ESMO 2025 | OrigAMI-4: amivantamab monotherapy in previously treated R/M HNSCC

Amivantimab is a bispecific antibody that targets both EGFR and C-MET. The rationale for developing amivantimab in patients with relapsed and metastatic head and neck cancer is that the disease often overexpresses both EGFR and MET, and MET can be an escape pathway to allow tumor cells to become resistant to EGFR blockade. So a bispecific antibody targeting both of those moieties is potentially going to prevent that resistance emerging. Amivantimab has a third mechanism of action whereby the FC portion of the antibody can recruit anti-tumor immune responses. So the Origami 4 Cohort 1 study of single-agent amivantimab given by a three-weekly subcutaneous schedule in HPV-unrelated disease in patients who had previously been exposed both to immune checkpoint blockade and platin chemotherapy, so a classical second or third line setting. We treated patients with subcutaneous amivantimab, and we documented data from two populations that were reported. There were 86 patients who had received at least one dose of amivantimab who represent the safety population. And there were a further 38 patients who had undergone at least two response assessments or had discontinued the drug for any reason. And they represent the efficacy evaluable population. So in terms of safety, we see that the drug causes the typical side effects that we expect from both EGFR blockade and C-MET blockade. So skin and nail changes, hypomagnesemia attributable to the EGFR blockade, peripheral edema and hypoalbuminemia attributable to the MET blockade. All of those side effects were manageable. Very few were grade three. We also saw the infusion-related reaction rate was only 7% in this study with the subcutaneous formulation, which is less than what we see with intravenous administration. And none of those reactions was greater than grade two. So this is a step forward in the use of this drug in the clinic. When we turn to the data for efficacy, we see that the overall response rate to amivantimab in this context was 45%. And a further 45% of patients had stable disease. This is a remarkably strong signal for this drug in this setting of second and third line both immune checkpoint and platin refractory patients. We saw that a number of the patients who had a response were continuing on treatment indeed more than half of the patients at the time of the analysis. We also saw that for the responding patients the median duration of response was greater than seven months and for the efficacy evaluable population the median progression free survival is 6.8 months and the overall survival median has not yet been reached so taken together these data show that amivantimab by this subcutaneous three-weekly schedule is both safe and efficacious. And on the back of this, a decision has been taken to move this agent into the frontline setting to combine it with pembrolizumab and platinum chemotherapy in a randomized phase three study where the comparator arm will be chemotherapy plus pembrolizumab from the keynote 048 trial that was published in 2019.

This transcript is AI-generated. While we strive for accuracy, please verify this copy with the video.