OrigAMI-4 Demonstrates Encouraging Activity of Subcutaneous Amivantamab Plus Pembrolizumab in HPV-Negative Head and Neck Cancer
Clinical Summary:
- Design/Population: Cohort 2 of the phase 1b/2 OrigAMI-4 study evaluated subcutaneous amivantamab plus pembrolizumab as first-line treatment in 39 patients with recurrent or metastatic HPV-negative head and neck squamous cell carcinoma and a PD-L1 combined positive score (CPS) ≥1.
- Key Outcomes: The combination demonstrated encouraging antitumor activity, with a high overall response rate, substantial tumor shrinkage, and promising progression-free survival. The safety profile supported continued clinical development of the regimen in the frontline setting.
- Clinical Relevance: These findings support further evaluation of subcutaneous amivantamab plus pembrolizumab as a first-line treatment strategy for HPV-negative head and neck squamous cell carcinoma and provide the rationale for the ongoing phase 3 OrigAMI-5 trial.
Ranee Mehra, MD, University of Maryland Greenebaum Comprehensive Cancer Center, Baltimore, Maryland, discusses results from cohort 2 of the phase 1b/2 OrigAMI-4 study evaluating subcutaneous amivantamab plus pembrolizumab in patients with recurrent or metastatic HPV-negative head and neck squamous cell carcinoma.
The study demonstrated encouraging clinical activity in the frontline setting, with durable tumor responses and promising early survival outcomes. These findings provide the foundation for the ongoing phase 3 OrigAMI-5 trial evaluating amivantamab-based therapy in combination with chemotherapy and pembrolizumab for patients with recurrent or metastatic HPV-negative head and neck cancer.
Dr Mehra presented these results at the Multidisciplinary Head and Neck Cancers Symposium in Palm Desert, California.
Transcript:
Hello, my name is Dr Ranee Mehra. I'm a medical oncologist at the University of Maryland Greenebaum Comprehensive Cancer Center, where I'm solid tumor section head and associate director for clinical research.
Today I want to talk about the results that were recently presented at the Multidisciplinary Head and Neck Cancers Symposium, which focused on cohort 2 of OrigAMI-4, which is a phase 1b/2 study of the combination of subcutaneous amivantamab with pembrolizumab for patients with head and neck squamous cell carcinoma. Cohort 2 focused on the first-line treatment of patients who were HPV-negative and who had a PD-L1 CPS score ≥1.
In this study, 39 patients were enrolled and treated with the combination of subcutaneous amivantamab plus pembrolizumab. The primary end point was overall response rate, and this was found to be 56%. There was a 10% complete response rate, but 82% of patients had some degree of tumor shrinkage. This resulted in a median progression-free survival of 7.7 months, and the median overall survival was not reached, but 80% were alive at 9 months at the time of the data cutoff.
These are preliminary results in the first line setting for this combination but does pose a new treatment option for further study. There is a currently enrolling first line trial OrigAMI-5, which is looking at the combination of carboplatin plus amivantamab and pembrolizumab. The goal for this randomized phase 3 study is to look at this combination in the first-line recurrent metastatic setting for HPV-negative disease, irrespective of PD-L1 status.
Source:
Mehra R, Kao HF, Sandhu MS, et al. Amivantamab Plus Pembrolizumab in Previously Untreated Recurrent/Metastatic Head & Neck Squamous Cell Cancer: Results From the Phase 1b/2 OrigAMI-4 Study. Presented at Multidisciplinary Head and Neck Cancers Symposium. February 19 - 21, 2026. Palm Desert, California. Abstract 2.
