FDA Grants Accelerated Approval to Amivantamab and Hyaluronidase for Previously Treated HNSCC

The FDA granted accelerated approval on Nov. 5, 2026, to subcutaneous amivantamab and hyaluronidase-lpuj (Rybrevant Faspro) for adults with recurrent or metastatic head and neck squamous cell carcinoma who progressed on prior platinum-based chemotherapy and a PD-1/PD-L1 inhibitor. The approval, according to the agency, was based on an objective response rate of 42% from the phase 1b/2 OrigAMI-4 trial.

The approval was based on cohort 1 of the phase 1b/2 OrigAMI-4 trial (NCT06385080), which enrolled 102 patients with recurrent or metastatic HNSCC, according to Targeted Oncology. Among responders, 56% maintained a response for at least six months, with a duration range of 1.4+ to 19.7+ months.

The confirmed objective response rate by blinded independent central review was 42% (95% CI, 32%-52%), with complete responses in 15% of patients and partial responses in 28%, the trial results showed.

At a median follow-up of 11.8 months, median progression-free survival was 6.8 months, and median overall survival was 12.5 months, according to trial data. The FDA noted that currently approved therapies in this setting yield response rates of roughly 20% or lower, and this marks the first approval in 10 years for patients with recurrent or metastatic HNSCC previously treated with platinum-based chemotherapy.

The indication excludes patients with HPV-associated oropharyngeal squamous cell carcinoma, as determined by p16 immunohistochemistry, according to the agency. This is the first approval of a dual-targeted therapy in this setting, simultaneously targeting EGFR and MET, and the first approval for the subcutaneous product beyond non-small cell lung cancer, according to Johnson & Johnson.

EGFR and MET are overexpressed in 80% to 90% of recurrent or metastatic HNSCC tumors, according to Targeted Oncology. Patients in the trial received subcutaneous amivantamab at 1600 mg (2240 mg for those weighing at least 80 kg) on cycle 1 day 1, followed by 2400 mg (3360 mg for those weighing at least 80 kg) every three weeks until disease progression or unacceptable toxicity.

The median patient age was 63.5 years, 45% of patients were Asian, and 43% were White, according to trial data. Adverse reactions reported in at least 20% of patients were rash (79%), fatigue (39%), nail toxicity (35%), stomatitis (32%), and edema (28%), according to Targeted Oncology. Serious adverse reactions occurred in 39% of patients, including pneumonia (8%) and hemorrhage (4.9%). Fatal adverse reactions occurred in 6% of patients, including sudden death (2%) and one case each of myocardial ischemia, tumor hemorrhage, aspiration pneumonia, and interstitial lung disease/pneumonitis.

Administration-related reactions occurred in 13% of patients, all grade 1 or 2, and 8% discontinued because of treatment-related adverse events, according to trial results. The prescribing information includes warnings for hypersensitivity and administration-related reactions, interstitial lung disease/pneumonitis, dermatologic reactions, ocular toxicity, and embryo-fetal toxicity. The product is contraindicated in patients with known hypersensitivity to hyaluronidase or its excipients.

“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,” said Angelo De Claro, MD, director of the FDA’s Oncology Center of Excellence, in a statement.

“The meaningful responses observed in this study are encouraging for patients who have long faced limited treatment options,” said Barbara Burtness, MD, medical oncologist and professor of medicine at Yale Cancer Center.

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

The FDA previously granted breakthrough therapy designation to subcutaneous amivantamab for this indication in February 2026 and priority review in July 2026, according to Targeted Oncology. Continued approval may depend on confirmation of benefit in the ongoing phase 3 OrigAMI-5 trial (NCT07276399), which is evaluating subcutaneous amivantamab plus carboplatin and pembrolizumab as first-line treatment for recurrent or metastatic HNSCC.

The drug is co-formulated with Halozyme’s ENHANZE drug delivery technology, which uses the proprietary enzyme rHuPH20 to facilitate subcutaneous delivery, according to Halozyme Therapeutics, Inc. The company announced the approval, noting that ENHANZE has touched more than one million patient lives through ten commercialized products across over 100 global markets.