Fifteen patients saw their tumours vanish entirely after receiving a new triple-action cancer injection, in results doctors have described as unprecedented. The jab, amivantamab, shrank or eliminated tumours in more than a third of participants in an international trial, with some patients seeing dramatic changes within weeks of starting treatment.
The study involved 102 patients with head and neck cancer – the world’s sixth most common cancer – across 11 countries. All had advanced disease that had spread or returned, and had failed to respond to both chemotherapy and immunotherapy. Researchers found that 43 patients responded to the drug: 28 saw significant tumour shrinkage, and in 15 the tumours were completely eradicated. Crucially, the trial focused on patients whose cancers were not caused by the human papillomavirus (HPV), a group known to be far harder to treat and with poorer outcomes. Those receiving amivantamab lived for a median of 12.5 months after starting the drug, a notable survival figure given the limited options once standard treatments stop working.
How the triple-action jab works
Amivantamab, developed by Johnson & Johnson and also known by the brand name Rybrevant, is a bispecific antibody – a type of smart drug that targets cancer cells in three distinct ways. First, it blocks a protein called EGFR (epidermal growth factor receptor), which sits on the surface of many cancer cells and drives their growth. Second, it blocks the MET pathway, a signalling route that cancer cells often hijack to escape the effects of other treatments. By hitting both targets at once, the jab attacks the tumour directly while closing off one of its main escape routes. Third, amivantamab activates the patient’s own immune system, recruiting immune cells to attack the tumour through a process known as antibody-dependent cellular cytotoxicity (ADCC). It can also lead to the degradation of the EGFR and MET receptors themselves, further weakening the cancer’s ability to survive.
Professor Kevin Harrington, professor of biological cancer therapies at the Institute of Cancer Research, London (ICR), and a consultant oncologist at the Royal Marsden NHS Foundation Trust, said: “These are unprecedentedly strong responses in patients whose disease has become resistant to both chemotherapy and immunotherapy. This is a group of patients for whom treatment options are extremely limited, so seeing this level of benefit is very striking.” He added that the treatment “has the potential to benefit many thousands of patients each year”.
The results were presented at the world’s largest cancer conference, the annual meeting of the American Society of Clinical Oncology (Asco), in Chicago.
Administration and side effects
Unlike many cancer therapies that require an intravenous drip, amivantamab is given as a tiny injection under the skin, making it quicker and more convenient for patients and easier to deliver in outpatient clinics. The jab is administered once every three weeks. Side effects were mostly mild to moderate, with fewer than one in ten patients forced to stop treatment. Common side effects included rash, infected skin around the nails (paronychia), nausea, fatigue, mouth sores, and changes in liver enzymes. Serious side effects such as severe skin reactions or lung inflammation were rare.
Patient experience: ‘The thing I enjoyed most was the first big steak’
One of the first patients to benefit was Carl Walsh, 56, from Birmingham, who was diagnosed with tongue cancer in May 2024. After chemotherapy and immunotherapy failed, he joined the OrigAMI-4 trial at the Royal Marsden in July 2025. “I now feel able to live a normal life,” he said. “Before starting the trial, I struggled to speak properly and found eating difficult because of the swelling and pain. Since beginning treatment, the swelling has reduced significantly, and my pain levels have improved considerably.” He added that he no longer experienced the same life-impacting side effects he had during chemotherapy. “When things were at their worst I was eating soup, rice pudding, tins of ravioli and spaghetti and many, many omelettes, all augmented by three prescribed nutritional milk drinks a day. I lost quite a bit of weight. After only two cycles of the treatment my diet started to return to normal and I was eating a full diet after six months. The thing I enjoyed most was the first big steak. My speech is completely back to normal and at work I speak regularly on headsets without problems.” Walsh is now on his 17th cycle of treatment.
Broader research and regulatory progress
Beyond head and neck cancer, amivantamab is being evaluated in around 60 clinical trials, primarily for lung cancer but also for colorectal, brain and gastric cancers. It has already received accelerated approval from the US Food and Drug Administration (FDA) for certain types of advanced non-small cell lung cancer (NSCLC) with EGFR exon 20 insertion mutations. The FDA has also granted breakthrough therapy designation for subcutaneous amivantamab as a monotherapy for patients with HPV-unrelated recurrent or metastatic head and neck cancer who have already received platinum-based chemotherapy and PD-1/PD-L1 immunotherapy.
The OrigAMI-4 trial, which produced the latest results, is a Phase 1b/2 study. Preliminary data from the monotherapy part of the trial showed an overall response rate of 45%, with a median duration of response of 7.2 months. Another cohort combining amivantamab with the immunotherapy pembrolizumab achieved a 56% response rate in first-line treatment for advanced HPV-unrelated, PD-L1-positive head and neck cancer. A larger Phase 3 trial, OrigAMI-5, is now under way, evaluating the subcutaneous jab alongside chemotherapy and pembrolizumab as a first-line treatment for the same patient group. In lung cancer, the PAPILLON trial demonstrated significant benefit when amivantamab was combined with carboplatin-pemetrexed in the first-line setting, with a median progression-free survival of 11.4 months, while the CHRYSALIS-2 study is assessing it in combination with lazertinib. For colorectal cancer, the OrigAMI-1 study showed a 51% overall response rate when amivantamab was given with chemotherapy, with a median duration of response of 9.3 months.
Professor Kristian Helin, chief executive of the ICR, said: “This study demonstrates how the development of new treatments through rigorous cancer research may lead to meaningful advances, even for patients with very limited treatment options. Achieving this level of tumour response and encouraging survival outcomes in such a challenging‑to‑treat group represents a significant step forward.”
