FDA Approves SC Amivantamab for Recurrent/Metastatic HNSCC

The FDA has approved subcutaneous amivantamab and hyaluronidase-lpuj (Rybrevant Faspro) for adult patients with recurrent or metastatic head and neck squamous cell carcinoma (HNSCC) following progression on or after platinum‑based chemotherapy and an anti‑PD‑(L)1 antibody, according to a news release from the developer, Johnson & Johnson.¹ This decision represents the the first approval of a dual-targeted therapy in this treatment setting.

The approval was based on data from the phase 1b/2 OrigAMI-4 trial (NCT06385080), in which investigators assessed subcutaneous amivantamab among patients with recurrent or metastatic HNSCC. Cohort 1 of the trial included 102 adults who received platinum-based chemotherapy and an anti–PD-(L)1 antibody.

Topline data showed an overall response rate (ORR) of 42% (95% CI, 32%-52%), which included complete responses (CRs) in 15% of patients. Additionally, 28% of patients had a partial response (PR). Among those with a response, 56% sustained their response for more than 6 months.

The safety profile of subcutaneous amivantamab in the OrigAMI-4 trial was comparable with previous reports of the agent, and no new safety signals were identified. The most common toxicities included rash (79%), faitgue (39%), nail toxicity (35%), and stomatitis (32%). Serious adverse effects included pneumonia (8%), hemorrhage (4.9%), and dysphagia (2.9%).

Subcutaneous amivantamab is contraindicated in patients with known hypersensitivity to hyaluronidase or any of its excipients. Other warnings and precautions include hypersensitivity and administration-related reactions, interstitial lung disease/pneumonitis, dermatologic adverse reactions, ocular toxicity and embryo-fetal toxicity.

Continued approval for subcutaneous amivantamab in this indication may be dependent on verification of clinical benefit in the ongoing confirmatory phase 3 OrigAMI-5 trial (NCT07276399), which is evaluating the agent in the first-line setting.

“Outcomes remain poor for patients whose head and neck cancer progresses, and treatment options are limited. 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,” Barbara Burtness, MD, a medical oncologist and professor of medicine at Yale Cancer Center in New Haven, Connecticut, stated in the press release.¹ “The meaningful responses observed in this study are encouraging for patients who have long faced limited treatment options.”

The primary end point of the OrigAMI-4 study was ORR. The secondary end point was DOR. Both end points were evaluated based on blinded independent central review using RECIST v1.1 guidelines. Amivantamab and hyaluronidase-lpuj is indicated at a subcutaneous dose of 160 mg/2000 units per mL.

The FDA previously granted priority review to subcutaneous amivantamab for this patient population in July 2026.²

“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. 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,” Amanda Hollinger, executive director of the Head and Neck Cancer Alliance, stated in the press release.¹

References

1. Johnson & Johnson announces U.S. FDA Approval of RYBREVANT FASPRO™ (amivantamab and hyaluronidase-lpuj) as first and only dual-targeted therapy for advanced head and neck cancer. News release. Johnson & Johnson. November 5, 2026. Accessed November 5, 2026. https://tinyurl.com/mr4999km
2. Johnson & Johnson's Rybrevant Faspro (amivantamab and hyaluronidase-lpuj) receives U.S. FDA priority review as potential first-in-class EGFR- and MET- targeted subcutaneous treatment for advanced head and neck cancer. News release. Johnson & Johnson. July 30, 2026. Accessed November 5, 2026. https://tinyurl.com/4ercx9js