LASER301 (ClinicalTrials.gov identifier: NCT04248829) is a randomized, double-blind, multinational phase 3 study that evaluated the efficacy and safety of lazertinib among patients with EGFR-mutated (exon 19 deletion or L858R mutation) locally advanced or metastatic NSCLC who had not previously received any line of therapy for NSCLC....for patients with baseline CNS metastases in the LASER301 study, lazertinib significantly improved iPFS versus gefitinib, with more durable responses and a tolerable safety profile, suggesting that lazertinib has the potential to improve CNS outcomes in patients with EGFR-mutated NSCLC.

The phase 3 LASER301 study evaluated lazertinib efficacy and safety in treatment-naive patients with EGFR-mutated (exon 19 deletion or L858R) locally advanced or metastatic NSCLC....Between February 13, 2020, and July 29, 2022, among 258 patients of Asian descent, the median progression-free survival was significantly longer with lazertinib than gefitinib (20.6 versus 9.7 mo; hazard ratio: 0.46; 95% confidence interval [CI]: 0.34–0.63, p < 0.001), and the benefit was consistent across predefined subgroups (exon 19 deletion, L858R, baseline central nervous system metastases).

LASER301, a randomized, double-blind, multinational phase 3 study, evaluated efficacy and safety of lazertinib in treatment-naïve patients with EGFR-mutated (exon 19 deletion [Ex19del]/L858R) locally advanced or metastatic NSCLC….the median PFS was significantly longer with lazertinib than gefitinib (20.6 vs 9.7 months; HR, 0.46; 95% confidence interval [CI]: 0.34-0.63; P<0.001). PFS benefit of lazertinib versus gefitinib among Asian patients was consistent across predefined subgroups (Ex19del mutations: 20.8 vs 12.3 months; HR, 0.47; 95% CI: 0.31-0.71; P<0.001; L858R: 16.7 vs 9.6 months; HR, 0.44; 95% CI: 0.28-0.71; P=0.002; CNS metastases at study entry: 20.7 vs 9.5 months; HR, 0.33; 95% Cl: 0.18-0.58; P<0.001)....Lazertinib demonstrated better efficacy than gefitinib in Asian patients, with a tolerable safety profile.

This global, phase 3 study (LASER301) compared lazertinib versus gefitinib in treatment-naïve patients with EGFR-mutated (exon 19 deletion [ex19del]/L858R) locally advanced or metastatic non-small cell lung cancer (NSCLC)….Lazertinib demonstrated significant efficacy improvement compared with gefitinib in the first-line treatment of EGFR-mutated advanced NSCLC, with a manageable safety profile.

Patients with locally advanced or metastatic EGFRm NSCLC were randomised 1:1 to lazertinib (240 mg/day) or gefitinib (250 mg/day)….Median PFS was 20.8 months (95% confidence interval [CI]: 16.7-26.1) for lazertinib and 9.6 months (95% CI: 8.2-12.3) for gefitinib (hazard ratio [HR] 0.41, 95% CI: 0.28-0.60)....Significant PFS benefit with lazertinib was consistently observed across pre-defined subgroups, including patients with BM (HR 0.28, 95% CI: 0.15-0.53) and those with L858R mutations (HR 0.36, 95% CI: 0.20-0.63)....Consistent with results for the overall LASER301 population, this analysis showed significant PFS benefit with lazertinib versus gefitinib with comparable safety in Korean patients with untreated EGFRm NSCLC...

...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....

...Participant must have histologically or cytologically confirmed, locally advanced or metastatic, NSCLC, characterized at the time of locally advanced or metastatic disease diagnosis.Additional Cohort specific disease requirements include:Cohorts 1 and 3: EGFR Exon19del or L858R mutationCohort 2: EGFR Exon 20ins mutationEGFR Exon19del or Exon 21 L858R mutation (Cohort 1 and 3) or EGFR Exon 20 insertion mutation (Cohort 2) must have been identified as determined by an FDA-approved or other validated test of either ctDNA or tumor tissue in a CLIA certified laboratory (sites in the US) or an accredited local laboratory (sites outside of the US). ...

...- At least 1 of the 2 common EGFR mutations known to be associated with EGFR TKI sensitivity (Ex19del or L858R), either alone or in combination with other EGFR mutations...

...Presence of the sensitising EGFR-mutation (exon 19 deletion and/or L858R) detected by an accredited laboratory....

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

...Presence of the sensitising EGFR-mutation (exon 19 deletion and/or L858R) detected by an accredited laboratory....

...- Confirmed EGFR mutations (exon 19 deletion, L858R)(The result from both cell-free DNA or tissue-based DNA from the local test is allowed.)...

In 35 patients out of 43, common EGFR mutation of either Exon19Del (n=23) or L858R (n=12) was centrally confirmed. In this group, the confirmed ORR as per ICR was 77.1% (95% CI, 63.2 to 91.1), of which 6 patients (17.1%) had CR and 21 patients (60.0%) had PR. The DCR by ICR was 94.3% (95% CI, 86.6 to 100.0). The median DoR and PFS by ICR were 23.5 months (95% CI, 11.0 to NR) and 24.9 months (95% CI, 13.6 to NR) respectively....Lazertinib 240 mg demonstrated a median progression-free survival exceeding 2 years, promising and durable anti-tumor activity, including complete responses, and a favorable safety profile in this frontline cohort.