SINGAPORE – The US Food and Drug Administration (FDA) has granted accelerated approval for the oral drug sevabertinib for the treatment of adults with non-squamous, non-small-cell lung cancer (NSCLC) whose tumours have specific gene mutations.

This was after early-phase clinical trials – which involved centres worldwide, including the National Cancer Centre Singapore (NCCS) – showed that the drug can shrink tumours in patients whose cancer had not responded to other treatments.

The human epidermal growth factor receptor 2 (HER2) is a protein found on the surface of cells that control cell growth.

Mutations of the HER2 gene in cancer cells can keep the cells permanently “switched on”, driving them to multiply rapidly and form aggressive tumours. This affects between 1 per cent and 3 per cent of NSCLC cases in the US and Europe, and between 1.4 per cent and 6.7 per cent of cases in Asia.

The twice-daily oral drug received FDA approval in November before Phase 3 trials, giving patients with locally advanced or metastatic cancer who had previous systemic treatments, such as chemotherapy or targeted therapy, earlier access to the drug.

Sevabertinib is marketed by Bayer under the brand name Hyrnuo. Among patients who had not received previous HER2-targeted therapy, sevabertinib shrank tumours in 71 per cent of the cases, with the effect typically lasting about nine months. In more than half of patients, the drug kept tumours smaller for at least six months.

Of patients who had received HER2-targeted therapy, the drug shrank tumours in 38 per cent of them, with the effect typically lasting about seven months. In more than half of these patients, tumours remained smaller for at least five months.

“More importantly, the safety profile was manageable, with most patients able to continue treatment,” said Professor Daniel Tan, head of clinical trials and epidemiological sciences division at NCCS, who led the Singapore study.

Treatment had to be stopped in just 3 per cent of the cases due to adverse effects. Serious side effects occurred in 31 per cent of patients – most commonly diarrhoea, which affected about nine in 10 patients.

The findings of the clinical trials were published in the peer-reviewed New England Journal Of Medicine on Oct 17.

NCCS recruited a cohort of 209 patients for the studies.

“While running this trial, it provided patients with good options for HER2-targeted therapy as an oral tablet... This gives us great hope in our efforts to improve outcomes for this patient population, which was challenging to treat effectively,” Prof Tan said.

Lung cancer is the deadliest cancer, with around 1.8 million deaths annually. It is primarily driven by smoking.

But in Singapore, unlike in the West, half of lung cancer patients have never smoked. Furthermore, a disproportionate number of female non-smokers are diagnosed with NSCLC, which occurs in both smokers and non-smokers.

The first lung cancer screening research study here conducted in 2022 picked up cancerous lung nodules in nine out of the more than 530 participants screened. All of them are non-smokers and had Stage 1 lung cancer.

Prof Tan said Phase 3 trials for sevabertinib are still needed for full approval by FDA.

He noted that not all new cancer drugs are on Singapore’s Cancer Drug List, which names outpatient treatments whose cost may be partly claimed through MediShield Life or MediSave. Some drugs on the list are subsidised.

The list, however, is not static, and will be updated as treatments are reviewed, he added.