Dr Mehra on the Efficacy of Subcutaneous Amivantamab Plus Pembrolizumab in HNSCC

“We’re seeing the activity of [subcutaneous amivantamab] as monotherapy and in combination [regimens] now in different lines of therapy for head and neck cancer.”

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 with amivantamab and hyaluronidase-lpuj (Rybrevant Faspro; subcutaneous amivantamab) plus pembrolizumab (Keytruda) from cohort 2 of the phase 1/2 OrigAMI-4 trial (NCT06385080) in patients with first-line recurrent or metastatic head and neck squamous cell carcinoma (HNSCC).

She noted that initial data from cohort 1 of OrigAMI-4 presented at the 2025 ESMO Congress showed an overall response rate (ORR) of 45% (95% CI, 29%-62%) with subcutaneous amivantamab as monotherapy among efficacy-evaluable patients with recurrent or metastatic, human papillomavirus (HPV)–unrelated HNSCC who had not received prior EGFR-directed therapy (n = 38). This evidence served as a precursor for the more recent data from the study that Mehra and colleagues presented at the 2026 Multidisciplinary Head and Neck Cancers Symposium.

During her presentation, Mehra highlighted results from cohort 2, which evaluated subcutaneous amivantamab plus pembrolizumab in patients with treatment-naive, HPV-unrelated, recurrent or metastatic HNSCC (n = 39). The ORR was 56% (95% CI, 40%-72%), including 6 complete responses, 4 of which were confirmed at the time of analysis. Additionally, 18 partial responses were reported, all of which were confirmed. At a median follow-up of 10.4 months (range, 1.6-12.5), 46% of patients in this arm were still receiving the study treatment. Additionally, the rate of tumor shrinkage of target lesions was 82%.

Ultimately, Mehra stated that the clinical evidence points to the versatility of subcutaneous amivantamab across lines of therapy for patients with HNSCC. She concluded that the agent has shown significant activity both as a monotherapy and in combination with other therapies.