U.S. Approves RYBREVANT® + LAZCLUZE™ for First-Line Treatment of EGFR-Mutated Advanced Lung Cancer

Johnson & Johnson has announced the U.S. Food and Drug Administration (FDA) approval of RYBREVANT® (amivantamab-vmjw) combined with LAZCLUZE™ (lazertinib) for first-line treatment of adult patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) that features specific epidermal growth factor receptor (EGFR) mutations, namely exon 19 deletions or exon 21 L858R substitution mutations. This approval follows a Priority Review based on results from the Phase 3 MARIPOSA study, which demonstrated that RYBREVANT® plus LAZCLUZE™ reduced the risk of disease progression or death by 30% compared to osimertinib. Additionally, the combination showed a nine-month longer median duration of response.

This combination therapy marks a significant advancement as it is the first and only multitargeted, chemotherapy-free regimen indicated for this patient population, demonstrating better efficacy than osimertinib. RYBREVANT®, a bispecific antibody targeting EGFR and MET, engages the immune system, while LAZCLUZE™, a third-generation oral EGFR tyrosine kinase inhibitor (TKI), is known for its high selectivity and brain penetration. Together, they directly target the common EGFR mutations.

Lung cancer is the leading cause of cancer mortality globally, with NSCLC comprising 80-85% of cases. For patients with EGFR-mutated NSCLC, about 25-39% do not receive second-line therapy due to disease progression and limited treatment options. The current standard treatment's five-year survival rate for advanced EGFR-mutated NSCLC is below 20%. Resistance mechanisms acquired after TKI monotherapy complicate subsequent treatments.

The FDA's approval is grounded in the MARIPOSA study's findings, where RYBREVANT® and LAZCLUZE™ showcased a median progression-free survival (PFS) of 23.7 months, compared to 16.6 months for osimertinib. The median duration of response was 25.8 months versus 16.7 months for osimertinib, highlighting significant clinical benefits.

Dr. Alexander Spira, a study investigator, emphasized that this combination provides a new first-line standard of care with substantial clinical benefits over osimertinib. He noted that this targeted approach could improve patient outcomes and delay the need for chemotherapy to more advanced stages when resistance becomes more complex.

Johnson & Johnson's long-standing commitment to oncology innovation is reflected in this new approval, which is expected to set new benchmarks for the first-line treatment of advanced NSCLC. Jennifer Taubert, Executive Vice President, Worldwide Chairman, Innovative Medicine at Johnson & Johnson, expressed optimism about the potential of this new treatment regimen to improve survival rates.

The safety profile for the combination of RYBREVANT® and LAZCLUZE™ aligns with what is known about the individual treatments. Adverse events, including venous thromboembolic events, were consistent with previous observations in other RYBREVANT® regimens.

The MARIPOSA study, which included 1,074 patients, is a randomized Phase 3 trial evaluating the efficacy of the RYBREVANT® and LAZCLUZE™ combination against osimertinib and LAZCLUZE™ alone in patients with locally advanced or metastatic NSCLC harboring EGFR exon 19 deletions or exon 21 L858R substitution mutations. The primary endpoint was progression-free survival, with secondary endpoints including overall survival, overall response rate, duration of response, second progression-free survival, and intracranial progression-free survival.

RYBREVANT® is also approved in the U.S., Europe, and other markets globally for the treatment of NSCLC with EGFR exon 20 insertion mutations after progression on platinum-based chemotherapy. LAZCLUZE™, developed in collaboration with Yuhan Corporation, is a third-generation EGFR TKI targeting EGFR mutations while sparing wild-type EGFR.

With this FDA approval, Johnson & Johnson continues to push the boundaries in lung cancer treatment, offering new hope to patients and their families through innovative, targeted therapies.