Rybrevant-Lazcluze Combo, First Chemotherapy-Free Option for Advanced NSCLC, Approved

Patients with advanced lung cancer have a new, chemotherapy-free option for first-line treatment.

The US Food and Drug Administration (FDA) has approved the combination of Rybrevant (amivantamab-vmjw) and Lazcluze (lazertinib) as a first-line, chemotherapy-free treatment for adult patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) carrying specific epidermal growth factor receptor (EGFR) mutations such as exon 19 deletions or exon 21 L858R substitutions. EGFR mutations are key drivers of NSCLC growth and progression, making targeted therapies like Rybrevant plus Lazcluze a much-needed approval.

The Rybrevant-Lazcluze duo offers a chemotherapy-free approach for adults with limited treatment options. This approval places Rybrevant and Lazcluze in competition with other therapies targeting NSCLC, including AstraZeneca’s Tagrisso (osimertinib) and Roche’s Alecensa (alectinib).

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The approval is based on the results from the Phase III MARIPOSA study, which demonstrated that Rybrevant plus Lazcluze significantly improved progression-free survival (PFS) compared to the current standard of care, osimertinib, outperforming it in terms of PFS and duration of response.

The MARIPOSA study showed a 30 percent reduction in the risk of disease progression or death, with a median PFS of 23.7 months versus 16.6 months for osimertinib. Additionally, the combination therapy extended the time patients could stay on treatment by an additional nine months before their cancer worsened.

Rybrevant is a bispecific antibody that works by targeting the EGFR and MET proteins involved in cancer cell growth. Lazcluze, a tyrosine kinase inhibitor (TKI), is designed to penetrate the brain and specifically target EGFR mutations. Together, they represent a unique multitargeted approach, without the need for chemotherapy.

In addition to the FDA approval, the European Commission recently approved Rybrevant in combination with chemotherapy for patients with advanced NSCLC who have progressed after prior EGFR TKI therapy. This approval was based on MARIPOSA-2 data, which showed a 52 percent reduction in the risk of cancer progression or death compared to chemotherapy alone.

The MARIPOSA study is part of an extensive clinical trial program evaluating the efficacy of Rybrevant in various NSCLC settings. Ongoing and future studies include the Phase III MARIPOSA-2 study that is currently investigating this combination in patients whose cancer has progressed after other treatments. Additionally, the Phase III PAPILLON trial is studying Rybrevant combined with chemotherapy for those with a different EGFR mutation (exon 20 insertions).

Looking ahead, Johnson & Johnson will be presenting at the World Conference on Lung Cancer (WCLC) and the European Society for Medical Oncology (ESMO) 2024 conferences, providing insights into their ongoing investigational solid tumor therapies, particularly in hard-to-treat cancers.