Leclaza’s new trial data shows improved OS

Increases potential to become the first-line standard of care

Johnson & Johnson announces topline OS results from Phase III MARIPOSA trial

Expected to improve survival by more than 1 year over Tagrisso...over 50 months

Achieved with use of a targeted anticancer drug combination without chemotherapy…“Encouraging Results”

The Leclaza plus Rybrevant combination achieved statistically significant overall survival (OS) results.

 

Johnson & Johnson expects Leclaza plus Rybrevant to extend OS by more than a year compared to Tagrisso monotherapy.

 

The positive OS outcome for the combination strengthens its potential to become the first-line standard of care for EGFR-positive NSCLC.

 

On the 7th, Johnson & Johnson announced top-line OS results from the Phase III MARIPOSA study, which evaluated the efficacy of the combination of Leclaza plus Rybrevant in patients with locally advanced or metastatic NSCLC.

 

Leclaza is a third-generation tyrosine kinase inhibitor (TKI) targeting exon 19, and exon 21 (L858R) in EGFR-positive NSCLC that was developed by Yuhan Corp.

 

Johnson & Johnson acquired global rights to Leclaza and is conducting clinical trials for the drug in combination with its targeted therapy option, Rybrevant, which targets exon 20 and the MET mutation.

 

The recently published OS results showed that Leclaza plus Rybrevant was superior to Tagrisso monotherapy.

 

Johnson & Johnson explained that Leclaza plus Rybrevant extended median OS by more than a year compared to Tagrisso alone, which was a statistically significant result.

 

As Tagrisso achieved a median OS of 38.6 months in the FLAURA study that became the basis of its approval, the OS for Leclaza plus Rybrevant is expected to have exceeded 50 months.

 

This is progress over previous clinical data, which demonstrated efficacy in the primary endpoint of PFS, but only a favorable trend over Tagrisso in the secondary endpoint of OS.

 

OS is one of the most important indicators in determining the clinical value of an anticancer drug.

 

OS is the overall survival period from the time a patient starts treatment until death.

 

OS also includes patients who die of non-cancer-related causes, such as side effects and other complications.

 

In the case of PFS, PFS is the length of time that a patient survives with cancer that has not progressed, i.e., the tumor has not increased in size while receiving treatment.

 

In other words, while PFS is a measure of how well a new treatment can slow the progression of cancer, OS is a measure of how well it can prolong survival.

 

If the Leclaza plus Rybrevant is ultimately to have an effect in improving PFS and OS, it could become the standard of care for EGFR-positive non-small cell lung cancer.

 

Johnson & Johnson succeeded in receiving FDA approval for Leclaza plus Rybrevant in August of last year based on the results of the MARIPOSA trial.

 

In December last year, Johnson & Johnson received approval in Europe as well.

 

The approval was based on clinical results that Johnson & Johnson presented at the European Society for Medical Oncology 2023 Annual Congress (ESMO 2023).

 

The results showed a median progression-free survival (PFS) of 23.7 months in the Leclaza plus Rybrevant combination arm and 18.5 months in the Leclaza monotherapy arm, compared to 16.6 months in the Tagrisso monotherapy arm.

 

“Achieved results with targeted therapy+ targeted therapy”...ignites competition between combination therapies” The competition between combination therapies has also started in earnest in the market for the first-line treatment of EGFR-positive NSCLC.

 

Currently, AstraZeneca is defending the market with Tagrisso plus platinum-based chemotherapy, which is approved for the first-line treatment of EGFR-positive NSCLC.

 

However, platinum-based chemotherapy is categorized as an option for use after a patient develops resistance to conventional targeted therapies.

 

This is why some have argued that using platinum-based chemotherapy as a first-line option could lead to a shortage of later-line therapy options after developing resistance.

 

The downside to the use of the Leclaza plus Rybrevant combination is that it may be less convenient to administer.

 

All EGFR-positive targeted therapies, including Leclaza, Tagrisso (third generation), Boehringer Ingelheim’s Giotrif, Pfizer’s Vizimpro (second generation), Roche’s Tarceva, and AstraZeneca’s Iressa (first generation), are oral formulations.

 

However, Rybrevant is an intravenous (IV) formulation that requires clinic visits every three weeks.

 

This may not be convenient for patients with NSCLC.

 

To address the issue, Johnson & Johnson has developed a subcutaneous (SC) formulation of Rybrevant and has been studying the formulation in combination with Leclaza.

 

The subcutaneous formulation can be administered in as little as 10 minutes, significantly reducing dosing time for the patients.

 

In recently published clinical trial results, the combination of the subcutaneous formulation of Rybrevant and Leclaza demonstrated similar outcomes to the intravenous (IV) formulation of Rybrevant plus Leclaza.

 

Infusion-related adverse events were lower in the Rybrevant SC+ Leclaza arm.

 

“Leclaza+Rybrevant delivered clinically significant results without chemotherapy,” said Yusri Elsayed, Global Head of Oncology at Johnson & Johnson.

 

”Extending median overall survival by more than a year can be a game-changer in the NSCLC treatment landscape.”