[메디게이트뉴스 서민지 기자] The 31st Korean drug was born in 3 years following K-Cap.
On the 18th, Yuhan Corporation issued the Epidermal Growth Factor Receptor (EGFR) T790M mutation-positive non-small cell lung cancer treatment’Rexaza (English product name LECLAZA, ingredient name Lazertinib mesylate monohydrate)’ from the Ministry of Food and Drug Safety. Received item permission.
Based on the results of a phase 2 clinical trial (therapeutic exploratory clinical trial) conducted in Korea, Yuhan applied for permission under the condition to conduct a phase 3 clinical trial (therapeutic confirmation clinical trial) after marketing.
With the approval of the Ministry of Food and Drug Safety, it can be used to treat patients with EGFR T790M mutation-positive locally advanced or metastatic non-small cell lung cancer who have previously been treated with EGFR TKI.
Lexraza is an oral third-generation tyrosine kinase inhibitor (TKI) that has high selectivity for EGFR T790M-resistant mutations.It is generated by targeting wild-type EGFR due to its strong antitumor activity and low activity against wild-type EGFR. The likelihood of side effects is low.
It can pass through the blood-brain-barrier (BBB), showing excellent efficacy and excellent tolerability even in lung cancer patients with brain metastases.
Lung cancer is a fatal cancer with the highest mortality rate in Korea, and it is classified into small cell lung cancer and non-small cell lung cancer according to tissue type, and 85% of all lung cancers are non-small cell lung cancer. EGFR mutations are common in non-squamous cell lung cancer among non-small cell lung cancer and are diagnosed in about 30-40%.
According to domestic and international guidelines, it is recommended to administer 1st to 3rd generation EGFR TKI as the first line therapy for advanced or metastatic non-small cell lung cancer with positive EGFR mutations.
However, in most patients using the 1st and 2nd generation EGFR TKI, there is a limit that the disease inevitably progresses due to the acquisition of resistance in a large number of patients, and resistance due to the T790M mutation occurs in about 50-60% of the related resistances.
Recraza’s authorization is based on data derived from patients receiving Rexraza as a second-line treatment in a clinical trial of LASER201 (YH25448-201) in patients with advanced non-small cell lung cancer with positive EGFR mutations.
In the total dose group T790M mutation-positive patients (162 patients), the objective response rates according to independent median review and investigator evaluation were 59% and 68%, and the median progression free survival was 10.9 months and 11.0 months. Of the patients (78) assigned to the 240 mg dose group, the objective response rates according to independent central review and investigator evaluation of T790M mutation-positive patients (76) were 58% and 72%, and the median progression-free survival was 11.0 months and 13.2. It was months.
The intracranial objective response rate of patients with measurable brain metastases in all dose groups was 55% in the independent central review (22 patients), 64% in the investigator’s evaluation (22 patients), and intracranial in patients with assessable brain metastases. The median progression-free survival period has not yet been reached in both the independent central review (64 subjects) and the investigator evaluation (89 subjects) (median follow-up period of 10.9 months).
The intracranial objective response rate of patients with measurable brain metastases in the 240mg dose group was 71% in the independent central review (7 patients), 78% in the investigator’s evaluation (9 patients), and intracranial in patients with assessable brain metastases. The median progression-free survival was 16.4 months in the independent central review (24 subjects) and the investigator evaluation (40 subjects) has not yet reached the median value.
In terms of safety, only adverse reactions similar to general adverse reactions resulting from the use of 3rd generation EGFR-TKI were observed.
Most of the adverse reactions that occurred in the total dose group (181 patients) were grades 1 and 2 mild, and the most frequently reported adverse reactions were rash (29%), itchiness (28%), and constipation (22%). In 13% of patients, the dose was lowered due to an adverse reaction, and in 5%, the drug was discontinued due to an adverse reaction.
Interstitial pneumonia was reported in 1% (2) of patients, of which 1 was reported as a serious adverse reaction. The ECG QTc interval prolongation was found in 3% (6 patients) in the total dose group and 5% (4 patients) in the 240mg dose group, but all were mild, grade 1, and clinically significant decrease in left ventricular ejection rate (more than 10%). Decrease, and the absolute value is less than 50%) did not occur.
As a result, Rekraza was evaluated to show a significant therapeutic effect and safety profile as a second-line treatment for EGFR T790M mutation-positive non-small cell lung cancer.
Professor Ahn Myung-joo of the Department of Hematology and Oncology, Samsung Medical Center said, “Recraza is the first new drug developed in Korea to be published in the world-renowned journal, Lancet Oncology. “This approval will be a suitable treatment option for non-small cell lung cancer patients with positive EGFR T790M mutations.” Professor Ahn is the first author of the clinical thesis that was the background for this approval.
In addition, Professor Byeong-cheol Cho, director of the Lung Cancer Center at Yonsei Cancer Hospital, said, “The domestic approval of Rekraza has a lot of implications.” It is expected that it will be the hope of lung cancer patients around the world.” Professor Cho leads the licensed clinical trials of Rekraza and leads the study of multinational phase 3 clinical trials.
Lee Jung-hee, CEO of Yuhan Corporation, said, “Recraja is an innovative new drug created with Yuhan Corporation’s new drug development capabilities and the dedication of domestic researchers. It is a domestic new drug that has received hot interest and positive medical evaluation from the development stage.” “We are very pleased to be able to provide new treatment options for lung cancer patients in Korea.”
On the other hand, the clinical study of LASER201 (YH25448-201) has been conducted since January 2012 to evaluate the safety, tolerability, pharmacokinetics and anticancer activity of Rekraza.Parts A (dose escalation stage), B (dose expansion stage) , C (dose expansion stage: first-line treatment, second-line treatment cohort), and D (non-Korea countries).
Part A, B, and C 2nd line therapy subjects 181 and Part C 1st line therapy subjects 43 were conducted in Korea. Part D has a total of 29 enrolled in the United States, Spain and the United Kingdom, and is ongoing.