J&J's amivantamab hits 77% response rate in first-line HNSCC trial

Johnson & Johnson has reported a 77% overall response rate for subcutaneous amivantamab in combination with pembrolizumab and carboplatin as a first-line treatment for patients with recurrent or metastatic head and neck squamous cell carcinoma (HNSCC) that is not HPV-associated. The data, drawn from Cohort 5 of the Phase 1b/2 OrigAMI-4 study, were presented as a rapid oral session at the European Society for Medical Oncology Congress in Madrid on 25 October 2026.

Among 22 evaluable patients with HPV-unassociated HNSCC, the confirmed response rate of 77% (95% CI, 55–92) included complete responses in 14% and partial responses in 64%. Tumour shrinkage was observed in all evaluable patients, and 65% of responses remained ongoing at a median follow-up of 10.6 months. Median overall survival was not reached, and 77% of patients were alive at one year. The seven patients with HPV-associated oropharyngeal disease showed a markedly lower response rate of 29%, consistent with the known biology of EGFR-targeted bispecifics in this molecularly distinct subgroup.

Trial design and safety

Thirty patients in Cohort 5 received subcutaneous amivantamab administered every three weeks alongside pembrolizumab and up to six cycles of carboplatin; 29 were included in the efficacy analysis. The primary endpoint was investigator-assessed overall response rate by RECIST v1.1. Administration time for the subcutaneous formulation was reported at five minutes or less, a logistical advantage over intravenous delivery that Johnson & Johnson has previously highlighted in its NSCLC programme.

The safety profile was described as consistent with the known profiles of the individual agents. The most common adverse events were anaemia (73%), hypoalbuminaemia (63%), thrombocytopenia (63%) and stomatitis (57%). Administration-related reactions occurred in 13% of patients, with no Grade 3 or higher events recorded for that category.

Yusri Elsayed, Global Therapeutic Area Head for Oncology at Johnson & Johnson, said experience with amivantamab in lung cancer had helped to "establish the potential of dual EGFR/MET targeting," adding that the new results supported continued evaluation in head and neck cancer.

Market context and competitive landscape

HNSCC represents approximately 4.5% of all cancers worldwide. Around 75% of cases are HPV-unassociated and carry a worse prognosis, and nearly 60% of patients with recurrent or metastatic disease do not receive subsequent treatment after first-line failure. The current standard of care is largely built on the KEYNOTE-048 regimen of pembrolizumab with or without chemotherapy, approved on the basis of PD-L1 combined positive score. Response rates with that regimen in unselected populations typically fall in the 35–40% range, giving the OrigAMI-4 numbers notable context, though any cross-trial comparison is confounded by patient selection and PD-L1 enrichment in Cohort 5.

Amivantamab targets both EGFR and MET, two receptor tyrosine kinases implicated in tumour growth and acquired resistance in 80–90% of HNSCC tumours. In NSCLC the drug already holds European Commission approval across four indications. A small number of other bispecifics and antibody-based combinations targeting EGFR or MET are in earlier development for HNSCC, though none has reached pivotal-stage readout in the first-line setting.

The pivotal Phase 3 OrigAMI-5 study is now ongoing, and its readout will be the critical inflection point for the programme. Investigators and investors will look for overall survival data and durability metrics from that trial before drawing firm conclusions about amivantamab's commercial and clinical positioning against pembrolizumab-based standards.