Johnson & Johnson (NYSE: JNJ) announced today that the U.S. Food and Drug Administration (FDA) approved RYBREVANT^® (amivantamab-vmjw) plus LAZCLUZE™ (lazertinib) for the first-line treatment of adult patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) exon 19 deletions or exon 21 L858R substitution mutations, as detected by an FDA-approved test.^1,2

With this milestone, RYBREVANT^® plus LAZCLUZE™ becomes the first and only multitargeted, chemotherapy-free combination regimen with demonstrated superiority versus osimertinib approved for the first-line treatment of patients with EGFR-mutated NSCLC.^1,2 RYBREVANT^® is an EGFR- and MET^*-directed bispecific antibody that engages the immune system, and LAZCLUZE™ is a highly selective, brain-penetrant, third-generation oral EGFR TKI^**. RYBREVANT^® plus LAZCLUZE^™ is the only multitargeted regimen targeting both the common EGFR mutations directly.^1,2

"This approval is a crucial development for patients with EGFR-mutated NSCLC, who have faced significant unmet needs for far too long," said Jill Feldman^†, lung cancer survivor and co-founder of the EGFR Resisters, a patient advocacy group. "Having witnessed firsthand the remarkable evolution in lung cancer treatment, this profoundly important milestone brings a novel therapeutic approach to patients and their families. I'm thrilled that more patients can now experience the progression-free survival benefits seen in the MARIPOSA study."

Lung cancer is the leading cause of cancer mortality worldwide, resulting in 1.8 million deaths each year, with NSCLC accounting for 80 to 85 percent of all cases.^3,4 Of patients with EGFR-mutated NSCLC, between 25 and 39 percent never receive second-line therapy, due to disease progression and lack of treatment options.^5,6,7 The five-year survival rate is less than 20 percent for all people with advanced EGFR-mutated NSCLC treated with current standard of care TKI monotherapy.^8,9 Acquired resistance mechanisms after TKI monotherapy makes subsequent treatment more difficult.^8,9

"The unique combination of RYBREVANT and LAZCLUZE demonstrated superior efficacy in the first-line treatment of certain patients with EGFR-mutated advanced NSCLC as shown with the MARIPOSA study," said Alexander Spira^‡, M.D., Ph.D., FACP, Director, Virginia Cancer Specialists Research Institute, and study investigator. "Patients will now have the option of a potential new first-line standard of care with significant clinical benefits over osimertinib. This first-line therapy uses a targeted approach aiming to achieve the best possible patient outcomes while reserving chemotherapy for later stages of treatment when resistance becomes more complex."

The FDA approval is based on positive results from the Phase 3 MARIPOSA study, which showed RYBREVANT^® plus LAZCLUZE™ reduced the risk of disease progression or death by 30 percent compared to osimertinib (median progression-free survival [PFS]: 23.7 months versus 16.6 months) in the first-line treatment of patients with locally advanced or metastatic NSCLC with EGFR exon 19 deletions or exon 21 L858R substitution mutations.^1,2 The median duration of response (DOR) was nine months longer with RYBREVANT^® plus LAZCLUZE™ versus osimertinib (25.8 months versus 16.7 months), a secondary endpoint of the study.

"Building on more than three decades of oncology innovation, we are uniquely positioned to build best-in-class treatments where survival rates have remained stagnant for years," said Jennifer Taubert, Executive Vice President, Worldwide Chairman, Innovative Medicine, Johnson & Johnson. "RYBREVANT plus LAZCLUZE establishes a new benchmark in the advanced first-line setting, and we look forward to bringing this new chemotherapy-free treatment regimen to patients."

"Johnson & Johnson is deeply committed to setting new standards of care for people living with some of the most devastating and complex diseases of our time," said John Reed, M.D., Ph.D., Executive Vice President, Innovative Medicine, R&D, Johnson & Johnson. "Today's FDA approval of chemotherapy-free RYBREVANT plus LAZCLUZE in the first line is an incredible step towards our goal of altering the trajectory of lung cancer and reducing the impact of the world's leading cause of cancer mortality."

The safety profile of RYBREVANT^® plus LAZCLUZE™ was consistent with the profiles of the individual treatments. Venous thromboembolic events (VTE) were observed with the combination. Adverse event (AE) rates were consistent in this arm as compared to other RYBREVANT^® regimens.

MARIPOSA Publications & Presentations

Results from MARIPOSA were first presented at the European Society of Medical Oncology 2023 Congress and recently published in The New England Journal of Medicine. Results presented at the 2024 American Society of Clinical Oncology annual meeting and published in Annals of Oncology demonstrated the combination's significant benefit for patients who have at least one high-risk feature, which represents 85 percent of all EGFR-mutated NSCLC cases.¹⁰

Longer-term follow-up data from MARIPOSA will be presented at the International Association for the Study of Lung Cancer (IASLC) 2024 World Congress on Lung Cancer (WCLC) in September.

Regulatory Milestones

This approval marks the second new indication this year for RYBREVANT^®, following the March 1, 2024, U.S. FDA approval of RYBREVANT^® in combination with chemotherapy (carboplatin-pemetrexed) for the first-line treatment of patients with locally advanced or metastatic NSCLC with EGFR exon 20 insertion mutations, based on the Phase 3 PAPILLON study.¹

On June 17, Johnson & Johnson announced the submission of a Biologics License Application (BLA) to the U.S. FDA for a fixed combination of amivantamab and recombinant human hyaluronidase for subcutaneous administration (SC amivantamab) for all currently approved or submitted indications of intravenous (IV) RYBREVANT^®. This application is based on the Phase 3 PALOMA-3 study, with preliminary results showing a five-fold reduction in infusion-related reactions (IRR) with a five-minute administration of SC amivantamab.¹¹ Longer overall survival (OS), PFS and DOR were also observed with SC amivantamab.¹¹ On August 14, the U.S. FDA designated this application for Priority Review.