After a 10-year gap, FDA approves new option for pretreated head and neck cancer

For a decade, no new drug was approved for adults with recurrent or metastatic head and neck cancer whose disease kept growing after platinum-based chemotherapy. That changed last week, when the FDA granted accelerated approval to Rybrevant Faspro (amivantamab and hyaluronidase-lpuj), according to the agency.

The under-the-skin injection from Johnson & Johnson (J&J) is approved as a single agent for adults with recurrent or metastatic head and neck squamous cell carcinoma (HNSCC) that has progressed on or after platinum-based chemotherapy and an anti-PD-(L)1 antibody, a type of immunotherapy.

It’s not approved for cancers of the oropharynx, the middle part of the throat, that are linked to human papillomavirus (HPV) based on p16 testing, J&J said in a news release. The company said this is the first therapy in this setting to target both EGFR and MET and the first approval for Rybrevant Faspro outside of non-small cell lung cancer (NSCLC).

“Today’s approval represents a meaningful step forward for patients with head and neck squamous cell carcinoma, a disease where treatment options have historically been limited and outcomes remain poor," Angelo De Claro, M.D., director of the FDA’s Oncology Center of Excellence, said in the release.

HNSCC is considered a group of malignancies involving the oral cavity, pharynx, hypopharynx, larynx, nasal cavity and salivary glands that together make the seventh most common cancer diagnosis worldwide. With 890,000 new cases and 450,000 deaths annually, according to a 2023 review by the Medical Sciences journal, HNSCC accounts for roughly 4.5% of cancer diagnoses and deaths.

How Rybrevant Faspro targets head and neck cancer

Amivantamab is a bispecific antibody, meaning it binds two targets at once. It blocks EGFR and MET, two proteins that help tumors grow. According to J&J, both are overexpressed in 80% to 90% of recurrent or metastatic HNSCC tumors and are often tied to a poorer outlook. The company said the drug also helps direct immune cells against the cancer.

The Faspro version pairs amivantamab with Halozyme’s hyaluronidase delivery technology. That lets it be given as a roughly five-minute injection rather than an IV infusion. The IV form, Rybrevant (amivantamab-vmjw), and Rybrevant Faspro are already approved for certain patients with EGFR-mutated NSCLC.

What the OrigAMI-4 trial found

The approval is based on the first cohort of OrigAMI-4, an ongoing phase 1b/2 trial. It enrolled 102 adults whose HNSCC had progressed after platinum chemotherapy and immunotherapy; patients with HPV-positive oropharyngeal cancer were excluded. Patients received a weight-based dose every three weeks until their cancer progressed or side effects became too much to manage. Results were presented at the 2026 American Society of Clinical Oncology Annual Meeting and published in the Journal of Clinical Oncology.

Tumors shrank or disappeared in 42% of patients, based on blinded independent central review. That included complete responses in 15%, or about one-third of all responders. Among patients who responded, 56% kept that response for six months or longer. The FDA noted that currently approved therapies in this setting have response rates of around 20% or less.

Those are early measures. The FDA said it’s not yet confirmed whether the response rates will translate into longer survival or other long-term benefits, which is why it required confirmatory studies. J&J’s release didn’t report progression-free or overall survival data.

“Outcomes remain poor for patients whose head and neck cancer progresses, and treatment options are limited,” Barbara Burtness, M.D., medical oncologist and professor of medicine at Yale Cancer Center, said in J&J’s release. Burtness has served as a consultant to J&J.

Side effects and first-dose monitoring

Rash was the most common side effect, affecting 79% of patients in the trial. Fatigue (39%), nail problems (35%), mouth sores (32%) and swelling (28%) were also common. Serious adverse reactions occurred in 39% of patients, and 6% had fatal adverse reactions.

The label includes warnings for hypersensitivity and administration-related reactions, lung inflammation, skin reactions, eye problems and harm to a developing fetus. Patients need premedication before dosing. After the first dose, they should be monitored for two to four hours in a setting with resuscitation equipment on hand.

What the approval means for payers

Due to the approval being accelerated, the indication’s future depends on more data. J&J said continued approval may be contingent on results from the phase 3 OrigAMI-5 trial, which is testing subcutaneous amivantamab with carboplatin and Keytruda (pembrolizumab) as a first-line treatment for recurrent or metastatic head and neck cancer.

Eligibility also relies on testing, as oropharyngeal tumors will need HPV status confirmed by p16 testing before patients qualify. According to J&J, about 80% of recurrent or metastatic HNSCC cases are not driven by HPV, and those cancers typically have a poorer prognosis. For eligible patients, the drug may be given every three or four weeks. J&J’s release did not include pricing.

Additionally, the broader patient pool is sizable. For example, the American Cancer Society (ACS) estimates about 60,480 new cases of oral cavity or oropharyngeal cancer and about 13,150 deaths from these cancers in the United States in 2026.

“At a time when treatment advances are urgently needed to improve outcomes for patients, this new option offers renewed hope for patients and their families," Amanda Hollinger, executive director of the Head and Neck Cancer Alliance, said in J&J’s release.