It’s now official: Johnson & Johnson’s combination of Rybrevant and Lazcluze has racked up an overall survival (OS) victory against AstraZeneca’s standard-of-care Tagrisso as a first-line treatment for advanced or metastatic non-small cell lung cancer (NSCLC).
In reporting positive top-line results from the phase 3 MARIPOSA study in 1,074 patients with NSCLC with EGFR exon 19 deletions or L858R substitution mutations, J&J’s combo is expected to keep patients alive for at least a year longer than Tagrisso.
The results, details of which are yet to be revealed, show a statistically significant and clinically meaningful improvement in OS, according to J&J.
While it was a secondary endpoint from the trial, OS is typically viewed by patients and physicians as the “gold standard endpoint,” according to Mark Wildgust, Ph.D., J&J’s vice president of oncology global medical affairs.
“The (result) really shows that we have a new standard of care for patients with EGFR non-small cell lung cancer,” Wildgust added in an interview with Fierce Pharma. “We know that Tagrisso gives about a three-year median overall survival. We’re expecting that we will be adding at least a year beyond that.”
As results from MARIPOSA have trickled out over the last several months, there has been increased anticipation that Rybrevant and Lazcluze could challenge Tagrisso’s dominance in the indication. AZ’s third-generation EGFR tyrosine kinase inhibitor has been on the market for nearly a decade and generated (PDF) sales of $5.8 billion in 2023.
Rybrevant and Lazcluze were approved by the FDA in the indication in August of last year. Days later, at the World Conference on Lung Cancer, J&J presented results that showed the combo reduced the risk of death by 23% versus Tagrisso. But victory couldn’t be declared until statistical significance was met.
J&J gained Lazcluze when it forged a partnership with South Korean biotech Yuhan Corporation in 2018. Three years later, Rybrevant gained its first FDA nod, to treat NSCLC patients with exon 20 insertion mutations.
Despite several failed attempts by AZ to pair Tagrisso with other immunotherapies, J&J saw Lazcluze’s potential as a combo agent because it “has a really pure cardiac safety profile and it also has a very good combinable profile in terms of interstitial lung disease,” Biljana Naumovic, J&J’s president, solid tumor, said in the interview.
The combo’s effectiveness comes from its dual mechanism—blocking the EGFR and mesenchymal-epithelial transition (MET) pathways.
“We showed that that dual targeting of EGFR and MET received less resistance coming through,” Wildgust said. The combo's survival benefit showed early, and “it was a question of just maturity of the data,” he added.
The advancement of the combo is positive news as the five-year survival rate is less than 20% for all people with advanced EGFR-mutated NSCLC. In the U.S., about 30,000 people are diagnosed annually with EGFR-mutated NSCLC, J&J said.
One of the values of the combo is that it can free treatment-naïve patients from using chemotherapy.
“Rybrevant and Lazcluze is the only option that can give life to patients and the only option that actually reserves chemotherapy in that second line, where chemotherapy belongs,” Naumovic said.
Naumovic's comment was a direct shot at AZ's Tagrisso-chemo regimen, which earned the FDA's blessing in February 2024.
Full data from the MARIPOSA trial will be presented later, J&J said, which will give the company a chance to talk about the study’s hyper-responders—those who achieve complete remission.
“We’re gonna be talking cure, for some patients. Who? We don’t know yet,” Naumovic said. “This is the hope that we are very confident that Lazcluze and Rybrevant are going to bring.”