U.S. Approves RYBREVANT® Combo for EGFR-Mutated Advanced Lung Cancer

Johnson & Johnson has announced that the U.S. Food and Drug Administration (FDA) has approved RYBREVANT® (amivantamab-vmjw) in combination with standard chemotherapy (carboplatin and pemetrexed) for treating adult patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) characterized by epidermal growth factor receptor (EGFR) exon 19 deletions (ex19del) or L858R substitution mutations after progression on EGFR tyrosine kinase inhibitors (TKIs).

The approval is supported by the Phase 3 MARIPOSA-2 study, which demonstrated significant improvements in progression-free survival (PFS) and overall response rates (ORR) with the combination of RYBREVANT and chemotherapy compared to chemotherapy alone. The study showed a 52% reduction in the risk of disease progression or death, with a median PFS of 6.3 months for the combination therapy, compared to 4.2 months for chemotherapy alone. Additionally, the ORR for the combination treatment was 53%, compared to 29% for chemotherapy alone.

Experts in the field, such as Dr. Martin Dietrich from the Cancer Care Centers of Brevard, and Andrea Ferris, President and CEO of the LUNGevity Foundation, have expressed optimism about the new treatment option. Dr. Dietrich highlighted that the combination could address common resistance mechanisms to third-generation EGFR TKIs like osimertinib. Ferris emphasized the importance of new therapies in improving outcomes for patients with EGFR-mutated lung cancer.

The safety profile of RYBREVANT in combination with chemotherapy was consistent with the known profiles of the individual treatments. Permanent discontinuation due to adverse reactions occurred in 11% of patients. Common adverse events included infusion-related reactions, rash, and fatigue.

This approval marks the third new indication for RYBREVANT within the year, following its approval for first-line treatment of advanced NSCLC with specific EGFR mutations and for first-line treatment in combination with LAZCLUZE™ (lazertinib). Johnson & Johnson also recently submitted a Biologics License Application for a subcutaneous formulation of RYBREVANT, which has shown promising preliminary results in reducing infusion-related reactions and improving overall survival metrics.

RYBREVANT is a bispecific antibody targeting EGFR and MET receptors, aiding in immune cell-directed activity. It is approved in several regions, including the U.S. and Europe, for treating NSCLC with EGFR exon 20 insertion mutations after progression on platinum-based chemotherapy.

The MARIPOSA-2 study enrolled 657 patients with advanced NSCLC who had progressed on or after osimertinib treatment. The study compared the efficacy and safety of RYBREVANT plus chemotherapy to chemotherapy alone. Secondary outcomes included overall survival, duration of response, and time to subsequent therapy.

RYBREVANT has various ongoing clinical trials, including the MARIPOSA study assessing its combination with LAZCLUZE versus osimertinib, and the PAPILLON study evaluating its use with chemotherapy in first-line treatment of NSCLC with EGFR exon 20 insertion mutations. Additionally, the PALOMA-3 study is investigating the subcutaneous formulation of RYBREVANT.

Lung cancer remains a leading cause of cancer-related deaths globally, with NSCLC accounting for the majority of cases. EGFR mutations are prevalent in a significant portion of NSCLC patients, particularly among Asian populations. The five-year survival rate for advanced NSCLC with EGFR mutations remains low, underscoring the need for effective treatments like RYBREVANT.

With these advancements, Johnson & Johnson continues to solidify RYBREVANT's role as a crucial treatment option for patients with EGFR-mutated NSCLC, providing new hope and improved outcomes for those affected by this challenging disease.