Adults with recurrent or metastatic head and neck squamous cell carcinoma (HNSCC) whose disease has progressed on or after platinum-based chemotherapy and immunotherapy have a new treatment option following the US Food and Drug Administration's (FDA) accelerated approval of amivantamab and hyaluronidase-lpuj (Rybrevant Faspro).
The FDA announced the approval, granting it to Janssen Biotech, a Johnson & Johnson (J&J) company. The prescribing information specifies subcutaneous treatment as a single agent after platinum-based chemotherapy and an anti-PD-1 or anti-PD-L1 antibody. It excludes patients with human papillomavirus (HPV)-associated oropharyngeal squamous cell carcinoma, identified by p16 testing.
The therapy combines amivantamab, a bispecific antibody targeting epidermal growth factor receptor and mesenchymal-epithelial transition, with hyaluronidase to facilitate subcutaneous delivery. The agency described this as the first drug approval in 10 years for patients with recurrent or metastatic HNSCC previously treated with platinum-based chemotherapy.
Approval was supported by OrigAMI-4, an open-label, multicenter phase 1b/2 trial involving 102 previously treated patients. Participants received weight-based subcutaneous amivantamab and hyaluronidase-lpuj every 3 weeks until disease progression or unacceptable toxicity. The primary efficacy measure was overall response rate, with duration of response also assessed by blinded independent central review.
The overall response rate was 42%, including 15% complete responses and 28% partial responses. Among responders, 56% maintained their response for at least 6 months, according to J&J's study summary.
The FDA noted that previously approved therapies have response rates of approximately 20% or less, although OrigAMI-4 did not directly compare amivantamab with these treatments.
J&J's study summary reported serious treatment-emergent adverse events in 39% of patients. The prescribing information reported fatal adverse reactions in 6%. The most common adverse reactions were rash (79%), fatigue (39%), nail toxicity (35%), stomatitis (32%), and edema (28%).
The label also warns of hypersensitivity and administration-related reactions, interstitial lung disease/pneumonitis, dermatologic reactions, ocular toxicity, and embryo-fetal toxicity. Known hypersensitivity to hyaluronidase or its excipients is a contraindication.
"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 the agency's announcement.
Accelerated approval was based on tumor response measures rather than confirmed long-term clinical benefit. J&J identified the ongoing phase 3 OrigAMI-5 trial, evaluating a first-line combination regimen, as the confirmatory study. Continued approval may depend on verification of clinical benefit.
Sources: FDA press release, J&J press release, J&J study summary, and prescribing information
