one patient each).

The prescribing information includes warnings for:

• Allergic reactions and reactions to the injection
• Interstitial lung disease or pneumonitis, which is inflammation of the lungs
• Skin reactions
• Eye problems
• Harm to an unborn baby

People who should not receive Rybrevant Faspro include anyone with a known allergy to hyaluronidase or any of the drug's other ingredients.

What Patients Should Know Before Starting Treatment

Before each injection, patients are given medicines, including an antihistamine, a fever reducer and a steroid, to lower the risk of a reaction. Skin problems are very common with this treatment, so patients should ask their care team about skin care, sun protection and medicines that can help prevent a rash. Patients should tell their care team right away about a new or worsening cough, shortness of breath, eye changes or skin reactions.

References

1. "FDA grants accelerated approval to amivantamab and hyaluronidase-lpuj for recurrent or metastatic head and neck squamous cell carcinoma." News Release. U.S. Food and Drug Administration. Nov. 5, 2026.
2. "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." Johnson & Johnson. Nov. 5, 2026.

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