The top line results for the phase 3 clinical trial of the 3rd generation EGFR TKI ‘Lazertinib’ being developed by Yuhan Corporation have been announced. The results confirmed the efficacy of Lazertinib as a first-line treatment and Yuhan Corporation plans to submit an application for approval to expand indications in South Korea in Q1 of 2023.
This phase 3 clinical trial (LASER301) randomly assigned Lazertinib (240mg) and Gefitinib (250mg) among 393 patients with locally advanced or metastatic NSCLC (Non-Small Cell Lung Cancer) with EGFR mutation (Ex19Del or L858R) to compare efficacy and safety (NCT04248829). Patients who had refractory or relapse in the Gefitinib administration group were allowed crossover to receive open label Lazertinib. The study was conducted at 119 institutions in 13 countries, including South Korea.
In the Progression Free Survival (PFS) index set as the primary endpoint, Lazertinib was 20.6 months, whereas Gefitinib was 9.7 months. This statistically significant data results in Lazertinib reducing the risk of disease progression or death by 55% compared to Gefitinib (Hazard Ratio, HR 0.45, 95% Confidence Interval 0.34~0.58, p<0.001).
Subgroup analysis also confirmed the superiority of Lazertinib over Gefitinib in all subgroups. First, significant efficacy was confirmed in patients with the EGFR L858R mutation. In general, the L858R mutation is known to have poor prognosis against existing EGFR TKIs. However, the PFS of the Lazertinib-administered group was 17.8 months and the Gefitinib-administered group was 9.6 months (HR 0.41), confirming the excellent antitumor effect even in L858R patients. Second, efficacy was also confirmed in patients with brain metastasis. In the patient group with CNS metastasis, the PFS of the Lazertinib-administered group was 16.4 months and the Gefitinib-administered group was 9.5 months (HR 0.42), demonstrating excellent efficacy even in CNS metastasis patients with poor prognosis. Third, when Lazertinib was administered in the Asian subgroup, PFS was 20.6 months and Gefitinib was 9.7 months (HR 0.46), demonstrating excellent antitumor effect in Asians as well.
Interim analysis of the overall survival data, which is the secondary endpoint (data maturity 29%), showed a hazard ratio of 0.74 (95% CI 0.51~1.08, p=0.116), and the survival rate of patients who received Lazertinib at 18 months was 80% and Gefitinib was 72%.
Safety data showed that adverse events were mostly mild or moderate. Serious adverse effects of drug administration occurred at a level of 5% in Lazertinib and Gefitinib. The rate of drug discontinuation was 10% for Lazertinib and 9% for Gefitinib, with no significant difference between the groups.
Yuhan licensed out Lazertinib to Janssen Pharmaceuticals in 2018. Phase 3 clinical trial is ongoing in combination with Janssen’s EGFRxMET bispecific antibody ‘Amivantamab’ for NSCLC as 1st and 2nd line treatments. This phase 3 trial of Lazertinib monotherapy mentioned in the article is independent study by Yuhan as a new primary therapeutic option for patients with EGFR mutant-positive NSCLC.
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