FDA Grants Priority Review to J&J’s Subcutaneous Amivantamab for HNSCC

Johnson & Johnson has received U.S. Food and Drug Administration (FDA) Priority Review for its supplemental Biologics License Application (sBLA) seeking approval of subcutaneous amivantamab and hyaluronidase-lpuj (RYBREVANT FASPRO™) for adults with recurrent or metastatic head and neck squamous cell carcinoma (HNSCC). The application covers patients whose disease has progressed after platinum-based chemotherapy and PD-1 or PD-L1 inhibitor therapy, a setting with limited treatment options and poor long-term outcomes.

Priority Review shortens the FDA review period to approximately six months and is reserved for therapies that could provide meaningful improvements in the treatment of serious diseases. If approved, subcutaneous amivantamab would expand beyond its established role in non-small cell lung cancer (NSCLC) into head and neck cancer.

Dual EGFR and MET Targeting Addresses Key Resistance Pathways

Amivantamab is a fully human bispecific antibody that simultaneously targets epidermal growth factor receptor (EGFR) and mesenchymal-epithelial transition (MET), two signaling pathways that contribute to tumor growth, disease progression, and treatment resistance. The antibody also engages immune effector mechanisms to promote tumor cell killing.

EGFR and MET overexpression occurs in approximately 80% to 90% of HNSCC tumors, making dual pathway inhibition a rational therapeutic strategy. RYBREVANT FASPRO™ combines amivantamab with recombinant human hyaluronidase PH20 (rHuPH20) using Halozyme’s ENHANZE® technology, enabling subcutaneous administration.

Head and neck squamous cell carcinoma remains a major global health challenge, accounting for approximately 4.5% of all cancers worldwide. Patients with recurrent or metastatic disease continue to face poor outcomes despite advances in surgery, radiation, chemotherapy, and immunotherapy. The five-year survival rate for advanced disease remains approximately 15%.

OrigAMI-4 Trial Demonstrated Strong Clinical Activity

The FDA’s Priority Review decision is supported by findings from the Phase 1b/2 OrigAMI-4 (NCT06385080) study evaluating subcutaneous amivantamab in recurrent or metastatic HNSCC.

The trial enrolled patients whose disease had progressed following platinum-based chemotherapy and PD-1/PD-L1 immunotherapy. Patients with HPV-positive oropharyngeal squamous cell carcinoma and those previously treated with anti-EGFR therapy were excluded.

The primary endpoint was investigator-assessed overall response rate (ORR) according to RECIST v1.1 criteria.

Key efficacy findings included:

• Overall response rate (ORR) of 42%
• More than one-third of responding patients achieved a complete response

Patients received weekly subcutaneous treatment during the initial treatment period followed by weight-based dosing every three weeks.

Safety Profile

The safety profile of subcutaneous amivantamab was consistent with its established safety profile, with no new safety signals reported. Overall tolerability was consistent with previous clinical experience with the therapy.

The pivotal findings were presented at the 2026 American Society of Clinical Oncology (ASCO) Annual Meeting and published simultaneously in the Journal of Clinical Oncology.

Expanding the Clinical Role of Subcutaneous Amivantamab

Yusri Elsayed, M.D., M.H.Sc., Ph.D., Global Therapeutic Area Head, Oncology at Johnson & Johnson, said advanced head and neck cancer can impair essential functions such as speaking, eating, and breathing, substantially affecting patients’ quality of life. He noted that treatment options remain limited after progression on standard therapies and said the FDA’s Priority Review highlights the broader potential of subcutaneous amivantamab across multiple EGFR- and MET-driven cancers.

RYBREVANT FASPRO™ is already approved in more than 40 countries, including the United States, Europe, and Japan, for selected EGFR-mutated non-small cell lung cancer indications. The subcutaneous formulation offers an alternative to intravenous administration while leveraging the established efficacy and safety profile of intravenous amivantamab demonstrated across multiple Phase 3 clinical trials.

Regulatory Development

The FDA is expected to complete its review under the Priority Review timeline in approximately six months. If approved, RYBREVANT FASPRO™ would become the first subcutaneous bispecific antibody targeting EGFR and MET for patients with recurrent or metastatic HNSCC whose disease has progressed after platinum-based chemotherapy and PD-1/PD-L1 inhibitor therapy.

Johnson & Johnson continues to evaluate RYBREVANT-based therapies across multiple solid tumors, including colorectal and head and neck cancers, reflecting ongoing efforts to expand the clinical utility of dual EGFR and MET inhibition.

Reference

Johnson & Johnson’s RYBREVANT FASPRO™ (amivantamab and hyaluronidase-lpuj) receives U.S. FDA Priority Review as potential first-in-class EGFR- and MET-targeted subcutaneous treatment for advanced head and neck cancer