The U.S. Food and Drug Administration (FDA) has approved Johnson & Johnson’s Rybrevant (amivantamab-vmjw) for use in combination with standard chemotherapy (carboplatin and pemetrexed) to treat locally advanced or metastatic non-small cell lung cancer (NSCLC). This approval specifically targets patients with EGFR exon 19 deletions (ex19del) or L858R substitution mutations, whose disease has progressed after prior EGFR tyrosine kinase inhibitor treatment.
The FDA’s decision is based on results from the Phase 3 MARIPOSA-2 study, which demonstrated that Rybrevant, when used alongside chemotherapy, significantly reduced the risk of disease progression or death (progression-free survival [PFS]) by 52% compared to chemotherapy alone. This was the primary endpoint of the study. Notably, the median PFS for patients receiving Rybrevant plus chemotherapy was 6.3 months, compared to 4.2 months for those receiving chemotherapy alone. Additionally, the combination of Rybrevant and chemotherapy achieved a confirmed overall response rate (ORR) of 53%, in comparison to 29% with chemotherapy alone.
This latest approval marks the third new indication for Rybrevant this year. Earlier this year, the FDA granted approvals for Rybrevant in combination with Lazcluze (lazertinib) as a first-line treatment for patients with locally advanced or metastatic NSCLC with EGFR exon 19 deletions or L858R substitution mutations, based on the Phase 3 MARIPOSA study. The FDA also approved 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.
In June, Johnson & Johnson submitted an application to the FDA seeking marketing approval for a fixed combination of amivantamab and recombinant human hyaluronidase, intended for subcutaneous administration. This combination aims to provide an alternative to the intravenous (IV) administration of Rybrevant, currently used for all approved indications. The application is based on the Phase 3 PALOMA-3 study, where preliminary results showed a five-fold reduction in infusion-related reactions (IRR) with a five-minute subcutaneous administration of amivantamab.
This approval underscores the potential of Rybrevant as a valuable treatment option for patients with advanced NSCLC, particularly those with specific EGFR mutations. The development of subcutaneous administration could further improve patient experience and convenience.
