ESMO 2026: New treatment combination shows promising results in recurrent head and neck cancer
A treatment combination including the targeted therapy amivantamab shrank tumours in more than three-quarters of patients with a hard-to-treat form of recurrent and/or metastatic head and neck cancer, according to results from an international clinical trial.
Researchers from The Institute of Cancer Research, London, and The Royal Marsden NHS Foundation Trust took part in the global study, which found that amivantamab, given alongside the immunotherapy pembrolizumab and chemotherapy, achieved tumour responses in 77 per cent of patients with HPV-unrelated recurrent and/or metastatic head and neck squamous cell carcinoma (HNSCC).
The findings, which were presented today at the European Society for Medical Oncology (ESMO) Congress 2026 in Madrid, are particularly encouraging because the current first-line treatment of pembrolizumab plus chemotherapy shrinks tumours in 36 per cent of patients with recurrent and/or metastatic head and neck cancer.
The results come from Cohort 5 of the international OrigAMI-4 clinical trial, which is being conducted at 56 sites across 11 countries and is evaluating amivantamab both on its own and in combination with other treatments.
In earlier cohorts, investigators saw that tumours shrank in 42 per cent of patients treated with amivantamab alone and 56 per cent with amivantamab plus pembrolizumab.
Head and neck squamous cell carcinoma is the most common type of head and neck cancer. Patients whose cancer has spread to other parts of the body or returned after treatment often face poor outcomes, and many do not benefit from existing therapies.
Head and neck cancers can broadly be divided into HPV-related and HPV-unrelated disease. HPV-related cancers are caused by infection with human papillomavirus and generally have better outcomes. HPV-unrelated cancers are typically harder to treat and associated with poorer survival.
Researchers have been investigating whether amivantamab, a bispecific antibody that targets the cancer-driving proteins EGFR and MET, can improve outcomes for these patients.
Cohort 5 of the Phase Ib/II OrigAMI-4 study evaluated amivantamab in combination with pembrolizumab and chemotherapy as a first-line treatment for recurrent and/or metastatic disease in patients whose tumours expressed PD-L1.
In total, 30 patients received treatment and 29 were included in the analysis.
Among 22 patients with HPV-unrelated disease, 17 achieved a confirmed response, resulting in an objective response rate of 77 per cent. Three patients achieved a complete response, meaning no detectable cancer remained, while 14 achieved a partial response.
Four patients had stable disease and one experienced disease progression. At the time of analysis, 11 of the 17 patients who responded to treatment continued to see their tumour shrink or remain stable.
Among seven patients with HPV-positive oropharyngeal squamous cell carcinoma, two achieved a partial response, giving an objective response rate of 29 per cent.
The findings have led investigators to take this regimen forward into the global Phase III OrigAMI-5 study, which is comparing amivantamab, pembrolizumab and chemotherapy with standard treatment in patients with HPV-unrelated recurrent and/or metastatic HNSCC.
Professor Kevin Harrington, Professor of Biological Cancer Therapies at The Institute of Cancer Research, London, and Consultant Clinical Oncologist at The Royal Marsden NHS Foundation Trust, said:
“These findings are particularly encouraging because the strongest activity was seen in patients with HPV-unrelated disease, who typically have poorer outcomes and fewer effective treatment options than patients with HPV-related cancers.
“We observed tumour responses in 77 per cent of patients in this group. Current pembrolizumab-based chemotherapy has achieved response rates of around 36 per cent, so this level of activity is very exciting.
“The decision to take this regimen forward into a global Phase III trial reflects the confidence these results have given us and provides an important opportunity to determine whether it can improve outcomes for patients.”
Professor Kristian Helin, Chief Executive of The Institute of Cancer Research, London, said:
"For years, head and neck cancer has been treated largely as one disease, even though HPV-related and HPV-unrelated tumours behave very differently. These results suggest we can do better by treating the biology. In this case, that means hitting the EGFR and MET signals that HPV-unrelated tumours rely on, while also helping the immune system attack the cancer.
“The numbers are still small, and the Phase III trial will be the real test. But this is the kind of rational, biology-driven drug combination that we believe will transform outcomes for patients with hard-to-treat cancers."
Royal Marsden patient Holly Stubbs, 29, from County Durham, was diagnosed with stage one tongue cancer in April 2025, while pregnant with her third child. She underwent surgery to remove part of her tongue during pregnancy, followed by surgery to remove lymph nodes in her neck and six weeks of radiotherapy after giving birth. However, a year later, her cancer returned, and she was told it was incurable.
Holly said: “When I was told my cancer was incurable and that there were no other treatment options available to me at my local hospital, I was desperate to find another way forward. I contacted Professor Harrington at The Royal Marsden, whose open-minded approach and extensive knowledge gave me hope and made me excited about the possibility of joining the OrigAMI-5 trial. I started the triple-combination treatment in July.”
“Scans have already shown a 60 per cent reduction in my cancer and the intense pain I was previously experiencing disappeared within the first few weeks of starting treatment.
“As a mum of three young children, being given another treatment option has meant everything to me. When I thought there was nothing else that could be done, the trial gave me hope.”
Source: The Institute of Cancer Research