NSCLC standard treatment options undergo major change

Leclaza + Rybrevant combination listed as a NCCN Preferred therapy for first-line treatment

Tagrisso + chemotherapy combination is also Category 1…studies on combination therapies are actively pursued

Yuhan

The Leclaza + Rybrevant combination therapy has been recommended as the first-line treatment option by the National Comprehensive Cancer Network (NCCN) guidelines, based on its clinical utility.

 

With Tagrisso also listed as a preferred therapy in combination with platinum-based chemotherapy, combination therapy is expected to become the major strategy in first-line treatment for EGFR-positive non-small cell lung cancer (NSCLC).

 

According to industry sources on November 8, the NCCN recently revised its NSCLC treatment guidelines, including the combination of Yuhan's 'Leclaza (lazertinib)' and Janssen's 'Rybrevant (amivantamab)' as a Category 1 Preferred, first-line recommendation for EGFR-positive NSCLC.

 

Consequently, experts preferentially recommend combination therapy as first-line treatment when an EGFR exon 19 or exon 21 mutation is identified in NSCLC.

 

The Leclaza + Rybrevant combination therapy, which was first listed as a general recommendation last year, achieved the significant result of being changed to a Preferred recommendation in just about a year.

 

This opens the door to recognition of combination therapy as a Standard of Care (SOC) globally.

 

The NCCN provides guidelines for the diagnosis, treatment, and prognosis of cancer.

 

This organization is a federation of 32 institutions, including U.S.

 

National Cancer Centers and research institutes, and healthcare professionals worldwide refer to NCCN as a primary guide for cancer care and treatment.

 

The reason the Leclaza + Rybrevant combination therapy was listed as a Preferred recommendation by the NCCN is that it secured sufficient efficacy results.

 

Leclaza is a new EGFR-positive NSCLC drug developed by Yuhan, a 3rd-generation tyrosine kinase inhibitor (TKI) targeting exon 19 and exon 21 (L858R) mutations.

 

Johnson & Johnson secured the global rights to Leclaza and has been conducting clinical research to evaluate its efficacy in combination with Rybrevant, a targeted treatment option that targets exon 20 and the MET mutation.

 

The final overall survival (OS) analysis of the Leclaza + Rybrevant combination therapy showed superior OS compared to 'Tagrisso (osimertinib)' monotherapy.

 

This combination therapy is currently expected to secure the longest OS results among all pivotal clinical studies for EGFR-positive targeted therapies.

 

In the trial, the combination therapy group showed a statistically significant improvement in survival compared with the Tagrisso monotherapy group (p< 0.005).

 

In detail, the median OS for the Leclaza + Rybrevant group was not estimable (42.9 months-NE).

 

In contrast, the Tagrisso group showed an OS of 36.7 months.

 

Based on the distribution of survival indices, the Leclaza + Rybrevant group is expected to extend OS by at least 12 months compared with the Tagrisso group.

 

These study results were recently published in the New England Journal of Medicine (NEJM), attracting significant attention from the academic community.

 

Previously, Tagrisso monotherapy, a 3rd-generation TKI targeting EGFR exons 19 or 21, had been recommended as the Preferred treatment option in major guidelines, such as the NCCN guidelines.

 

However, the Leclaza + Rybrevant combination therapy, which is a 3rd-generation TKI similar to Tagrisso, demonstrated superior results compared to Tagrisso monotherapy, suggesting potential changes in key cancer treatment guidelines.

 

The Leclaza + Rybrevant combination therapy is achieving significant success in both the OS results, which were identified as the key to commercialization, and its NCCN guideline listing.

 

As the NCCN guidelines have been revised, the Leclaza + Rybrevant combination therapy has been recommended as the first-line treatment option.

 

Tagrisso + platinum-based chemotherapy receives the priority recommendation…combination with Rybrevant possible

AstraZeneca

Tagrisso was also recommended as a preferred therapy in combination with platinum-based chemotherapy, alongside its monotherapy use.

 

While Tagrisso became the SOC for first-line EGFR-positive NSCLC through monotherapy, the Leclaza + Rybrevant combination therapy joined the competition.

 

AstraZeneca received approval for Tagrisso in combination with platinum-based chemotherapy as a first-line EGFR-positive treatment.

 

The company aims to extend survival by using chemotherapy, previously a second-line treatment, at an earlier stage.

 

The Tagrisso + platinum-based chemotherapy combination therapy demonstrated efficacy compared with Tagrisso monotherapy in the FLAURA2 study.

 

The clinical results showed that the combination therapy recorded an OS of 47.5 months, longer than Tagrisso monotherapy's 37.6 months.

 

The median Progression-Free Survival (PFS) based on the investigators' assessment was 25.5 months, an extension of 8.8 months compared with Tagrisso monotherapy at 16.7 months.

 

AstraZeneca is confirming the possibility of combining its targeted therapies with various options.

 

The company is currently conducting combination trials of Tagrisso with the Antibody-Drug Conjugate (ADC) 'Datroway (datopotamab)' and the targeted therapy 'savolitinib'.

 

In addition, AstraZeneca is conducting a clinical trial in collaboration with the global Contract Research Organization (CRO) Parexel to assess the combination potential of Tagrisso and Rybrevant.

 

The Phase 2 OSTARA study began in July 2023 and is evaluating the efficacy and safety of the Tagrisso + Rybrevant combination therapy as a first-line treatment for EGFR-positive NSCLC.

 

With the efficacy of the Rybrevant + Leclaza combination therapy validated, AstraZeneca also plans to confirm the potential of combining Tagrisso with a targeted therapy.