FDA Approves Rybrevant Faspro for Advanced Head and Neck Cancer

The 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 whose disease progressed during or after platinum-based chemotherapy and a PD-1 or PD-L1 inhibitor. The subcutaneously injected bispecific antibody targets EGFR and MET proteins, which are found at high levels in most recurrent or metastatic head and neck tumors.

The company reported that 15% of patients achieved a complete response, meaning no detectable cancer remained. Among those who responded, 56% maintained their response for more than six months, and 7% had responses lasting at least a year, according to trial results cited by Healio and CURE. Tumor responses were confirmed by independent reviewers who were blinded to the patient assessments, records show.

In the phase 1b/2 OrigAMI-4 clinical trial, 42% of the 102 participating patients saw their tumors shrink or disappear, according to data from Johnson & Johnson, the drug’s manufacturer.

The trial enrolled adults with recurrent or metastatic head and neck squamous cell carcinoma whose disease progressed during or after treatment with both platinum-based chemotherapy and a PD-1 or PD-L1 inhibitor. Researchers noted that historical data show patients with prior chemotherapy have a 10% to 12% overall response rate to single-agent cetuximab or paclitaxel, while those previously treated with immune checkpoint inhibitors have a response rate between 21% and 24%, according to Healio.

The approval excludes patients with HPV-associated oropharyngeal squamous cell carcinoma, identified through p16 immunohistochemistry testing, according to CURE. The approved dose is 160 mg/2,000 units per mL, according to Healio.

Safety data from the trial showed that the most common side effects, occurring in at least 20% of patients, included rash (79%), fatigue (35%), nail toxicity (35%), stomatitis (32%) and edema (28%), according to Healio. Serious side effects occurred in 39% of patients, with the most common being pneumonia (8%) and bleeding (4.9%), according to CURE. 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, each occurring in one patient, records show.

The drug is a bispecific antibody that targets EGFR and MET proteins, which are found at high levels in most recurrent or metastatic head and neck tumors, according to CURE. Blocking both proteins is intended to overcome drug resistance that can develop when only one target is hit, according to MedCity News. The subcutaneous formulation uses technology from Halozyme that allows for injection in about five minutes, compared with two to five hours for the IV-infused version of Rybrevant, according to MedCity News.

The IV-infused Rybrevant was initially approved in 2021 for EGFR-mutated non-small cell lung cancer. In 2024, the FDA approved Lazcluze in combination with Rybrevant for improved EGFR coverage, according to MedCity News. The FDA’s approval of Rybrevant Faspro in December 2025 covered all indications at that time for the IV-infused version, records show.

Dr. Barbara Burtness, a medical oncologist and professor of medicine at Yale Cancer Center who has served as a consultant to Johnson & Johnson, said in a company news release: “The meaningful responses observed in this study are encouraging for patients.” Amanda Hollinger, executive director of the Head and Neck Cancer Alliance, said in the release: “This new option offers renewed hope for patients and their families.”

Because the approval is accelerated, based on how often and how long tumors responded, continued approval may depend on results from a confirmatory trial, according to CURE. The phase 3 OrigAMI-5 study is testing Rybrevant Faspro in combination with the chemotherapy carboplatin and the immunotherapy Keytruda (pembrolizumab) as a first-line treatment for recurrent or metastatic head and neck cancer, according to CURE. That trial could support expansion of the drug to first-line treatment, according to MedCity News.

For the first nine months of 2026, Johnson & Johnson reported $866 million in global Rybrevant/Lazcluze sales, a 67.4% increase compared with the same period in the prior year, according to MedCity News. The company has previously projected Rybrevant could reach $5 billion in peak sales.