Clinical Summary: 

• Paul Swiecicki, MD, discusses results from cohort 5 of the OrigAMI-4 trial evaluating subcutaneous amivantamab plus pembrolizumab and carboplatin in patients with previously untreated recurrent or metastatic head and neck squamous cell carcinoma.
• The combination demonstrated an overall response rate of 66% among 30 enrolled patients, with a response rate of 77% in HPV-unrelated disease and durable responses reported during ongoing follow-up.
• These preliminary findings support further investigation of amivantamab-based triplet therapy as a first-line treatment strategy for recurrent or metastatic head and neck squamous cell carcinoma, including evaluation in larger studies to establish efficacy, safety, and optimal patient selection.

Paul Swiecicki, MD, University of Michigan, Ann Arbor, Michigan, discusses results from cohort 5 of the OrigAMI-4 trial evaluating subcutaneous amivantamab plus pembrolizumab and carboplatin as first-line treatment for recurrent or metastatic head and neck squamous cell carcinoma. 

Dr Swiecicki reviews the encouraging response rates observed with the triplet, including activity in HPV-unrelated disease, and discusses the durability of responses and preliminary safety findings. He also highlights ongoing investigation of amivantamab-based combinations and their potential to expand first-line treatment options for patients with recurrent or metastatic head and neck cancer. 

Transcript: 

Hi, I'm Paul Swiecicki from the University of Michigan. At ESMO 2026, we're discussing OrigAMI-4, cohort 5, subcutaneous amivantamab, carboplatin, and pembrolizumab in first-line recurrent or metastatic head and neck squamous cell carcinoma.

Cohort 5 of OrigAMI-4 looked at first-line metastatic head and neck cancer. Previously, we had a doublet regarding amivantamab and pembrolizumab presented earlier this year and subsequently published in Clinical Cancer Research, showing a significant response rate and activity in the first-line setting.

This cohort looked at a platinum-sensitive first-line population, ECOG 0 to 1, addition of carboplatin to the regimen. So, subcutaneous amivantamab, pembrolizumab, and carboplatin up to 6 cycles. There's 30 participants enrolled in this cohort, both HPV-positive and HPV-negative, of note. 

We saw that overall the study cohort was positive, with a response rate of 66%. When breaking down specifically to HPV-unrelated versus -related, that is HPV-positive oropharyngeal cancer versus others, this is where the interesting findings started to come out. The response was 77% in those who were HPV-unrelated. Of those, 3 patients had complete responses, and there were quite a few partial responses. We saw all patients had durable responses, and this is ongoing to this day. 

Toxicity was on par with what we would suggest with single-agent activity, and there were no high-grade 3 administration-related reactions. 

Overall, this data is quite promising. There's an ongoing OrigAMI-5 study right now studying the triplet of carboplatin, pembrolizumab, and amivantamab in first-line metastatic head and neck cancer, irrespective of PD-L1. This is very interesting, given some of the other EGFR bispecifics, which are also in the news, but do not have the same trial design. 

In the coming year or two, I think we'll see a brand-new wave of drugs in this space, and hopefully this trial can help guide the space as it moves forward, although not definitive as of now.

Source: 

Swiecicki PLL, Bhatia AK, Brana IG, et al. Amivantamab + pembrolizumab + carboplatin in first-line recurrent/metastatic head and neck squamous cell cancer (1L R/M HNSCC): Results from the phase 1b/2 OrigAMI-4 study. Presented at ESMO Congress. October 23-27, 2026; Madrid, Spain. Abstract 1539RO.