Chemo-free regimen demonstrates efficacy in NSCLC

Janssen Pharmaceutical Companies of Johnson & Johnson’s Phase III MARIPOSA study is the first to show a clinically meaningful benefit in a chemotherapy-free regimen compared to the small molecule treatment TAGRISSO^® (osimertinib). This is based on positive topline results for Rybrevant^® (amivantamab-vmjw) in combination with lazertinib, as first-line anti-cancer treatment in locally advanced or metastatic EGFR-mutated non-small cell lung cancer (NSCLC).

The Phase III clinical trial demonstrated significant improvement in progression-free survival (PFS) in patients receiving Rybrevant with lazertinib compared to osimertinib.

Rybrevant and lazertinib

Rybrevant is a fully-human bispecific antibody targeting EGFR and MET with immune cell-directing activity.

Lazertinib is an oral EGFR TKI that targets both the T790M mutation and activating EGFR mutations while sparing wild type-EGFR, according to the company. An analysis of the efficacy and safety of lazertinib from the Phase III LASER301 study published in the Journal of Clinical Oncology in 2023, demonstrated lazertinib improved PFS compared to the first generation EGFR TKI gefitinib in all prespecified subgroups. In 2018, Janssen Biotech, Inc, entered into a license and collaboration agreement with Yuhan Corporation for the development of lazertinib, according to Janssen Pharmaceutical Companies of Johnson & Johnson.

The Phase III NSCLC trial

The MARIPOSA NSCLC study enrolled 1,074 patients and evaluated Rybrevant in combination with lazertinib versus osimertinib and versus lazertinib alone, in first-line treatment of patients with locally advanced or metastatic NSCLC with EGFR exon 19 deletions (ex19del) or substitution mutations. 

A planned interim overall survival (OS) analysis will determine the statistical and clinical significance of overall survival for these patients.

The Phase III data “underscore the potential for the Rybrevant and lazertinib regimen to advance treatment beyond TKI monotherapy,” commented Dr Alexander Spira, PhD, FACP, Director at the Virginia Cancer Specialists Research Institute, and study investigator.

“Positive topline results from the MARIPOSA study reinforce the potential of the Rybrevant and lazertinib combination in frontline EGFR-mutated non-small cell lung cancer as a future standard of care,” stated Dr Peter Lebowitz, PhD, Global Therapeutic Area Head for Oncology for Janssen Research & Development, LLC.