J&J’s Rybrevant-Lazcluze combination wins FDA first in lung cancer

The US Food and Drug Administration (FDA) has approved the first subcutaneous therapy for epidermal growth factor receptor (EGFR)-mutated non-small cell lung cancer (NSCLC).

The Johnson & Johnson combination treatment brings together its first-in-class bispecific antibody Rybrevant Faspro (amivantamab and hyaluronidase-lpuj) with the small molecule Lazcluze (lazertinib).

The benefit of this therapeutic approach is that it can be given to patients in just minutes instead of hours and reduces administration-related reactions by five-fold.

Additionally Rybrevant and Lazcluze not only engages the immune system but also inhibit MET gene alterations, which could change the natural history of the disease by reducing the spectrum and complexity of acquired resistance mechanisms, J&J highlighted.

The approval is based on the results from the phase III PALOMA-3 study. Findings from the subcutaneous arm showed longer duration of response, improved progression-free survival and longer overall survival compared to the intravenous arm. For example, at 12 months, 65 percent of patients given subcutaneous treatment were still alive, compared with 51 percent of those treated intravenously.

Data was presented at the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting and published in the Journal of Clinical Oncology. 

Joelle Fathi, Chief Healthcare Delivery Officer at GO2 for Lung Cancer, said: “Patients now have a simple, chemotherapy-free frontline option that not only targets the disease more precisely but also significantly improves survival.”

The FDA’s latest approval offers an important new therapeutic option considering that resistance to third-generation tyrosine kinase inhibitors (TKIs), such as osimertinib remains a major barrier to long-term disease control, according to an updated analysis from the Mariposa study.

Dr Danny Nguyen, principal investigator for the phase III PALOMA-3 and Mariposa studies, said: “The combination of Rybrevant plus Lazcluze changes the biology of the disease by preventing resistance and delivers unmatched overall survival in the first-line setting, while omitting chemotherapy from treatment.

“We have an entirely new subcutaneous therapy that offers consistent results compared to intravenous delivery, while providing a more patient-centred experience.”

This milestone builds on promising data from the Mariposa study showing unmatched overall survival benefit of Rybrevant Faspro plus Lazcluze, projected to last beyond four years.

Rybrevant is already approved in the US across four indications in EGFR-mutated NSCLC, in both first- and second-line settings.