Johnson & Johnson: FDA Priority Review for potential first-in-class subcutaneous RYBREVANT FASPRO in recurrent/metastatic HNSCC
- FDA granted Priority Review to the sBLA for subcutaneous amivantamab and hyaluronidase-lpuj for adults with recurrent or metastatic HNSCC, shortening review to about six months.
- Pivotal Phase 1b/2 OrigAMI-4 reported a 42% overall response rate with more than one-third of responders achieving complete responses; HPV-positive oropharyngeal cases and prior anti-EGFR therapy were excluded.
- Amivantamab FASPRO is designed to target both EGFR and MET, receptors overexpressed in 80–90% of HNSCC tumors.
- RYBREVANT FASPRO is co-formulated with recombinant human hyaluronidase PH20 (ENHANZE) and is approved in over 40 countries, including U.S. approval in December 2025 for EGFR‑mutated NSCLC.
Regulatory update
The U.S. FDA has granted Priority Review to the supplemental Biologics License Application for subcutaneous amivantamab and hyaluronidase-lpuj (RYBREVANT FASPRO) in adults with recurrent or metastatic head and neck squamous cell carcinoma (HNSCC) whose disease progressed after platinum chemotherapy and a PD-1/PD-L1 inhibitor. Priority Review shortens the agency review timeline to approximately six months.
Supporting clinical data
The Priority Review was supported by pivotal results from the Phase 1b/2 OrigAMI-4 study, which reported a 42% overall response rate for monotherapy subcutaneous amivantamab, with more than one-third of responders achieving a complete response. The cohort excluded patients with HPV-positive oropharyngeal squamous cell carcinoma and those with prior anti-EGFR therapy. Findings were presented at ASCO 2026 and published in the Journal of Clinical Oncology.
Product profile and positioning
RYBREVANT FASPRO is a subcutaneous co-formulation of amivantamab and hyaluronidase-lpuj using recombinant human hyaluronidase PH20 (ENHANZE) delivery technology. It is designed to target both EGFR and MET while engaging the immune system; EGFR and MET overexpression is reported in 80–90% of HNSCC tumors. The subcutaneous formulation is approved in more than 40 countries and received U.S. approval in December 2025 for EGFR‑mutated non‑small cell lung cancer.
Study design and dosing
OrigAMI-4 (NCT06385080) is an open-label Phase 1b/2 study with six cohorts exploring RYBREVANT FASPRO across settings. In cohort 1 the drug was given weekly during the initial period then every three weeks with weight-based dosing; the primary endpoint across cohorts is investigator-assessed overall response rate per RECIST v1.1.
Source: J&J