OrigAMI-5 is a clinical trial that is seeking to understand whether or not amivantamab has a role in first-line therapy of recurrent metastatic head and neck cancer. The setting here is that we know historically that if a tumour is PD-L1 expressing that pembrolizumab monotherapy or pembrolizumab plus chemotherapy is superior to older treatments of chemotherapy with an EGFR inhibitor. Amivantamab is an EGFR inhibitor but it’s a bispecific and it also addresses MET, which is a common source of resistance to EGFR inhibition. We also know that for all comers, irrespective of PD-L1 expression, that pembrolizumab plus chemotherapy is effective therapy and has been accepted as the appropriate first-line treatment for patients independent of their PD-L1 expression.

Some patients prefer to receive pembrolizumab monotherapy and not to receive pembrolizumab in combination with chemotherapy but we understand that pembrolizumab plus chemotherapy has higher objective response rates. So, for the many patients with head and neck cancer who are symptomatic, where there is a requirement for high doses of pain medication, where there’s a risk of bleeding, a risk of impairment to the airway, inability to swallow and dependence on a feeding tube, where lesions in the lung threaten to lead to obstructive pneumonia, in all of these cases a higher response rate is desirable. It’s also the case that for patients with low PD-L1 expression pembrolizumab plus chemotherapy may be superior.

For this reason this trial looks at incorporating amivantamab into the pembrolizumab plus chemotherapy backbone. So the control arm is pembrolizumab plus doublet chemotherapy of 5FU and a platinating agent, as was the winning arm of KEYNOTE-048. The investigational arm takes the same chemotherapy drugs, carboplatin, the same immunotherapy, pembrolizumab, but it substitutes the EGFR/MET bispecific for the second chemo drug, 5FU. So the co-primary endpoints here depend a little bit on region of the world but, basically, objective response rate and overall survival. There’s an approach to managing the skin rash that can result from amivantamab; amivantamab is given subcutaneously so the risk of high-grade infusion reactions doesn’t seem to be an issue. We’re hoping that this is going to read out and show us whether or not amivantamab has a role in the first line.

What is next?

The OrigAMI-5 trial is ongoing and for patients who have recurrent metastatic HPV-negative head and neck cancer, independent of their PD-L1 expression, enrolment on that trial is a very good option.