FDA Approves RYBREVANT FASPRO With a 42% Response Rate for Head and Neck Cancer

Key Facts

The U.S. Food and Drug Administration on November 5, 2026, granted accelerated approval to RYBREVANT FASPRO, a combination of amivantamab and hyaluronidase-lpuj, to treat adults with recurrent or metastatic squamous cell carcinoma of the head and neck. The indication covers patients whose disease progressed during or after platinum-based chemotherapy, as well as during or after treatment with an anti-PD-(L)1 antibody. The agency said the overall response rate in the pivotal trial was 42%, compared with a rate of about 20% or less for currently approved treatments. It also said this was the first approval in 10 years of a drug for this patient group previously treated with platinum-based therapy. The decision offers a new option for a disease the FDA described as aggressive and life-threatening, with a high need for effective treatments.

The decision was based on the multicenter, open-label, multi-cohort OrigAMI-4 trial, whose primary efficacy population included 102 patients with recurrent or metastatic head and neck cancer. That population did not include patients with HPV-associated oropharyngeal squamous cell carcinoma, according to p16 test results, and they are also excluded from the stated indication. Blinded independent central review assessed overall response rate and duration of response using RECIST v1.1 criteria. The overall response rate was 42%, while responses lasted six months or longer in 56% of patients who responded to treatment. The FDA said currently approved treatments are associated with an overall response rate of about 20% or less and poor outcomes, placing the trial result in the context of historically limited treatment options.

The FDA said treatment options had historically been limited and outcomes remained poor, according to Angelo De Claro, director of the agency’s Oncology Center of Excellence. The combination is administered as a single agent by subcutaneous injection, at a dose based on body weight, every 3 weeks. In the OrigAMI-4 trial, treatment continued until disease progression or unacceptable toxicity. This regimen specifies how the treatment is administered and the interval between doses for the patients included in the study. On December 17, 2025, the FDA had approved the same subcutaneous formulation for the indications then approved for the intravenous form of amivantamab. That earlier approval covered those indications, while the current decision adds recurrent or metastatic head and neck cancer to the stated scope of use.

The prescribing information includes warnings for hypersensitivity and administration-related reactions, interstitial lung disease or pneumonitis, skin effects, ocular toxicity and embryo-fetal toxicity. The FDA listed these risks among the precautions for using the combination as a single agent. The indication remains limited to adults whose disease progressed after platinum-based chemotherapy and an anti-PD-(L)1 drug. It also excludes HPV-associated oropharyngeal squamous cell carcinoma. The application received priority review, and the treatment was granted Breakthrough Therapy designation for this indication, according to the agency. These regulatory measures place the decision on an expedited review track, while the approval itself remains accelerated and contingent on verification of clinical benefit.

The FDA explained that accelerated approval may be granted early based on surrogate or intermediate endpoints, and that it required confirmatory studies to verify and describe the clinical benefit. The agency said the effect of the results on long-term outcomes has not yet been confirmed, making the required studies the next step in establishing clinical benefit. The application was reviewed under Project Orbis, in collaboration with regulatory authorities in Brazil, Canada, Israel and Singapore. The project provides a framework for simultaneous submission and review, but the FDA said applications in other countries may be under submission or review by their respective regulators. Accordingly, the November 5 decision covers approval by the U.S. agency, while applications in participating countries remain subject to their own regulatory processes. The FDA did not specify in its statement when the confirmatory studies would be completed or when other regulatory decisions would be made.