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Before key Tagrisso showdown, J&J notches Rybrevant trial win in large lung cancer area

Johnson & Johnson’s Rybrevant is currently approved for a tiny non-small cell lung cancer (NSCLC) niche. A late-stage study could move the drug to a larger disease area where AstraZeneca’s blockbuster Tagrisso plays, but the most important readout still lies ahead.

Two regimens of Rybrevant combinations beat chemotherapy at preventing disease progression or death in patients with previously treated EGFR-mutant NSCLC, J&J said Wednesday.

The two experimental arms use Rybrevant and chemotherapy either with or without J&J’s Yuhan-partnered lazertinib. And both combos showed “statistically significant and clinically meaningful” improvements over chemotherapy in progression-free survival, J&J said.

The data mean that the phase 3 MARIPOSA-2 trial has hit its dual primary endpoint. Patients had EGFR exon 19 deletions or exon 21 L858R substitution NSCLC and had tried Tagrisso before enrolling in the study. Exon 19 and 21 changes are the two most common EGFR mutations, making up about 85% of all EGFR mutations, whereas exon 20—where Rybrevant is currently approved—only constitutes less than 10% of EGFR NSCLC cases.

Rybrevant’s commercial potential lies heavily in its ability to move into the exon 19 and 21 category. The J&J drug is a bispecific antibody targeting EGFR and MET. Lazertinib, a third-generation EGFR inhibitor, got its first approval in Korea in January 2021 to treat patients with EGFR T790M mutation-positive NSCLC following prior tyrosine kinase inhibitor treatment, the exact same indication as Tagrisso’s original FDA nod in 2015.

Although in a broader EGFR population, MARIPOSA-2 in the second-line setting is still a relatively small fish in J&J’s projected $5 billion peak sales pool for the Rybrevant-lazertinib regimen. The real focus for the company and experts watching the EGFR field is the readout from the MARIPOSA trial, expected later this year.

The high-stakes MARIPOSA study in the first-line setting is pitting the Rybrevant-lazertinib combo against Tagrisso, which generated $5.4 billion in 2022 sales. As Tagrisso is already established as the trusted first-line standard of care for EGFR-mutant NSCLC, J&J will likely require more than just evidence of disease progression improvement; it will need a compelling overall survival benefit to convince doctors.

In addition, Tagrisso monotherapy may no longer be the appropriate comparator as AstraZeneca recently touted a phase 3 success for the drug’s combination with chemotherapy. Details from that phase 3 study, coded FLAURA2, will be shared at the upcoming 2023 World Conference on Lung Cancer during the presidential symposium.