J&J’s Rybrevant in Combo with Lazertinib Clears Phase III in NSCLC

Johnson and Johnson

Pictured: J&J sign and office in Ontario/iStock, JHVEPhoto

Johnson & Johnson subsidiary Janssen announced Thursday that its bispecific antibody Rybrevant (amivantamab-vmjw) combined with lazertinib met the primary endpoint in the Phase III MARIPOSA trial, according to topline data from the study.

MARIPOSA is assessing the combination therapy as a first-line treatment for in patients with locally advanced or metastatic EGFR-mutated non-small cell lung cancer (NSCLC). Patients treated with the drug combo saw a statistically significant and clinically meaningful improvement in progression-free survival (PFS), as compared to those who received AstraZeneca’s Tagrisso (osimertinib).

Also, at the time the topline data were collected, overall survival (OS) showed a trend in favor of the Rybrevant regimen. The study will continue to follow patients until the next OS analysis for a more complete assessment of this endpoint, J&J said in Thursday’s announcement.

In terms of safety, the adverse events elicited by the combination therapy were consistent with what had been previously reported.

These initial data from MARIPOSA point to the potential of the Rybrevant-lazertinib combo regimen to become the “future standard of care” in EGFR-mutated NSCLC in setting, Peter Lebowitz, global therapeutic area head of oncology at Janssen, said in a statement.

J&J did not reveal specific data in its press release Thursday but promised to do so at an upcoming scientific congress.

Rybrevant is a bispecific antibody designed to target the EGFR and MET proteins. This dual affinity gives Rybrevant its three-pronged mechanism of action against cancer. The antibody blocks ligands from binding to EGFR and MET, thereby preventing uncontrolled cell division and proliferation. It also promotes the degradation of these receptors.

In addition, Rybrevant also tags the EGFR- and MET-bearing cancer cells for destruction by the immune system.

This approach to cancer works synergistically with lazertinib, an oral third-generation EGFR tyrosine kinase inhibitor (TKI) that specifically targets the T790M mutation and other similarly activating alterations on the EGFR gene, allowing it to bypass acquired resistance to earlier generation therapies.

“As a combination targeted regimen, Rybrevant and lazertinib inhibit critical oncogenic driver pathways and activate the immune system to address disease in multiple ways," Lebowitz said.

Earlier this month, J&J also released data from the Phase III MARIPOSA-2 study, demonstrating that Rybrevant—with or without Lazertinib—elicits significant and clinically meaningful PFS improvements in NSCLC patients who progress on or after Tagrisso treatment.

In July 2023, data from the Phase III PAPILLON study showed similar findings in which NSCLC patients treated with Rybrevant—in combination with chemotherapy—saw significantly better PFS versus chemotherapy alone.

PAPILLON is J&J’s confirmatory study for Rybrevant, which was granted accelerated approval in May 2021 for NSCLC with EGFR exon 20 insertion mutations.

Tristan Manalac is an independent science writer based in Metro Manila, Philippines. He can be reached at tristan@tristanmanalac.com or tristan.manalac@biospace.com.

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