NEW BRUNSWICK, N.J. – November 06, 2026 -- The U.S. Food and Drug Administration has granted accelerated approval to Johnson & Johnson's RYBREVANT FASPRO (amivantamab and hyaluronidase-lpuj) for recurrent or metastatic head and neck squamous cell carcinoma (HNSCC), backed by a confirmed 42 percent overall response rate in a 102-patient cohort.
Approval covers post-platinum, post-immunotherapy patients and excludes HPV-associated oropharyngeal disease
The subcutaneous single-agent therapy is cleared for adults whose disease progressed on or after platinum-based chemotherapy and an anti-PD-(L)1 antibody. The indication excludes patients with HPV-associated oropharyngeal squamous cell carcinoma (OPSCC). J&J says it is the first dual-targeted therapy approved in this setting, hitting both EGFR and MET, and describes it as the first advance in second-line treatment of the disease in a decade.
The decision follows FDA Breakthrough Therapy Designation in February 2026 and Priority Review in July 2026. It is the first approval for the product beyond non-small cell lung cancer.
OrigAMI-4 Cohort 1 shows 42 percent response rate, with 15 percent complete responses
The approval rests on Cohort 1 of the Phase 1b/2 OrigAMI-4 trial. Confirmed ORR was 42 percent (95 percent CI, 32-52 percent) by blinded independent central review. Complete responses occurred in 15 percent of patients, equal to one-third of all responders, and partial responses in 28 percent.
Of responders, 56 percent maintained their response for more than six months. Observed durations ranged from 1.4+ to 19.7+ months. Patients received weight-based dosing every three weeks until progression or unacceptable toxicity. Results were presented at the 2026 ASCO Annual Meeting and published in the Journal of Clinical Oncology.
Serious adverse reactions hit 39 percent of patients; fatal events reached 6 percent
J&J reports no new safety signals versus prior amivantamab experience. The most common adverse reactions, each 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 reactions included pneumonia (8 percent) and hemorrhage (4.9 percent). Fatal reactions included sudden death (2 percent), with myocardial ischemia, tumor hemorrhage, aspiration pneumonia and ILD/pneumonitis each in one patient.
The label carries a contraindication for known hypersensitivity to hyaluronidase or its excipients. Warnings cover administration-related reactions, interstitial lung disease, dermatologic and ocular toxicity, and embryo-fetal toxicity.
EGFR and MET overexpression in 80 to 90 percent of tumors underpins the dual-targeting rationale
Per the source, EGFR and MET are overexpressed in 80 to 90 percent of recurrent and metastatic HNSCC tumors. The drug is delivered as a five-minute subcutaneous injection and is co-formulated with Halozyme's ENHANZE technology. Roughly 80 percent of recurrent or metastatic HNSCC cases are not HPV-driven and typically carry a poorer prognosis. HNSCC accounts for approximately 4.5 percent of cancers worldwide and is the seventh most common cancer globally.
Yusri Elsayed, Global Therapeutic Head, Oncology at J&J, said the product takes a differentiated approach by addressing the biology driving the disease.
Continued approval hinges on Phase 3 OrigAMI-5 first-line confirmatory study
Continued approval may depend on verification of clinical benefit in the ongoing Phase 3 OrigAMI-5 trial in first-line HNSCC. OrigAMI-4 itself includes six cohorts testing the therapy across different treatment settings and regimens.