On November 5, 2026, the U.S. Food and Drug Administration (FDA) granted accelerated approval to amivantamab and hyaluronidase-lpuj (Rybrevant Faspro) for adults with recurrent or metastatic head and neck squamous cell carcinoma (HNSCC) whose disease has progressed on or after platinum-based chemotherapy and an anti–PD-(L)1 antibody. Amivantamab and hyaluronidase-lpuj is not indicated for patients with oropharyngeal squamous cell carcinoma (OPSCC) that is associated with human papillomavirus (HPV).
Efficacy and Safety
Efficacy was evaluated in the multicenter, open-label, multi-cohort OrigAMI‑4 trial (ClinicalTrials.gov Identifier NCT06385080). The primary efficacy population included 102 patients with recurrent or metastatic HNSCC. The primary efficacy population did not include patients with HPV-associated OPSCC based on p16 testing results. Eligible patients were required to have received previous treatment with platinum-based chemotherapy and an anti–PD-(L)1 antibody. Patients received single-agent weight-based amivantamab and hyaluronidase-lpuj subcutaneously every 3 weeks at the recommended dose until disease progression or unacceptable toxicity.
The major efficacy outcome measures were overall response rate and duration of response, determined by blinded independent central review (BICR) according to RECIST v1.1. Overall response rate was 42% (95% confidence interval [CI] = 32%–52%), with 56% of responders having a duration of response of at least 6 months.
The prescribing information for amivantamab and hyaluronidase-lpuj as a single agent includes warnings and precautions for hypersensitivity and administration-related reactions, interstitial lung disease/pneumonitis, dermatologic adverse reactions, ocular toxicity, and embryo-fetal toxicity.
Recommended Dosage
The recommended dose is based on body weight.
This review was conducted under Project Orbis. For this review, the FDA collaborated with Brazilian Health Regulatory Agency (ANVISA), Health Canada (HC), Israel Ministry of Health (IMoH), and Health Sciences Agency (HSA). The applications may be undergoing the submission process or still be under review at the other regulatory agencies.
This review also used the Assessment Aid, a voluntary submission from the applicant to facilitate the FDA’s assessment.
This application was also granted Priority Review. Amivantamab and hyaluronidase-lpuj previously received Breakthrough Therapy designation.
