JnJ chemotherapy free lung cancer treatment Rybrevant plus Lazcluze gets USFDA okay
New Jersey: Johnson & Johnson has announced that the U.S. Food and Drug Administration (FDA) has 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.
According to a recent release, 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. 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.
“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. 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. 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. Acquired resistance mechanisms after TKI monotherapy makes subsequent treatment more difficult.
“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. 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. “The 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.
