NEW YORK – The US Food and Drug Administration on Tuesday approved Johnson & Johnson's anti-EGFR therapies Rybrevant (amivantamab) plus Lazcluze (lazertinib) as a first-line combination treatment for locally advanced or metastatic non-small cell lung cancer harboring EGFR exon 19 deletions or exon 21 L858R substitution mutations.
The agency approved the combination treatment after reviewing results from the Phase III MARIPOSA trial, which showed that Rybrevant-Lazcluze improved outcomes compared to single-agent treatment with AstraZeneca's EGFR inhibitor Tagrisso (osimertinib) in this setting. In the trial, among patients receiving Rybrevant-Lazcluze, median progression-free survival was 23.7 months compared to 16.6 months on Tagrisso. Median overall survival results were immature at the time of analysis, but researchers noted there was a trend favoring Rybrevant-Lazcluze over Tagrisso. The two-year survival rate at a median follow-up of 22 months was 74 percent on Rybrevant-Lazcluze versus 69 percent on Tagrisso.
This approval marks the first frontline combination regimen for EGFR-mutant NSCLC that does not include a chemotherapy agent.
"Patients will now have the option of a potential new first-line standard of care with significant clinical benefits over osimertinib," Alexander Spira, director of the Virginia Cancer Specialists Research Institute and a MARIPOSA study investigator, said in a statement. "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."
Rybrevant is also approved in combination with chemo as a first-line treatment for advanced NSCLC patients whose tumors harbor EGFR exon 20 insertion mutations. The EGFR-MET bispecific antibody is also approved as a monotherapy for second-line treatment of NSCLC with EGFR exon 20 mutations.
In 2018, Janssen Biotech acquired a license and began working with Yuhan Corp. to advance the EGFR tyrosine kinase inhibitor Lazcluze. The drug is sold in South Korea for treating EGFR T790M-mutated metastatic NSCLC under the brand name Laclaza.