FDA Clears J&J's Rybrevant Faspro, First Dual-Targeted Shot at Advanced HNSCC

The FDA handed an accelerated approval on Nov. 5 to amivantamab and hyaluronidase-lpuj (Rybrevant Faspro, Johnson & Johnson) for adults with recurrent or metastatic head and neck squamous cell carcinoma whose disease progressed on or after platinum-based chemotherapy and immunotherapy. It is the first and only dual-targeted therapy cleared for this population, and the first approval for the drug outside non-small cell lung cancer. It also marks the first new approval in 10 years for these previously treated HNSCC patients.

The drug goes after EGFR and MET at once — two drivers overexpressed in 80% to 90% of recurrent and metastatic HNSCC tumors, where they often signal poor prognosis. It is given as a 5-minute subcutaneous injection and also activates immune cell-directing activity. In EGFR-mutated NSCLC, the same combination is the only approved subcutaneous option, used as monotherapy or with lazertinib (Lazcluze) or chemotherapy depending on mutation and setting.

The green light rests on the ongoing phase 1b/2 OrigAMI-4 trial, which has six cohorts. In cohort 1, 102 participants who had progressed after a PD-L1 inhibitor and platinum chemotherapy received subcutaneous amivantamab every three weeks. Blinded independent central review found a confirmed overall response rate of 42%, with complete responses in 15% and partial responses in 27%, per data presented at the 2026 American Society of Clinical Oncology Annual Meeting. Fifty-six percent of responders held their response beyond six months.

At a median follow-up of 11.8 months, median progression-free survival hit 6.8 months and overall survival 12.5 months. Treatment-related discontinuations stayed low at 8%, and adverse events matched prior experience with no new safety signals; rash, fatigue, nail toxicity and edema were most common. Amanda Hollinger, executive director of the Head and Neck Cancer Alliance, called it "renewed hope for patients and their families" in a news release.

Barbara Burtness, MD, a medical oncologist and professor of medicine at Yale Cancer Center, said the OrigAMI-4 findings highlight dual EGFR- and MET-targeting as a distinct approach in recurrent or metastatic head and neck cancer, excluding HPV-associated oropharyngeal squamous cell carcinoma. The FDA's decision followed a Breakthrough Therapy Designation in February 2026 and Priority Review in July 2026. Continued approval may hinge on the phase 3 OrigAMI-5 confirmatory trial in first-line HNSCC.