FDA Grants Breakthrough Therapy Designation to Subcutaneous Amivantamab in HPV-Unrelated Head and Neck Squamous Cell Carcinoma
Key Clinical Summary:
- The FDA has granted breakthrough therapy designation to subcutaneous amivantamab plus hyaluronidase based on results from cohort 1 of the phase 1b/2 OrigAMI-4 study evaluating the agent in patients with HPV-unrelated recurrent or metastatic head and neck squamous cell carcinoma previously treated with platinum-based chemotherapy and a PD-1/PD-L1 inhibitor.
- Subcutaneous amivantamab demonstrated a confirmed objective response rate of 41% in the efficacy-evaluable population, with a median duration of response of 7.2 months and a median time to initial response of 6.4 weeks. The clinical benefit rate was 88%, and 85% of responders had ongoing responses at the time of analysis. The safety profile was manageable, with the most common treatment-emergent adverse events including rash, fatigue, and hypoalbuminemia, and low rates of treatment discontinuation.
- If further validated, subcutaneous amivantamab could represent a novel targeted treatment option for patients with HPV-unrelated recurrent or metastatic head and neck squamous cell carcinoma whose disease has progressed after platinum-based chemotherapy and immunotherapy.
Based on data from the phase 1b/2 OrigAMI-4 study, the US Food and Drug Administration (FDA) has granted breakthrough therapy designation to amivantamab plus hyaluronidase for patients with HPV-unrelated recurrent or metastatic head and neck squamous cell carcinoma.
In cohort 1 of the study, 67 patients previously treated with platinum-based chemotherapy and a PD-1/PD-L1 inhibitor received subcutaneous amivantamab once every 3 weeks according to body weight (2400 mg for ≤80 kg; 3360 mg for ≥80 kg). The primary end point was objective response rate (ORR). Key secondary end points included duration of response, time to response, clinical benefit rate, and safety.
At a median follow-up of 5.7 months, 32 patients were evaluable for efficacy, and the confirmed ORR was 41%. The median duration of response was 7.2 months, the median time to initial response was 6.4 weeks, and the clinical benefit rate was 88%. Among responders, 85% had ongoing responses and remained on treatment at the time of analysis.
The most common treatment-emergent adverse events occurring in >25% of patients included rash, fatigue, and hypoalbuminemia. Administration-related reactions occurred in 7% of patients, with no grade ≥3 events reported. Treatment-emergent adverse events led to treatment discontinuation in 7% of patients.
“These results represent one of the most encouraging response rates we’ve seen in this difficult-to-treat setting, with durability that could meaningfully extend the time patients live without their disease progressing,” stated primary study investigator Kevin Harrington, MD, PhD, Royal Marsden Hospital, London, United Kingdom.
Sources:
1. PR Newswire. RYBREVANT FASPRO™ (amivantamab and hyaluronidase-lpuj) receives US FDA Breakthrough Therapy Designation for patients with advanced head and neck cancer. Accessed February 18, 2026. https://www.prnewswire.com/news-releases/rybrevant-faspro-amivantamab-and-hyaluronidase-lpuj-receives-us-fda-breakthrough-therapy-designation-for-patients-with-advanced-head-and-neck-cancer-302691112.html
2. Johnson and Johnson. Subcutaneous amivantamab delivers promising 45 percent overall response rate with median duration of 7.2 months in recurrent or metastatic head and neck cancer. Accessed February 18, 2026. https://www.jnj.com/media-center/press-releases/subcutaneous-amivantamab-delivers-promising-45-percent-overall-response-rate-with-median-duration-of-7-2-months-in-recurrent-or-metastatic-head-and-neck-cancer
3. 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. Presented at the 2025 European Society for Medical Oncology (ESMO) Congress; October 17–21, 2025; Berlin, Germany. Abstract 1327MO
