OrigAMI-4 is a multi-cohort study that looks at the EGFR/MET bispecific antibody in head and neck cancer. It has multiple cohorts, some focused on recurrent metastatic disease, some focused actually on the locally resectable disease. At ASCO this year we presented the full results from cohort 1. This looked at amivantamab monotherapy in patients with prior immunotherapy and chemotherapy treatment and it evaluated objective response, progression free survival and overall survival.

There were 102 patients, 100% of them had previously received platinum-based chemotherapy and an immune checkpoint inhibitor; 48% of them had actually received two lines of prior therapy. In this study we saw a response rate as adjudicated by a blinded independent central review of 42%. This was confirmed by investigators with an investigator assessed response rate of 47%.

According to blinded independent central review, the complete response rate was 15%. The median progression free survival was quite favourable for a population of this line of therapy, this heavily pretreated, and the overall survival was 12.5 months. If you compare the overall survival here to a similarly heavily pretreated patient population treated with the EGFR inhibitor cetuximab in the INTERLINK trials, here the median overall survival of 12. 5 months compares very favourably to 8.6 months with cetuximab monotherapy.

Overall, safety looked quite good. The majority of the toxicities were grade 1 or 2. There was about a 15% rate of administration-related reactions but in this trial amivantamab was used in the subcutaneous formulation and then had zero grade 3 or higher administration-related reactions. There was one treatment-related death due to pneumonitis and there were five other patients who died on study but in this heavily pretreated population that seemed on a par with previous experience.

So the overall conclusion is that amivantamab is highly active in previously treated, HPV negative, head and neck cancer with a high response rate, good progression free survival, good overall survival and very favourable toxicity. The results were simultaneously published in The Journal of Clinical Oncology and have been submitted to the FDA.

What impact could these findings have?

We’ll see what the FDA decides but we do not have other agents that have single-agent activity in this range that are safe, tolerable and have durable responses. So I anticipate that this will enter the armamentarium. It’s also the case that with this high activity and the results of another cohort in this study, cohort 2 that looked at amivantamab plus pembrolizumab in the first-line setting where the response rate was 56% and similarly it was highly tolerable, we’re also very interested in studying this in the first line.