FDA approves RYBREVANT and LAZCLUZE for EGFR-mutated advanced lung cancer

The U.S. Food and Drug Administration (FDA) has approved the combination of RYBREVANT (amivantamab-vmjw) and LAZCLUZE (lazertinib) as a first-line therapy for adults with advanced non-small cell lung cancer (NSCLC) characterized by epidermal growth factor receptor (EGFR) mutations. This approval marks a significant advancement in the treatment landscape for patients with EGFR-mutated NSCLC, providing a much-needed chemotherapy-free regimen.

A Major Advancement in Lung Cancer Treatment

Johnson & Johnson’s latest approval is for the use of RYBREVANT, a bispecific antibody targeting both EGFR and MET, and LAZCLUZE, a third-generation oral EGFR tyrosine kinase inhibitor (TKI). This combination is now recognized as the first multitargeted regimen to offer a chemotherapy-free option with proven efficacy over osimertinib, the previous standard of care. RYBREVANT engages the immune system to target cancer cells, while LAZCLUZE is designed to penetrate the brain and address EGFR mutations that contribute to disease progression.

Jill Feldman, a prominent lung cancer survivor and co-founder of the EGFR Resisters, expressed her enthusiasm: “This pivotal approval represents a leap forward for patients with EGFR-mutated NSCLC. The new treatment regimen provides a novel and promising option that can significantly improve progression-free survival and overall patient outcomes.”

Addressing an Unmet Need in Lung Cancer Care

Lung cancer remains the leading cause of cancer mortality globally, responsible for approximately 1.8 million deaths annually. NSCLC accounts for 80 to 85 percent of all lung cancer cases. Despite advances in treatment, the prognosis for patients with advanced EGFR-mutated NSCLC has been dire, with a five-year survival rate of less than 20 percent using current standard TKI therapies. Many patients also experience disease progression and do not receive second-line therapy due to a lack of viable options.

The MARIPOSA study, a pivotal Phase 3 clinical trial, provided the evidence needed for this FDA approval. This study demonstrated that the combination of RYBREVANT and LAZCLUZE significantly reduced the risk of disease progression or death by 30 percent compared to osimertinib. With a median progression-free survival (PFS) of 23.7 months versus 16.6 months for osimertinib, and a median duration of response (DOR) 9 months longer, the new regimen offers a promising new treatment option.

Alexander Spira, M.D., Ph.D., FACP, Director at Virginia Cancer Specialists Research Institute and a lead investigator in the MARIPOSA study, highlighted the significance of these findings: “The efficacy of RYBREVANT and LAZCLUZE in the first-line treatment of EGFR-mutated advanced NSCLC establishes a new potential standard of care, offering substantial clinical benefits over osimertinib.”

New Treatment Paradigm and Future Outlook

The approval of RYBREVANT and LAZCLUZE sets a new benchmark for first-line treatment, potentially altering the treatment paradigm for EGFR-mutated lung cancer. By providing a multitargeted approach, this combination regimen addresses common EGFR mutations directly and may overcome some of the resistance mechanisms observed with traditional TKI monotherapies.

Jennifer Taubert, Executive Vice President at Johnson & Johnson, emphasized the company’s commitment to innovation: “Building on decades of oncology research, we are excited to introduce RYBREVANT and LAZCLUZE as a new standard in first-line treatment. This combination not only improves patient outcomes but also represents a significant step towards addressing the unmet needs in lung cancer care.”

John Reed, M.D., Ph.D., Executive Vice President of Innovative Medicine at Johnson & Johnson, added: “The FDA’s approval of RYBREVANT and LAZCLUZE is a milestone in our mission to transform cancer treatment and reduce the global impact of lung cancer.”

Safety Profile and Clinical Impact

The safety profile of RYBREVANT and LAZCLUZE is consistent with the known profiles of the individual drugs, though venous thromboembolic events (VTE) have been noted. Adverse event rates were comparable to those observed with other RYBREVANT regimens, reflecting the regimen’s overall safety.

The combination therapy represents a significant advancement in the management of EGFR-mutated NSCLC, potentially offering a more effective and patient-friendly treatment option. As the treatment landscape evolves, RYBREVANT and LAZCLUZE are poised to become a cornerstone of first-line therapy for advanced lung cancer.