FDA Approves J&J's Rybrevant/Lazcluze for First-Line Lung Cancer Treatment

Johnson & Johnson’s (J&J) Rybrevant (amivantamab-vmjw) and Lazcluze (lazertinib) have gained approval from the US Food and Drug Administration (FDA) as a first-line treatment for adults with non-small cell lung cancer (NSCLC). This chemotherapy-free combination therapy is specifically for patients with locally advanced or metastatic NSCLC who have epidermal growth factor receptor (EGFR) exon 19 deletions or exon 21 L858R substitution mutations, as detected by an FDA-approved test.

The FDA's decision was based on encouraging results from the MARIPOSA study, a late-stage clinical trial. In this study, the combination of Rybrevant, an EGFRxMET bispecific antibody, and Lazcluze, a third-generation EGFR tyrosine kinase inhibitor (TKI), demonstrated a 30% reduction in the risk of disease progression or death compared to AstraZeneca’s Tagrisso (osimertinib), another third-generation EGFR-TKI used in this patient population.

Additionally, the combination treatment increased the median duration of response by nine months compared to Tagrisso. The safety profile of the combination therapy was consistent with those of the individual treatments, suggesting no unexpected adverse effects from using the two drugs together.

NSCLC is the most common type of lung cancer, accounting for up to 85% of all cases. Among NSCLC patients, mutations in the EGFR gene are a frequent driver of the disease. Unfortunately, up to 39% of patients with EGFR-mutated NSCLC never receive second-line therapy due to disease progression and a lack of effective treatment options. This situation is complicated by acquired resistance mechanisms that develop following standard TKI monotherapy, making subsequent treatment more challenging.

Study investigator Alexander Spira of the Virginia Cancer Specialists Research Institute commented on the new approval, stating, “Patients will now have the option of a potential new first-line standard of care with significant clinical benefits over [Tagrisso].” He added that this new therapy aims to achieve the best possible patient outcomes while reserving chemotherapy for later stages of treatment when resistance becomes more complex.

This approval follows the FDA's earlier decision to authorize Rybrevant in combination with carboplatin and pemetrexed chemotherapy for the first-line treatment of locally advanced or metastatic NSCLC with EGFR exon 20 insertion mutations. Additionally, Rybrevant has received traditional approval to treat adults with locally advanced or metastatic NSCLC with EGFR exon 20 insertion mutations whose disease has progressed on or after platinum-based chemotherapy. This traditional approval updates the regulator’s May 2021 accelerated approval for the drug in this particular indication.

These advancements signify a significant step forward in the treatment of NSCLC, offering new hope for patients with specific genetic mutations that drive their cancer. The combination of Rybrevant and Lazcluze represents a promising new option for first-line treatment, potentially improving outcomes and extending the duration of response for many patients facing this challenging disease.