Johnson & Johnson’s RYBREVANT approved by FDA as second-line option for EGFR-mutated NSCL

The U.S. Food and Drug Administration (FDA) has approved Johnson & Johnson’s RYBREVANT (amivantamab-vmjw) in combination with chemotherapy for the treatment of adult patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) that features epidermal growth factor receptor (EGFR) exon 19 deletions or L858R substitution mutations. This approval targets patients whose disease has progressed following treatment with EGFR tyrosine kinase inhibitors (TKIs), such as osimertinib.

A vital second-line option for resistant cancer

This FDA approval marks a critical development in addressing the resistance mechanisms that frequently emerge in NSCLC patients treated with third-generation EGFR TKIs. RYBREVANT, combined with chemotherapy, aims to provide a crucial second-line treatment option, which significantly improves outcomes for those whose cancer has progressed.

In the Phase 3 MARIPOSA-2 trial, RYBREVANT in combination with standard chemotherapy (carboplatin and pemetrexed) demonstrated a 52% reduction in the risk of disease progression or death compared to chemotherapy alone. The study’s results showed a median progression-free survival (PFS) of 6.3 months for the combination therapy group, compared to just 4.2 months for patients receiving chemotherapy alone. Additionally, the overall response rate (ORR) was significantly higher in patients receiving RYBREVANT (53%) compared to those receiving only chemotherapy (29%).

Continuous advancements in 2024

This approval follows a series of significant regulatory developments for RYBREVANT in 2024. Earlier this year, the FDA approved RYBREVANT in combination with LAZCLUZE (lazertinib) for the first-line treatment of NSCLC patients with EGFR exon 19 deletions or L858R mutations. In March, RYBREVANT was approved for treating NSCLC patients with EGFR exon 20 insertion mutations.

Moreover, Johnson & Johnson is currently pursuing a subcutaneous formulation of RYBREVANT. This formulation aims to reduce infusion-related reactions, offer faster administration, and potentially enhance patient comfort during treatment. The FDA has designated this application for priority review, indicating the potential for rapid approval.

Key points:

• RYBREVANT approved for advanced NSCLC with EGFR exon 19 deletions or L858R substitution mutations.
• MARIPOSA-2 trial results showed a 52% reduction in disease progression risk with the combination of RYBREVANT and chemotherapy.
• The combination therapy extended progression-free survival to 6.3 months, compared to 4.2 months with chemotherapy alone.
• The drug continues to make strides with additional approvals and formulation advancements.

Expert insight

Oncologist Martin Dietrich emphasised that this multitargeted combination therapy helps address the common resistance mechanisms to existing EGFR TKIs. By extending progression-free survival and improving overall response rates, RYBREVANT-based regimens are set to offer more hope to patients facing treatment resistance.