FDA Grants Priority Review to Subcutaneous Amivantamab for Advanced HNSCC

The FDA has granted a priority review designation to the supplemental biologics license application (sBLA) for subcutaneous amivantamab and hyaluronidase-lpuj (Rybrevant Faspro) for the treatment of adults with recurrent or metastatic head and neck squamous cell carcinoma (HNSCC) whose disease has progressed following platinum-based chemotherapy and a PD-1/PD-L1 inhibitor.¹

The application is supported by pivotal results from the phase 1b/2 OrigAMI-4 study (NCT06385080). Among 102 patients with human papillomavirus (HPV)-unrelated recurrent or metastatic HNSCC who received at least 1 dose of subcutaneous amivantamab, the blinded independent central review-assessed objective response rate (ORR) was 42% (95% CI, 32%-52%), including a complete response (CR) rate of 15% and a partial response rate of 27%.² Investigator-assessed ORR was 47% (95% CI, 37%-57%), and 84% of evaluable patients achieved target-lesion shrinkage.

Responses were rapid, with a median time to first response of 6.6 weeks (range, 5.6-43.4), and durable, with a median duration of response (DOR) not reached (95% CI, 6.9-not reached); 56% of responses lasted at least 6 months and 63% were ongoing at the time of the analysis. At a median follow-up of 11.8 months (range, 1.1-21.9), median progression-free survival (PFS) was 6.8 months (95% CI, 5.2-8.3) and median overall survival (OS) was 12.5 months (95% CI, 10.2-16.8).²

The OrigAMI-4 data were presented in an oral session at the 2026 American Society of Clinical Oncology Annual Meeting and simultaneously published in the Journal of Clinical Oncology.² The study enrolled patients with HPV-unrelated disease and excluded those who had received prior anti-EGFR therapy.¹

“Patients with recurrent or metastatic head and neck cancer who have already been treated with immunotherapy and chemotherapy face very poor outcomes," Barbara Burtness, MD, medical oncologist and professor of medicine at Yale Cancer Center in New Haven, Connecticut, stated at the time the data were presented at ASCO. “The high response seen with subcutaneous amivantamab on its own, including more than one-third of responders achieving complete responses, and the durability of those responses, suggests it has the potential to meaningfully improve expectations for these patients.”

Safety of Subcutaneous Amivantamab

Treatment-emergent adverse events (AEs) were consistent with the established safety profile of amivantamab and its dual EGFR and MET mechanism, with no new safety signals identified.² The most common AEs occurring in more than 25% of patients were hypoalbuminemia, rash, dermatitis acneiform, paronychia, stomatitis, and fatigue, reflecting the expected on-target toxicities of EGFR and MET inhibition. Administration-related reactions occurred in 13% of patients and were all grade 1 or 2. Treatment-related discontinuations were low at 8%.²

OrigAMI-4 Study Design and Patient Population

Subcutaneous amivantamab is a bispecific antibody designed to inhibit EGFR and MET simultaneously, which are overexpressed in a high proportion of HNSCC tumors. The open-label phase 1b/2 OrigAMI-4 study evaluated subcutaneous amivantamab in patients with HNSCC and other solid tumors. Cohort 1, which provided the data supporting the sBLA, enrolled adults with HPV-unrelated recurrent or metastatic HNSCC whose disease had progressed on or after a PD-1/PD-L1 inhibitor and platinum-based chemotherapy; patients with prior anti-EGFR therapy were excluded.^1,2

Subcutaneous amivantamab was administered at 1600 mg (2240 mg for patients weighing at least 80 kg) on cycle 1 day 1, and 2400 mg (3360 mg for patients weighing at least 80 kg) thereafter, every 3 weeks. The primary endpoint was ORR per RECIST v1.1; secondary endpoints included DOR, PFS, OS, and safety. The median patient age was 63.5 years; 45% of patients were Asian and 43% were White.²

The FDA had previously granted breakthrough therapy designation to subcutaneous amivantamab for this indication in February 2026, based on preliminary data presented at the 2025 European Society for Medical Oncology Congress.³

"One of the hardest things about advanced head and neck cancer is that it can impact our most basic functions, like the ability to speak, eat, and even breathe easily, profoundly affecting patients' daily lives. For those whose disease progresses despite prior treatment, that burden is compounded by limited treatment options and poor outcomes," Yusri Elsayed, MD, MHSc, PhD, global therapeutic area head, Oncology, Johnson & Johnson stated in a news release.¹ "Building on the established role of subcutaneous amivantamab in lung cancer, this milestone underscores its continued potential across multiple tumor types and reflects our commitment to bringing innovative treatment options to patients with cancers driven by EGFR and MET pathways."

REFERENCES

1. Johnson and 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 and Johnson. July 30, 2026. Accessed July 30, 2026. https://tinyurl.com/4djefm52

2. Burtness B, Harrington KJ, Ji D, et al. Amivantamab in recurrent/metastatic HNSCC after checkpoint inhibitor and chemotherapy: pivotal results from the phase 1b/2 OrigAMI-4 study. J Clin Oncol. Published online May 31, 2026. doi:10.1200/JCO-26-01042

3. Rybrevant Faspro (amivantamab and hyaluronidase-lpuj) receives U.S. FDA Breakthrough Therapy Designation for patients with advanced head and neck cancer. News release. Johnson and Johnson. February 18, 2026. Accessed July 30, 2026. https://tinyurl.com/mtnfm2t3