‘Leclaza can occupy 50% of mkt if used as combination'

Professor Byoung-Chul Cho, Professor Ki Hyeong Lee

Interim results of a Phase III trial that studies Leclaza’s use in combination with Rybrevant will be released in October

Key to competing with Tagrisso... “If the trial succeeds, Leclaza can succeed in the global market”

“Is another level from FLAURA 2 trial...raises expectations on the ‘targeted therapy+targeted therapy’ combo”

Yuhan Corp’s Leclaza (lazertinib) was the first homegrown new drug to be approved as a first-line treatment for EGFR mutation-positive non-small-cell lung cancer.

 

The industry’s eyes are now on how the drug will fare in the global market.

 

Will Leclaza be able to rise as a new contender to AstraZeneca’s ‘Tagrisso (osimertinib)’ that is dominating the global market?

 

The key lies in the clinical results of 'MARIPOSA', which is being conducted by Janssen.

 

The Phase III MARIPOSA study directly targets the current first-line standard-of-care Tagrisso with Janssen’s ‘Rybrevant (amivantamab)’ and Leclaza combination.

 

If the Rybrevant+Leclaza combination demonstrates a progression-free survival (PFS) superior to that of Tagrisso, this could bring major change to the current treatment environment.

 

The interim results of MARIPOSA phase 3 are expected to be presented at the European Society for Oncology (ESMO) Congress 2023 which will be held in October.

 

“If the MARIPOSA trial ends a success, third-generation options for the first-line treatment of EGFR-mutation-positive NSCLC will increase to 3 (Tagrisso, Rybrevant+Leclaza, Leclaza).

 

I think it's very significant that two-thirds of the options include the use of Leclaza."

Professor Byoung-Chul Cho (Medical Oncology, Yonsei Cancer Center) and Professor Ki Hyeong Lee (Hemato-Oncology, Chungbuk National University Hospital)

Professor Byoung-Chul Cho (Medical Oncology, Yonsei Cancer Center) and Professor Ki Hyeong Lee (Hemato-Oncology, Chungbuk National University Hospital) met with the reporter at the LASER Symposium that was held on the 22nd for medical oncologists and relayed their anticipation on Leclaza’s potential as a global new drug.

 

According to clinicaltrials.gov, a registry and results database of clinical studies, the MARIPOSA study divided 1,074 patients around the world into three treatment arms.

 

Treatment Arm A will receive Rybrevant+Leclaza and Arm B and C will each receive Tagrisso and Leclaza as monotherapy.

 

The study seeks to demonstrate that the Rybrevant+Leclaza combination therapy is superior to Tagrisso.

 

Tagrisso has settled as the global standard of care with progression-free survival (PFS) of 19 months when used in the first-line.

 

Therefore, achieving a statistically significant superiority will be very difficult.

 

Conversely, if the clinical trial produces good results, it would also be that much of a game-changer.

 

Professor Cho said, “The standard for statistical significance was set quite high in the clinical trial that compared Rybrevant+Leclaza and Tagrisso.

 

I have high expectations for the study because I believe the cancer treatment paradigm will shift from the use of monotherapy to combination therapies.

 

After the results of the MARIPOS clinical trial are presented, the company will sequentially start its approval process in the US.

 

If approved, two of the three options in the field will include the use of Leclaza, and simple arithmetic can tell us that the drug can occupy up to 70% of the market share.

 

"This will have a significant impact on prescriptions," he predicted.

 

Although it is not the main point of the trial, the study may also serve as an opportunity to recognize the effect of Leclaza once again as it also evaluates Leclaza and Tagrisso as monotherapy in one trial.

 

Leclaza demonstrated a long progression-free survival of 20.6 months in the global Phase III LASER301 trial that was presented last year.

 

Although this is longer than what Tagrisso had achieved in its Phase III trial, the two are not directly comparable due to the different patient groups enrolled in each study.

 

The MARIPOSA study includes Tagrisso and Leclaza monotherapy arms, which allows for the efficacy between the two to be examined.

 

Professor Lee said, “I want to know if the results from the LASER301 clinical trial and its subgroup analysis will show consistently in the MARIPOSA study.

 

If we see positive results in that trial, it would be an opportunity for HCPs to recognize the efficacy of Leclaza.

 

If successful, I believe Leclaza would be able to take over 50% of the market.” Tagrisso is also seeking to expand its indication through the FLAURA2 trial, which examined Tagrisso’s use in combination with chemotherapy.

 

The combination obtained statistically significant top-line results recently and will announce the results in the second half of the year.

 

However, the professors believe the FLAURA2 trial will not cause a major change in the current treatment landscape.

 

Professor Cho held the 1st generation gefitinib+chemotherapy combination in the past as an example.

 

The combination had shown a significant improvement in overall survival (OS), and a related paper was published in the Journal of Clinical Oncology (JCO) published by the American Society of Clinical Oncology (ASCO) and also listed in international guidelines.

 

However, no one has been actually prescribing this combination on-site.

 

Cho added, “Those who have experience dealing with a lot of EGFR mutations are confident that they can achieve the same results with monotherapy without adding chemotherapy.

 

Adding chemotherapy is effective with immunotherapy, but the situation is different in EGFR-mutation-positive NSCLC, as we are already achieving high response rates with targeted therapies alone.

 

The MARIPOSA trial is at another level compared with the FLAURA2 trial.” Professor Lee said, “Chemotherapy not only brings side effects, but I'm just personally not sure if it works.

 

I think chemotherapy will disappear from the market in the future.

 

With the advent of targeted therapy, there is no reason for us to go back and use chemotherapy, so it is difficult to understand why we should consider using it again even as a combination.”