'Leclaza·Rybrevant comb therapy' wins nod in KOR

following US·Euopean approvals

First-line treatment for patients with EGFR-positive NSCLC

Expected to improve OS over 1 year compared to Tagrisso

Yuhan

The approval of Leclaza plus Rybrevant combination therapy in South Korea has expanded treatment options for patients with non-small cell lung cancer (NSCLC).

 

As Leclaza combination therapy has shown a positive overall survival (OS) result, it is highly likely to be the first-line standard therapy for treating EGFR-positive NSCLC.

 

According to industry resources on January 13, the Ministry of Food and Drug Safety (MFDS) granted approval for Leclaza plus Rybrevant combination therapy as the first-line treatment for EGFR-positive NSCLC.

 

Following the approval, Leclaza plus Rybrevant combination therapy can be used in adult patients with advanced or metastatic NSCLC who have EGFR exon 19 deletion mutation or exon 21 (L858R) point mutation.

 

Following the approvals in the United States and Europe last year, Leclaza plus Rybrevant combination therapy was approved in South Korea as the first in Asia.

 

The US Johnson & Johnson aims to receive approval for Leclaza plus Rybrevant combination therapy in Japan and China.

 

The basis of approval is the MARIPOSA Phase 3 trial.

 

The study involved 1,074 patients with locally advanced or metastatic NSCLC.

 

The median age of patients was 63, and over half of the participants were Asian (59%).

 

Brain metastases occurred in 41% of the participants.

 

Patients were randomly assigned in a 2:2:1 ratio to Leclaza plus Rybrevant combination therapy, Tagrisso monotherapy, and Leclaza monotherapy.

 

The primary endpoint was progression-free survival (PFS), a period without disease progression, and the secondary primary endpoints were overall survival (OS), PFS after the first follow-up treatment (PFS2), and an overall response rate (ORR).

 

The clinical trial results showed the Leclaza plus Rybrevant combination therapy group had 23.7 months of PFS.

 

The Lecalza monotherapy group had 18.5 months of PFS, which was longer than the 16.6 months of the Tagrisso monotherapy group.

 

The Leclaza plus Rybrevant combination therapy group had 30% lower disease progression and death risk compared to the Tagrisso monotherapy group.

 

In the MARIPOSA study, adverse reactions of over Grade 3 were reported as 75% and 43% in the Leclaza plus Rybrevant combination therapy group and the Tagrisso monotherapy group, respectively.

 

Significant adverse reactions were reported at 49% and 33%.

 

Treatment-related adverse reactions in the Leclaza plus Rybrevant combination therapy group mainly were Grade 1-2, such as nail infection and rash.

 

Recently presented OS results showed that Leclaza plus Rybrevant combination therapy is superior to the Tagrisso monotherapy.

 

Johnson & Johnson explained that Leclaza plus Rybrevant combination therapy had statistically significant extended median OS over 1 year compared to Tagrisso therapy.

 

Since Tagrisso recorded an OS of 38.6 months in the FLAURA study, the basis of approval, the OS of Leclaza plus Rybrevant combination therapy will likely be around 50 months.

 

The current results indicate an improvement over previous clinical data.

 

Previously, the Leclaza plus Rybrevant combination therapy has demonstrated the efficacy regarding the primary endpoint, PFS.

 

The secondary endpoint, OS, had shown a favorable trend compared to Tagrisso.

 

If the efficacy of Leclaza plus Rybrevant combination therapy is confirmed in OS, in addition to PFS, then it will become the next standard therapy for EGFR-positive NSCLC.