FDA Grants Accelerated Approval to Amivantamab and Hyaluronidase-lpuj for Recurrent or Metastatic HNSCC

Overview

The FDA granted accelerated approval to subcutaneous amivantamab and hyaluronidase-lpuj for adults with recurrent or metastatic HNSCC that has progressed on or after platinum-based chemotherapy and anti-PD-(L)1 therapy. In the single-arm OrigAMI-4 trial, the overall response rate was 42%; accelerated approval was based on tumor response, with continued approval potentially dependent on verification of clinical benefit.

Background

The indication applies to previously treated recurrent or metastatic HNSCC and excludes HPV-associated oropharyngeal squamous cell carcinoma identified by p16 testing. Amivantamab is a bispecific antibody targeting EGFR and MET, and hyaluronidase facilitates subcutaneous delivery. The FDA described this as the first drug approval in 10 years for patients with recurrent or metastatic HNSCC previously treated with platinum-based chemotherapy. Recent SEOM–TTCC guidance describes first-line treatment options including pembrolizumab alone or with platinum and 5-FU, while post-progression options include cetuximab-containing regimens and taxanes.

Data Highlights

Key Findings

• The approved regimen is single-agent subcutaneous amivantamab and hyaluronidase-lpuj for adults whose recurrent or metastatic HNSCC progressed on or after platinum-based chemotherapy and an anti-PD-1 or anti-PD-L1 antibody.
• The indication excludes HPV-associated oropharyngeal squamous cell carcinoma, identified by p16 testing.
• OrigAMI-4 was an open-label, multicenter phase 1b/2 trial of 102 previously treated patients; overall response rate was the primary efficacy measure, with duration of response assessed by blinded independent central review.
• The overall response rate was 42%, comprising 15% complete responses and 28% partial responses; 56% of responders maintained response for at least 6 months.
• The FDA cited response rates of approximately 20% or less for previously approved therapies, but OrigAMI-4 did not directly compare amivantamab with those treatments.
• Warnings include 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.

Clinical Implications

The prescribing information specifies single-agent subcutaneous amivantamab and hyaluronidase-lpuj after platinum-based chemotherapy and an anti-PD-1 or anti-PD-L1 antibody, and excludes HPV-associated oropharyngeal squamous cell carcinoma identified by p16 testing. The label includes warnings for 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. Accelerated approval was based on tumor response, and continued approval may depend on verification of clinical benefit.

Conclusion

The FDA granted accelerated approval to amivantamab and hyaluronidase-lpuj for adults with recurrent or metastatic HNSCC whose disease progressed on or after platinum-based chemotherapy and anti-PD-1 or anti-PD-L1 therapy, excluding HPV-associated oropharyngeal disease. Approval was based on response data from OrigAMI-4. J&J identified the ongoing phase 3 OrigAMI-5 trial as the confirmatory study.

Related Resources & Content

1. U.S. Food and Drug Administration, FDA, 2026 — FDA grants accelerated approval to amivantamab and hyaluronidase-lpuj for recurrent or metastatic head and neck squamous cell carcinoma
2. SEOM–TTCC, PMC, 2025 — SEOM–TTCC clinical guidelines for the treatment of head and neck cancer
3. OrigAMI-4 investigators, PubMed, 2026 — Amivantamab in Recurrent/Metastatic Head and Neck Squamous Cell Cancer After Checkpoint Inhibitor and Chemotherapy: Pivotal Results From the Phase Ib/II OrigAMI-4 Study
4. Johnson & Johnson, study summary and prescribing information, year not specified — OrigAMI-4 study summary and Rybrevant Faspro prescribing information
5. the asco post — FDA Approves Amivantamab-vmjw for EGFR Exon 20 Insertion–Mutated NSCLC
6. the asco post — FDA Grants Accelerated Approval to Amivantamab-vmjw for Metastatic EGFR Exon 20 Insertion–Mutated NSCLC
7. The ASCO Post — FDA Grants Accelerated Approval to Amivantamab-vmjw for Metastatic EGFR Exon 20 Insertion–Mutated NSCLC
8. the asco post — Amivantamab-vmjw for Previously Treated Advanced NSCLC With EGFR Mutation
9. FDA grants accelerated approval to amivantamab and hyaluronidase-lpuj for recurrent or metastatic head and neck squamous cell carcinoma
10. SEOM–TTCC clinical guidelines for the treatment of head and neck cancer (2025)
11. Amivantamab in Recurrent/Metastatic Head and Neck Squamous Cell Cancer After Checkpoint Inhibitor and Chemotherapy: Pivotal Results From the Phase Ib/II OrigAMI-4 Study
12. SEOM–TTCC clinical guidelines for the treatment of head and neck cancer (2025) - PMC
13. Amivantamab in Recurrent/Metastatic Head and Neck Squamous Cell Cancer After Checkpoint Inhibitor and Chemotherapy: Pivotal Results From the Phase Ib/II OrigAMI-4 Study.