First-Line Amivantamab Plus Pembrolizumab in HPV-Negative Head and Neck Squamous Cell Carcinoma
Key Clinical Summary:
- Design/Population: Cohort 2 of the phase 1b/2 OrigAMI-4 study evaluated subcutaneous amivantamab plus pembrolizumab in 39 patients with previously untreated, HPV-negative recurrent or metastatic head and neck squamous cell carcinoma with PD-L1 CPS ≥1.
- Key Outcomes: The overall response rate was 56%, including a 10% complete response rate, with 82% of patients experiencing tumor shrinkage. Median progression-free survival was 7.7 months, and median overall survival was not reached, with 80% alive at 9 months at data cutoff.
- Clinical Relevance: The combination of subcutaneous amivantamab plus pembrolizumab demonstrated encouraging first-line activity in HPV-negative, PD-L1–positive head and neck squamous cell carcinoma, supporting ongoing evaluation in the phase 3 OrigAMI-5 trial, which will assess this strategy in a broader first-line population irrespective of PD-L1 status.
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 first-line subcutaneous amivantamab plus pembrolizumab in HPV-negative, PD-L1–positive head and neck squamous cell carcinoma.
The combination achieved a 56% overall response rate, with 10% complete responses. Median progression-free survival was 7.7 months, and median overall survival was not reached.
Dr Mehra presented these results at the 2026 Multidisciplinary Head and Neck Cancers Symposium in Palm Desert, California.
Transcript:
Hello, my name is Dr Ranee Mehra, MD. 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.
