Dr Mehra on the FDA Breakthrough Therapy Designation for Amivantamab in HNSCC

“These are exciting data because they give us a potential future treatment option for these patients and allow for the development of this drug in the recurrent setting for patients who’ve received prior treatment.”

Ranee Mehra, MD, director of Head and Neck Medical Oncology and a professor of medicine at the Marlene and Stewart Greenebaum Comprehensive Cancer Center at the University of Maryland Medical System, discussed data that supported the February 20, 2026 FDA breakthrough therapy designation for amivantamab and hyaluronidase-lpuj (Rybrevant Faspro; subcutaneous amivantamab) for the treatment of adult patients with recurrent or metastatic, human papillomavirus–unrelated head and neck squamous cell carcinoma (HNSCC) who have progressive disease during or after treatment with platinum-based chemotherapy and a PD-L1 or PD-1 inhibitor.

Mehra detailed findings from cohort 1 of the phase 1/2 OrigAMI-4 trial (NCT06385080), which served as the primary foundation for the breakthrough therapy designation. She argued that for patients with recurrent or metastatic HNSCC who have already progressed after receiving platinum-based chemotherapy and checkpoint inhibitors, current standard treatment options are critically limited.

To address these challenges, the study evaluated subcutaneous amivantamab in patients with recurrent or metstatic HSNCC. Amivantamab is an EGFR-MET bispecific antibody with a unique triple mechanism of action. Beyond inhibiting the EGFR and MET pathways—the latter of which functions as a key escape pathway for tumors—the drug engages in immune cell-directing activity.

In OrigAMI-4, amivantamab was administered via a subcutaneous formulation coformulated with recombinant human hyaluronidase PH20, which resulted in a low rate of administration-related reactions of 7%, all of which were grade 1 or 2. The safety population for this clinical initiative included 86 patients with a median age of 63.5 years (range, 30-81), all of whom had previously received both immunotherapy and platinum-based chemotherapy.

The efficacy data, as highlighted by Mehra, demonstrated a significant overall response rate of 45% (95% CI, 29%-62%) within the evaluable population (n = 38). Additionally, 82% of patients experienced tumor shrinkage of target lesions. The clinical benefit rate was 76% (95% CI, 60%-89%), and the median time to first response was 6.4 weeks. Furthermore, the antitumor responses proved durable, with a median duration of response of 7.2 months (95% CI, 5.3-not evaluable) and a median progression-free survival of 6.8 months (95% CI, 4.2-9.0).