J&J's Rybrevant Wins the First New Second-Line Head and Neck Cancer Drug in a Decade
The FDA cleared J&J's Rybrevant Faspro for recurrent head and neck cancer, the first new drug in that second-line setting in a decade, on a 42% response rate and a 15% complete-response share.
Johnson & Johnson on November 5, 2026, won U.S. Food and Drug Administration accelerated approval for Rybrevant Faspro, a subcutaneous injection of amivantamab and hyaluronidase-lpuj, in adults with recurrent or metastatic head and neck squamous cell carcinoma whose disease has progressed on or after platinum-based chemotherapy and an anti-PD-(L)1 immunotherapy. The indication excludes HPV-associated oropharyngeal squamous cell carcinoma.
The decision is the first approval in 10 years of a drug for patients with recurrent or metastatic HNSCC who had already received platinum-based chemotherapy. For J&J, it is also the first indication for Rybrevant Faspro beyond non-small cell lung cancer, where the drug is already approved across multiple EGFR-mutated populations.
That is the franchise story: a lung-cancer bispecific stepping into a second-line setting that had gone a decade without a new drug. The clinical story is harder. In the supporting trial, 42 percent of patients responded, roughly double the around 20 percent ceiling of existing approved therapies, and 15 percent had complete responses. The label is still an accelerated approval, and 6 percent of trial patients had fatal adverse reactions.
A 42 percent response rate against a 20 percent bar
Approval rests on OrigAMI-4, a Phase 1b/2 trial. Cohort 1 enrolled 102 patients. Per blinded independent central review, the overall response rate was 42 percent, with a 95 percent confidence interval of 32 to 52 percent. Complete responses occurred in 15 percent of patients, or one-third of all responders. Partial responses occurred in 28 percent. Among responders, 56 percent maintained a response for six months or longer.
Existing approved therapies are associated with an overall response rate of around 20 percent or less. The FDA said more than double the percentage of patients responded compared with currently approved therapies. J&J's release also set out the safety profile that will travel with the drug: the most common adverse reactions in at least 20 percent of patients were rash (79 percent), fatigue (39 percent), nail toxicity (35 percent), stomatitis (32 percent), and edema (28 percent). Serious adverse reactions occurred in 39 percent of patients. Fatal adverse reactions occurred in 6 percent.
EGFR, MET, and a non-HPV majority
Rybrevant is a first-in-class, fully-human bispecific antibody that simultaneously targets EGFR and MET, two drivers of tumor progression that are overexpressed in 80 to 90 percent of recurrent or metastatic HNSCC tumors. That biology is why J&J could take the same molecule out of EGFR-mutated lung cancer and into head and neck disease, and it also fits the HPV carve-out on the label.
HNSCC accounts for roughly 4.5 percent of all cancers worldwide and is the seventh most common cancer globally. About 80 percent of recurrent or metastatic HNSCC is not HPV-driven. The approved population is that non-HPV majority after platinum chemotherapy and checkpoint blockade have already failed. The FDA granted Breakthrough Therapy designation in February 2026 and Priority Review in July 2026.
The confirmatory trial is the real product test
Continued approval is contingent on verification of clinical benefit in an ongoing confirmatory trial, the Phase 3 OrigAMI-5 study in first-line HNSCC. OrigAMI-4 got the drug onto the second-line label. OrigAMI-5 will determine whether that label holds, and whether amivantamab can move earlier in the same disease.
J&J has now extended its flagship EGFR-MET bispecific beyond lung cancer, into a HNSCC population that had waited 10 years for a new second-line option, with a response rate that roughly doubles the existing bar and complete responses in 15 percent of patients. The same dataset shows serious adverse reactions in 39 percent of patients and fatal adverse reactions in 6 percent. Until OrigAMI-5 reads out, the head and neck expansion rests on an accelerated approval that the FDA can withdraw if the confirmatory trial disappoints.
