Rybrevant Faspro becomes first dual-targeted therapy approved for advanced head and neck cancer – Johnson & Johnson

Johnson & Johnson announced that the FDA granted accelerated approval for RYBREVANT FASPRO (amivantamab and hyaluronidase-lpuj) (subcutaneous injection, 160 mg/2,000 units per mL) as a single agent for the treatment of adults with recurrent or metastatic head and neck squamous cell carcinoma (HNSCC) whose disease has progressed on or after platinum‑based chemotherapy and an anti‑PD‑(L)1 antibody.

The indication does not include patients with oropharyngeal squamous cell carcinoma (OPSCC) that is HPV-associated (i.e., by p16 immunohistochemistry). It is the first approval of a dual-targeted therapy in this setting, simultaneously targeting epidermal growth factor receptor (EGFR)- and mesenchymal-epithelial transition (MET).

The approval follows the FDA Breakthrough Therapy Designation (BTD) granted in February 2026 and Priority Review designation in July 2026. This indication was granted accelerated approval based on clinically meaningful and durable tumor response demonstrated in the Phase 1b/2 OrigAMI-4 trial.

i) Overall Response Rate (ORR): Confirmed ORR was 42 percent (95 percent confidence interval [CI], 32–52 percent), including complete responses in 15 percent of patients, representing one-third of all responders, and partial responses in 28 percent of patients, per blinded independent central review (BICR).

ii) Duration of Response (DOR): 56 percent of responders maintained a response for more than six months (1.4+, 19.7+), per BICR.

Continued approval may be contingent upon verification and description of clinical benefit in the ongoing confirmatory trial in first-line HNSCC, the Phase 3 OrigAMI-5 study.

Expert perspectives on improving outcomes for patients with head and neck cancer

“For people living with recurrent or metastatic head and neck cancer, the stakes are incredibly high. I’ve seen firsthand that when the disease progresses, patients often face limited treatment options, while managing symptoms that can affect their ability to eat, speak, swallow and breathe,” said Amanda Hollinger, Executive Director, Head and Neck Cancer Alliance. “At a time when treatment advances are urgently needed to improve outcomes for patients, this new option offers renewed hope for patients and their families.”

“Outcomes remain poor for patients whose head and neck cancer progresses, and treatment options are limited,” said Barbara Burtness, M.D., medical oncologist and professor of medicine at Yale Cancer Center in New Haven, Connecticut. “The OrigAMI-4 findings represent important progress and highlight the potential of dual EGFR- and MET-targeting with amivantamab as a distinct treatment approach in recurrent or metastatic head and neck cancer, excluding HPV-associated oropharyngeal squamous cell carcinoma. The meaningful responses observed in this study are encouraging for patients who have long faced limited treatment options.”

First Approval for RYBREVANT FASPRO Beyond Lung Cancer

EGFR and MET are key drivers of tumor progression, overexpressed in 80 to 90 percent of recurrent and metastatic HNSCC tumors and often associated with poor prognosis. RYBREVANT FASPRO addresses this by targeting both the EGFR and MET pathways simultaneously, while activating immune-cell directing activity – delivered via a five-minute subcutaneous injection.

This approval marks the first indication beyond non-small cell lung cancer (NSCLC) for RYBREVANT FASPRO. It reinforces the potential of the EGFR– and MET-targeted mechanism of amivantamab across multiple difficult-to-treat tumors.

“For years, treatment advances in recurrent or metastatic head and neck cancer have been limited by approaches that do not fully address the underlying biology of the disease,” said Yusri Elsayed, M.D., M.H.Sc., Ph.D., Global Therapeutic Head, Oncology, Johnson & Johnson Innovative Medicine. “RYBREVANT FASPRO delivers a differentiated approach, targeting both EGFR and MET to address the biology that drives this disease. Having redefined outcomes in EGFR+ non-small cell lung cancer, we are unlocking the next chapter of this treatment and bringing meaningful innovation to patients with certain head and neck cancers.”

Pivotal Study Results

The FDA accelerated approval is supported by data from the multi-cohort Phase 1b/2 OrigAMI-4 trial. Cohort 1 evaluated RYBREVANT FASPRO as a single agent in 102 adults with previously treated recurrent or metastatic HNSCC who have received platinum-based chemotherapy and an anti‑PD‑(L)1 antibody (excluding patients with HPV-positive OPSCC). The pivotal results were presented at the 2026 American Society of Clinical Oncology (ASCO) Annual Meeting and published in the Journal of Clinical Oncology.

Safety

In the OrigAMI-4 trial, the safety profile of RYBREVANT FASPRO was consistent with the well-established safety profile of prior amivantamab experience. No new safety signals were identified, supporting a favorable benefit-risk profile for this advanced patient population. The most common adverse reactions occurring 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. Serious adverse reactions in at least 2 percent of patients included pneumonia (8 percent), hemorrhage (4.9 percent), dysphagia (2.9 percent), pneumothorax (2.9 percent), anemia (2 percent), dyspnea (2 percent), fatigue (2 percent), hepatic enzyme increased (2 percent), and ILD/pneumonitis (2 percent). Fatal adverse reactions occurred in 6 percent of patients who received RYBREVANT FASPRO, including sudden death (2 percent), myocardial ischemia, tumor hemorrhage, aspiration pneumonia, and ILD/pneumonitis (1 percent, one patient each).

About the OrigAMI-4 Study

OrigAMI-4 is a multi-cohort, multicenter, open-label, ongoing Phase 1b/2 study evaluating RYBREVANT FASPRO (amivantamab and hyaluronidase-lpuj) in recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC). The study includes six cohorts exploring RYBREVANT FASPRO across different treatment settings and regimens. Cohort 1 (n=102) evaluated the efficacy and safety of RYBREVANT FASPRO as a single agent in patients with previously treated R/M HNSCC whose disease has progressed on or after platinum-based chemotherapy and an anti-PD-(L)1 antibody. Patients with HPV-associated OPSCC were excluded from Cohort 1. Patients received weight-based RYBREVANT FASPRO every three weeks at the recommended dose and schedule until disease progression or unacceptable toxicity. The primary endpoint is overall response rate (ORR), and the secondary endpoint is duration of response (DOR), both assessed by blinded independent central review (BICR) using RECIST v1.1.

Citation: Burtness B, et al. Amivantamab in recurrent/metastatic HNSCC after checkpoint inhibitor and chemotherapy: pivotal results from the phase 1b/2 OrigAMI-4 study. Epub May 31, 2026. doi:10.1200/JCO-26-01042.