Subcutaneous Amivantamab Earns Breakthrough Therapy Designation in HNSCC

The FDA has granted breakthrough therapy designation to subcutaneous amivantamab and hyaluronidase-lpuj (Rybrevant Faspro) for the treatment of patients with human papillomavirus (HPV)–unrelated advanced head and neck squamous cell carcinoma (HNSCC) following disease progression on or after platinum-based chemotherapy and a PD-(L)1 inhibitor, according to a news release from the developer, Johnson & Johnson.¹

Supporting the regulatory decision were findings from the phase 1b/2 OrigAMI-4 trial (NCT06385080) presented at the 2025 European Society of Medical Oncology (ESMO) Congress, which exhibited clinical activity, including rapid and durable responses, in this pretreated population.^2,3 Among 38 efficacy-evaluable patients treated with subcutaneous amivantamab, an overall response rate (ORR) of 45% (95% CI, 29%-62%) was observed in those with relapsed/metastatic HNSCC.

Additional data revealed that the median time to response was 6.4 weeks (range, 5.7-18.3) with a median duration of response (DOR) of 7.2 months (95% CI, 5.3-not evaluable [NE]). Moreover, 82% of patients experienced shrinkage of their tumors after 8.3 months of follow-up. The median progression-free survival (PFS) was 6.8 months (95% CI, 4.2-9.0), and the median overall survival (OS) was not reached (95% CI, 7.7-NE).

“These data highlight the broader potential of [amivantamab]-based therapies across solid tumors where the EGFR and/or MET pathways are activated,” Kiran Patel, vice president and global head of Solid Tumor Clinical Development and Diagnostics at Johnson & Johnson Innovative Medicine, said in the news release on the study findings.³ “[Amivantamab] combinations have already demonstrated significant results for certain patients with non–small cell lung cancer, leading to extended survival and delayed treatment resistance. Now, we’re building on that progress in other hard-to-treat diseases like head and neck cancer. By targeting EGFR and MET while also engaging the immune system, subcutaneous amivantamab could provide new options for more patients who have few effective treatments.”

The phase 1b/2 study included 5 cohorts, the first of which evaluated the amivantamab-based combination in the HPV-unrelated advanced HNSCC population. Patients received amivantamab/hyaluronidase every 3 weeks at 2400 mg or 3360 mg for those weighing less than 80 kg or 80 kg or more, respectively.

The primary end point for cohort 1 of the study was ORR per RECIST v1.1 criteria. Secondary end points included DOR, clinical benefit rate, PFS, OS, and safety.⁴

Among 86 patients evaluable for safety who received at least 1 study dose, the profile was consistent with prior studies evaluating the amivantamab-based combination. No new signals emerged. The most common treatment-emergent adverse effects (TEAEs) included fatigue (31%), hypoalbuminemia (31%), and stomatitis (23%).

Infusion-related reactions occurred in 7% of patients, all grade 1 or 2, with no severe events. Additionally, 2% of patients discontinued treatment due to treatment-related AEs.

“Patients with HPV-unrelated recurrent or metastatic head and neck cancer often [have] rapid disease progression and have limited treatment options,” Patel stated in the news release on the regulatory decision.¹ “Receiving breakthrough therapy designation underscores the FDA's recognition of these early clinical data and the urgent need for new therapies. Dual targeting EGFR and MET has shown meaningful clinical benefit in lung cancer, helping patients live longer by changing disease biology and preventing treatment resistance. We are now applying this same multi-targeted approach in head and neck cancer with the goal of improving outcomes for patients.”

Subcutaneous amivantamab is undergoing further evaluation in the phase 3 OrigAMI-5 study (NCT07276399) in combination with pembrolizumab (Keytruda) and carboplatin as a first-line treatment among those with HPV-unrelated recurrent or metastatic HNSCC.

References

1. 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 February 19, 2026. https://tinyurl.com/49ynu5pk
2. Harrington KJ, Rosenberg A, Yang MH, et al. Amivantamab in recurrent/metastatic head & neck squamous cell cancer (HNSCC) after disease progression on checkpoint inhibition and chemotherapy: results from the phase Ib/II OrigAMI-4 study. Ann Oncol. 2025;36(suppl 2):S773. doi:10.1016/j.annonc.2025.08.1959
3. Subcutaneous amivantamab delivers promising 45 percent overall response rate with median duration of 7.2 months in recurrent or metastatic head and neck cancer. News release. Johnson & Johnson. October 19, 2025. Accessed February 19, 2026. https://tinyurl.com/uucf72mt
4. A study of amivantamab alone or in addition to other treatment agents in participants with head and neck cancer (OrigAMI-4). ClinicalTrials.gov. Updated February 13, 2026. Accessed February 19, 2026. https://tinyurl.com/4kptsjbr