Amivantamab combination posts 77% response rate in advanced head and neck cancer

Overview

Updated 1 hour ago

An experimental Johnson & Johnson combination shrank tumors in 77% of patients with a hard-to-treat form of advanced head and neck cancer, more than double the 36% response rate of the current first-line standard. The results came from 22 patients with HPV-unrelated recurrent or metastatic head and neck squamous cell carcinoma and were presented at the European Society for Medical Oncology congress in Madrid on October 25.

The regimen pairs the bispecific antibody amivantamab with the immunotherapy pembrolizumab and the chemotherapy carboplatin. Amivantamab is the first drug in this setting to dual-target EGFR and MET, the two growth pathways overexpressed in an estimated 80–90% of these tumors. Nearly two-thirds of responses were still ongoing at a median follow-up of 10.6 months, and the combination is now being tested in a global Phase 3 trial.

Why it matters

Patients with HPV-unrelated head and neck cancer could gain a first-line option that roughly doubles their odds of tumor shrinkage, if the Phase 3 trial confirms it.

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Key Indicators

77%

Overall response rate in HPV-unrelated HNSCC

Confirmed responses in 17 of 22 evaluable patients, including 14% complete responses.

36%

Response rate of standard pembrolizumab plus chemotherapy

The first-line benchmark the new combination is measured against, per trial investigators.

65%

Responses ongoing at median 10.6-month follow-up

11 of 17 responders continued to show tumor shrinkage or stable disease at analysis.

Evaluable patients with HPV-unrelated disease

Cohort 5 of the Phase 1b/2 OrigAMI-4 study; 30 patients were dosed in total.

80–90%

HNSCC tumors overexpressing EGFR and MET

Both growth pathways are implicated in tumor progression and treatment resistance.

Voices

Curated perspectives — historical figures and your fellow readers.

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People Involved

ICR and Royal Marsden investigator team

Trial investigators at one of 56 OrigAMI-4 sites across 11 countries

Contributing trial center; presenting co-authors at ESMO 2026

Organizations Involved

Johnson & Johnson

Multinational pharmaceutical company

Developer of subcutaneous amivantamab (RYBREVANT FASPRO); sponsor of OrigAMI-4 and OrigAMI-5 trials

The company developing and testing amivantamab across head and neck cancer and lung cancer settings.

U.S. Food and Drug Administration

Federal regulatory agency

Reviewing later-line amivantamab application under Priority Review; granted Breakthrough Therapy Designation

The U.S. regulator deciding whether subcutaneous amivantamab can be marketed for head and neck cancer.

The Institute of Cancer Research, London

Research institution and NHS cancer center

Trial collaborator and presenter of Cohort 5 results

One of the international centers running the OrigAMI-4 trial in recurrent or metastatic head and neck cancer.

Timeline

2025 October 2026

4 events Latest: Today

Tap a bar to jump to that date

October 2026
First-line combination posts 77% ORR at ESMO 2026
Today Data release

Amivantamab plus pembrolizumab and carboplatin shows 77% confirmed response rate in HPV-unrelated HNSCC, with 65% of responses ongoing.
Today
July 2026
Monotherapy response data confirmed
Data release

Independent review confirmed 42% ORR with 15% complete responses in pretreated metastatic HNSCC patients.
July 8th, 2026
February 2026
FDA grants Breakthrough Therapy Designation
Regulatory

Designation covers amivantamab monotherapy in HPV-unrelated recurrent or metastatic HNSCC after prior platinum and immunotherapy.
February 18th, 2026
2025
Monotherapy data presented at ESMO 2025
Data release

OrigAMI-4 Cohort 1 showed rapid, durable responses with single-agent amivantamab in heavily pretreated HNSCC patients.
2025

Scenarios

FDA approves amivantamab monotherapy for later-line head and neck cancer

Likely Resolves by Q2 2027

Discussed by: Johnson & Johnson press materials citing the application under Priority Review

The FDA is reviewing subcutaneous amivantamab alone for patients with HPV-unrelated recurrent or metastatic HNSCC who have already progressed on platinum chemotherapy and a PD-1/PD-L1 inhibitor. The February 2026 Breakthrough Therapy Designation signals FDA interest, and Priority Review typically brings a decision within about six months of acceptance. An approval would give a heavily pretreated group with few options a new standard later-line therapy.

Phase 3 OrigAMI-5 confirms the first-line benefit

Possible Resolves by End of 2028

Discussed by: ICR London and Royal Marsden investigators who advocated moving the regimen forward

OrigAMI-5 is comparing amivantamab plus pembrolizumab and carboplatin against the standard of pembrolizumab, a platinum drug, and fluorouracil in first-line HPV-unrelated disease. If the 77% response rate holds across a larger population and the trial meets its survival or progression-free survival endpoint, the combination could replace the current standard of care in the first-line setting.

Phase 3 trial fails to confirm the early signal

Unlikely Resolves by End of 2028

Discussed by: Trial observers noting the 77% figure rests on just 22 patients

Response rates from small cohorts often fall as trials broaden to larger, more diverse populations. If OrigAMI-5 misses its endpoint, the first-line program stalls and the combination remains unproven outside the original Cohort 5 group, while the later-line monotherapy application and any approved use would be unaffected.

Historical Context

3 moments from history that rhyme with this story — and how they unfolded.

2006

Cetuximab (Erbitux) approval for head and neck cancer (2006)

The FDA approved cetuximab, the first EGFR-blocking antibody, for head and neck cancer in 2006. It showed modest response rates when used alone in recurrent or metastatic disease, and its main benefit came as an addition to radiation or chemotherapy.

Then

Cetuximab became a standard addition to radiation and chemo for locally advanced disease, but single-pathway blockade left most patients without a response.

Now

The drug proved the EGFR pathway is a valid target in HNSCC, setting the stage for combination approaches.

Why this matters now

Amivantamab also blocks EGFR but adds a second target, MET, aiming to overcome the resistance that limited single-pathway drugs like cetuximab.

2019

KEYNOTE-048 trial (2019)

The KEYNOTE-048 trial established pembrolizumab plus chemotherapy as the first-line standard for recurrent or metastatic head and neck squamous cell carcinoma. It reported an objective response rate around 36% and improved overall survival in PD-L1-positive tumors.

Then

Pembrolizumab plus chemo became the global first-line benchmark for this patient group.

Now

The roughly 36% response rate has stood as the bar newer regimens must clear.

Why this matters now

The amivantamab combination's 77% response rate is measured against this pembrolizumab-plus-chemo benchmark in the same first-line setting.

2021–2024

Amivantamab in EGFR-mutated lung cancer (2021–2024)

Amivantamab was first approved in May 2021 for EGFR-mutated non-small cell lung cancer, and later trials including MARIPOSA validated its dual EGFR-MET targeting in earlier treatment lines.

Then

The drug became a standard option across lung cancer settings, building a safety and efficacy record in thousands of patients.

Now

The same dual-targeting mechanism is now being carried into head and neck cancer, where EGFR and MET are overexpressed in most tumors.

Why this matters now

Amivantamab's lung cancer approvals are the foundation the HNSCC program draws on, giving regulators and investigators years of real-world data.