Yuhan Corp....has received sales approval for Leclaza (Ingredient: Lazertinib), a drug targeting epidermal growth factor receptor (EGFR) T790M-mutated non-small-cell lung carcinoma (NSCLC), from the Ministry of Food and Drug Safety.

...E19Del, L858R alone or concurrent rare EGFR gene mutations (T790M, G719X, exon 20 insertion, S768I) 4....

...patients with NSCLC with local progressive or metastatic EGFR T790M mutation who have previously been treated with Generation 1 or Generation 2 EGFR TKI...

...Histologically confirmed, treatment naïve EGFR-mutant NSCLC, with or without T790M resistance mutation....

...G719X, S768I, L861Q, G719X + S768I, G719X + L861Q, L861Q + S768I, L747S, S720A, E709A, exon 18 deletion) without common EGFR mutations including exon 19 deletion, L858R, exon 20 insertion, or T790M....

...- Confirmed EGFR T790M mutation after the previous EGFR TKI...

...- Prior to enrolling in the study, patients must have central confirmation of T790M+ mutation status from a sample taken after documented progression on the EGFR-TKIs therapy according to cohort....

The objective response rate was 72.8%. The median progression-free survival (PFS) was not reached, and the PFS rates at 6 and 12 months were 81.7% and 65.1%, respectively....Our result demonstrates the real-world clinical efficacy of lazertinib in acquired EGFR T790M mutation.

This study included patients treated with lazertinib for T790M-mutated non-small cell lung cancer who had previously been treated with an EGFR-TKI….The ORR and DCR were 62.1% and 94.2%, respectively. The median follow-up duration was 11.1 months, and the median PFS period was 13.9 (95% confidence interval [CI], 11.0-not reached [NR]) months....The efficacy and safety of lazertinib was recapitulated in the real-world study reflecting routine clinical practice in Korea, showing a durable disease control both systematic and intracranially, with manageable side effects.

This study included patients treated with lazertinib for T790M-mutated non-small cell lung cancer who had previously been treated with an EGFR-TKI….The ORR and DCR were 62.1% and 94.2%, respectively...the median PFS period was 13.9 (95% confidence interval [CI], 11.0-not reached [NR]) months....In a subgroup of 33 patients with evaluable brain metastases, the intracranial DCR and ORR were 93.5% and 57.6%, respectively. The median intracranial PFS period was 17.1 (95% CI, 13.9-NR) months.

This integrated analysis of a phase 1/2 study (NCT03046992) assessed the efficacy and safety of lazertinib, a third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI), in patients with advanced EGFR T790M-positive non-small cell lung cancer (NSCLC) after prior EGFR TKI therapy....Among patients with T790M-positive tumors at baseline (n=76), 1 (1.3%) had a complete response and 41 (53.9%) had partial responses, giving an ORR of 55.3% (95% CI, 44.1-66.4). Median progression-free survival was 11.1 months (95% CI, 5.5-16.4).

CONTRADICTING EVIDENCE: The patients showed resistance to the treatment by acquiring the additional EGFR C797S mutation in cis which is also confirmed from the patient-derived cell lines.

...a total of 78 pts (49% female, median age 62) received at least one dose of lazertinib 240 mg….Of 78 pts, 76 pts with centrally confirmed T790M+ showed the objective response rate (ORR) 57.9% (95% CI 46.8, 69.0), the disease control rate (DCR) 89.5% (95% CI 82.6, 96.4), the median progression-free survival (PFS) 11.0 months (95% CI 5.6, 16.4) and the median duration of response (DoR) 13.8 months (95% CI 9.6, NR) by independent central review (ICR), respectively. Two pts (3%) experienced a confirmed complete response. The investigator-assessed ORR, DCR, median PFS and median DoR were 72.4% (95% CI 62.3, 82.4), 94.7% (95% CI 89.7, 99.8), 13.2 months (95% CI 9.6, not reached) and 11.8 months (95% CI 8.4, not reached), respectively....Lazertinib 240 mg has a favorable safety profile, and exhibits promising anti-tumor activity in pts with EGFR T790M+ NSCLC.

The ORR for 76 of the T790M-positive patients was 67% (95% CI, 55.4 to 77.5)...YH25448 was well tolerated and exhibits promising systemic and intracranial antitumor activity at multiple dose levels in EGFR T790M+ NSCLC patients.

Antitumor activity of YH25448 was investigated in vitro using mutant EGFR-expressing Ba/F3 cells and various lung cancer cell line....In various cell line models harboring EGFR activating and T790M mutation, YH25448 effectively inhibited EGFR downstream signaling pathways, leading to cellular apoptosis.