Janssen's Bispecific Antibody Rybrevant Achieves Dual Primary Endpoints in Phase 3 MARIPOSA-2 Trial, Demonstrating Significant PFS Improvement in EGFR-Mutated NSCLC Post-Osimertinib

▎WuXi

Edited by Kant Content Team

Today, Janssen, a subsidiary of Johnson & Johnson, announced,Its bispecific antibody therapy Rybrevant (amivantamab) achieved dual primary endpoints in the MARIPOSA-2 Phase 3 clinical trial.Compared with chemotherapy alone, the combination therapy of Rybrevant, chemotherapy with (or without) the oral tyrosine kinase inhibitor (TKI) lazertinib resulted in a statistically significant and clinically meaningful improvement in progression-free survival (PFS) for patients with locally advanced or metastatic non-small cell lung cancer (NSCLC). These NSCLC patients have tumors with EGFR exon 19 deletions (ex19del) or L858R mutations and experienced disease progression during or after treatment with the TKI osimertinib. Janssen plans to present detailed data, including secondary endpoints, at an upcoming scientific conference.According to the press release, MARIPOSA-2 is the first Phase 3 trial to show a statistically significant and clinically meaningful improvement in PFS for patients using osimertinib.

Worldwide, lung cancer is one of the most common cancers, with NSCLC accounting for 80% to 85% of all lung cancer cases. The most common mutation in NSCLC is in EGFR, a receptor tyrosine kinase that controls cell growth and division. Patients with advanced NSCLC who have EGFR mutations and are treated with EGFR tyrosine kinase inhibitors (EGFR-TKIs) have a five-year survival rate of less than 20%.

Rybrevant is a humanized EGFR/MET bispecific antibody.It has multiple mechanisms of anticancer action, not only blocking EGFR and MET-mediated signal transduction but also guiding immune cells to target tumors carrying activating and drug-resistant EGFR/MET mutations and amplifications. Rybrevant received accelerated approval from the U.S. FDA in May 2021 for the treatment of adult patients with locally advanced or metastatic NSCLC whose tumors have EGFR exon 20 insertion mutations as detected by an FDA-approved test and whose disease has progressed during or after platinum-based chemotherapy.

MARIPOSA-2 is an open-label, randomized Phase 3 trial evaluating the efficacy and safety of two regimens of Rybrevant (with and without lazertinib) and chemotherapy (carboplatin and pemetrexed). The study enrolled 657 patients with locally advanced or metastatic NSCLC harboring EGFR exon 19 deletion or L858R mutations who experienced disease progression during or after treatment with osimertinib.The dual primary endpoints of the trial were to compare PFS as assessed by blinded independent central review (BICR) in each experimental group versus chemotherapy alone.Secondary endpoints include objective response assessed by BICR, overall survival (OS), duration of response (DoR), progression-free survival after the first subsequent treatment (PFS2), and intracranial PFS, among others. All participants underwent continuous brain imaging to evaluate intracranial endpoints and assess the impact on the central nervous system (CNS) when Rybrevant is used alone or in combination with lazertinib.

Trial analysis showed that the trial met both primary endpoints, and no new safety signals were found when Rybrevant was added to chemotherapy.