Subcutaneous Amivantamab Receives FDA Priority Review in R/M HNSCC

The FDA has granted priority review to a supplemental biologics license application (sBLA) for amivantamab and hyaluronidase-lpuj (Rybrevant Faspro), administered subcutaneously, for adult patients with recurrent or metastatic head and neck squamous cell carcinoma (HNSCC), according to a news release from Johnson & Johnson.¹

If approved, subcutaneous amivantamab would be a first-in-class option targeting both epidermal growth factor receptor (EGFR) and mesenchymal-epithelial transition (MET) in this setting. The application is supported by data from Cohort 1 of the phase 1b/2 OrigAMI-4 trial (NCT06385080), in which subcutaneous amivantamab monotherapy was evaluated in patients with human papillomavirus (HPV)-unrelated recurrent/metastatic HNSCC following disease progression on checkpoint inhibitor immunotherapy and platinum-based chemotherapy.² Amivantamab/hyaluronidase is already approved in more than 40 countries as a subcutaneous treatment for EGFR-mutated non–small cell lung cancer (NSCLC).

What efficacy data support the sBLA?

In the efficacy population of Cohort 1 (n = 38), which required at least 2 disease assessments or treatment discontinuation for any reason, the confirmed investigator-assessed ORR was 45% (95% CI, 29%-62%), including 1 complete response and 16 partial responses. The clinical benefit rate (CBR), defined as confirmed response or durable stable disease, was 76% (95% CI, 60%-89%). The median time to first response was 6.4 weeks (range, 5.7-18.3), and the median duration of response (DOR) was 7.2 months (95% CI, 5.3-not estimable), with 47% of the 17 confirmed responders maintaining a response for at least 6 months.

The median progression-free survival (PFS) was 6.8 months (95% CI, 4.2-9.0), and 82% of patients experienced some degree of tumor shrinkage in target lesions. The overall survival (OS) data remained immature as of the July 1, 2025, data cutoff.

How was safety and tolerability characterized in OrigAMI-4?

Among the 86 patients in the safety population, 92% had at least 1 treatment-emergent adverse effect (TEAE), 47% had a grade 3 or higher TEAE, and 34% had a serious TEAE. The most frequent TEAEs related to EGFR inhibition included stomatitis (23%), dermatitis acneiform (20%), rash (19%), and paronychia (17%); TEAEs related to MET inhibition included hypoalbuminemia (31%) and peripheral edema (14%).

Administration-related reactions to the subcutaneous formulation occurred in 7% of participants, all grade 1 or 2, which the investigators noted was consistent with prior reports of subcutaneous amivantamab in NSCLC. TEAEs led to dose interruption, reduction, or discontinuation in 43%, 17%, and 7% of patients, respectively; discontinuation due to a treatment-related AE occurred in 2% of patients. The authors concluded that no new safety signals were identified relative to previous reports of amivantamab.

How was Cohort 1 of OrigAMI-4 designed?

OrigAMI-4 is a global, multicenter, open-label, multi-arm trial evaluating subcutaneous amivantamab as monotherapy and in combination with other standard-of-care agents across 5 cohorts in recurrent/metastatic HNSCC. Cohort 1 enrolled adults with histologically confirmed, HPV-unrelated recurrent/metastatic HNSCC arising in the oropharynx, oral cavity, hypopharynx, or larynx, considered incurable by local therapies. Patients had an ECOG performance status of 0 or 1 and disease progression on or after prior anti-PD-(L)1 checkpoint inhibitor and platinum-based chemotherapy. Those with prior anti-EGFR therapy or more than 2 prior lines of systemic therapy in the recurrent/metastatic setting were excluded.

Subcutaneous amivantamab, co-formulated with recombinant human hyaluronidase, was dosed at 1600 mg––2240 mg for patients weighing 80 kg or more––on cycle 1 day 1, followed by weekly doses of 2400 mg––3360 mg for those weighing 80 kg or more––for the remainder of cycle 1. In each subsequent cycle, patients received 2400 mg––3360 mg for those weighing 80 kg or more––every 3 weeks.

The primary end point was investigator-assessed ORR by RECIST v1.1; secondary end points included CBR, DOR, PFS, OS, and safety.

What is amivantamab’s regulatory history in HNSCC?

The FDA previously granted breakthrough therapy designation (BTD) to subcutaneous amivantamab monotherapy for HPV-unrelated recurrent/metastatic HNSCC in February 2026, based on the same OrigAMI-4 data, which had been presented in a mini-oral session at the European Society for Medical Oncology (ESMO) Congress 2025.³ Amivantamab is also being evaluated in the phase 3 OrigAMI-5 trial (NCT07276399), assessing subcutaneous amivantamab plus pembrolizumab (Keytruda) and carboplatin vs 5-fluorouracil plus pembrolizumab and platinum-based chemotherapy as first-line treatment for HPV-unrelated recurrent/metastatic HNSCC regardless of PD-L1 expression.⁴ Intravenous amivantamab-vmjw (Rybrevant) is approved in the US, EU, and other countries across multiple EGFR-mutated NSCLC settings, and amivantamab is separately being studied in phase 3 trials for colorectal cancer.

References

1. Johnson & Johnson. 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 July 30, 2026. https://tinyurl.com/4ercx9js
2. Harrington KJ, Rosenberg AJ, Yang MH, et al. Subcutaneous amivantamab in recurrent/metastatic head and neck squamous cell cancer after disease progression on checkpoint inhibitor and chemotherapy: preliminary results from the phase 1b/2 OrigAMI-4 study. Oral Oncol. 2025;171:107791. doi:10.1016/j.oraloncology.2025.107791
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 & Johnson. February 18, 2026. Accessed July 30, 2026. https://tinyurl.com/3nnea885
4. A study of amivantamab in addition to standard of care agents (SOC) compared with SOC alone in participants with recurrent/metastatic head and neck cancer (OrigAMI-5). ClinicalTrials.gov. Updated July, 6, 2026. Accessed July 30, 2026. https://tinyurl.com/34thc7s3