Tagrisso (osimertinib), AstraZeneca’s targeted agent that dominates the global EGFR (epidermal growth factor receptor)-mutant NSCLC (non-small cell lung cancer) treatment market, could face a threatening challenge from a latecomer this year, a market surveyor said.

According to a recent report of Evaluate Vantage, the challenger is Leclaza (lazertinib) of Yuhan and its U.S. partner, Johnson and Johnson.

The report presented a predictable scenario on a one-on-one duel between Tagrisso and Leclaza in the stage-four EGFR-mutant NSCLC primary treatment market this year.

The market surveyor first noted the Mariposa study, the interim result of which will likely be unveiled this year. The study is a phase 3 clinical trial, which made a head-to-head comparison of Leclaza + Rybrevant (amivantamab) and Leclaza monotherapy with the Tagrisso monotherapy in the primary treatment of stage-four EGFR-mutant NSCLC.

According to its initial design, the Mariposa study will end in the first half of next year, but J&J has highlighted the possibility of an interim readout sometime this year.

“The trial gives J&J two shots at beating Tagrisso,” the report said.

This is because it is a cohort study that randomly allocated patients to two groups of Leclaza monotherapy and combination therapy with Rybrevant. And if one of the groups exceeds the Tagrisso monotherapy, it will change the standard treatment.

Notably, the combo therapy of Leclaza and Rybrevant can prevent the occurrence of resistance due to T790 mutation. It also has a broad treatment scope, including those with general EGFR mutation, new cMet abnormalities, and Exon 20 insert mutants resistant to EGFR-targeted agents.

"The risk, of course, is that combining multiple pharmacology in this way will result in unacceptable toxicity,” it said.

Nevertheless, Evaluate Advantage paid attention to AstraZeneca’s Flaura2 study, the result of which will likely come earlier than the Mariposa study.

Flaura2 tests front-line Tagrisso head-to-head against Tagrisso’s combination with one of two platinum-based chemotherapies – pemetrexed/carboplatin or pemetrexed/cisplatin. AZ pushes to draw results in the first half of this year and submit them to the regulator for actual application in the second half of this year.

The goal of Flaura2 is to show that combining Tagrisso with chemo can enhance efficacy, and Wolfe Research’s analyst Tim Anderson reckons that, based on the earlier NEJ009 and Opal studies, a PFS (progression-free survival) is likely,” said the report’s author, Jacob Plieth.

That means if Flaura2 proves the PFS benefits of Tagrisso + platinum chemo ahead of Mariposa, it can change the standard primary treatment. And if the standard treatment changes, it could make the result of Mariposa meaningless even if it ends with Leclaza’s victory because the latter is compared only with the Tagrisso monotherapy.

“However, the Mariposa study’s benefit scale is likely to remain bigger than that of Flaura2,” it said. “Accordingly, the Flaura2 may reduce part of Leclaza’s threats against Tagrisso, but not eliminate them.”

Investors and market analysts watch with great attention whether Leclaza, the frontrunner among Korean new drugs, can make a grand debut in global markets through a head-to-head fight with the original third-generation EGFR TKI (tyrosine kinase inhibitor).