642P - Phase II trial of lazertinib plus pemetrexed/carboplatin in patients with EGFR-mutant recurrent or metastatic non-small cell lung cancer who failed prior lazertinib (LUCAS): Interim analysis

Background

Despite the clinical benefits of third-generation (3G) EGFR-TKIs in non-small cell lung cancer (NSCLC), acquired resistance inevitably develops. Therefore, there is a need to explore effective treatment strategies beyond EGFR-TKI progression. This single-arm phase II trial, LUCAS, evaluated the efficacy and safety of continuing lazertinib (a 3G EGFR-TKI) while adding pemetrexed and carboplatin chemotherapy in patients (pts) with EGFR-mutant NSCLC who had failed prior lazertinib treatment.

Methods

Lazertinib 240 mg daily was combined with intravenous pemetrexed at 500 mg/m² and carboplatin with an AUC of 5, administered every 3 weeks. The primary endpoint is progression-free survival (PFS), with secondary endpoints including overall survival (OS), objective response rate (ORR), disease control rate (DCR), duration of response, intracranial PFS, and safety.

Results

Of the pre-planned 87 pts, 54 were enrolled by the data cut-off. The median age was 62, predominantly female (57.4%), and adenocarcinoma histology (98.2%). Regarding baseline EGFR mutation status, an exon 19 deletion was found in 32 pts, L858R in 20, and G719X and G719X+S768I in one each. Nine and 45 patients received lazertinib as 1^st line and 2^nd line treatments, respectively; 41.7% had baseline brain metastases. Among 54 pts, 48 were evaluable for response (EFR). Among the EFR subset with a median follow-up duration of 4.17 months, the median PFS was 6.18 months (95% CI 5.16 – 9.56). The median OS was not reached. The ORR and DCR were 31.3% and 91.7%, respectively. Among the safety analysis set, Adverse events (AEs) were reported in 94.4% of pts, with 64.8% experiencing grade 3 or higher. The most common AEs were thrombocytopenia (48.1%), anemia (46.3%), and neutropenia (40.7%), respectively. There was no treatment-related death.

Conclusions

In this study, we observed the clinical benefit of continuing lazertinib even after failure to lazertinib in EGFR-mutant NSCLC. The safety profile was tolerable, with manageable AEs. The trial is currently active, with an additional study aimed at exploring resistance mechanisms to previous lazertinib and its association with efficacy.

Clinical trial identification

NCT05786430.

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Yuhan.

Disclosure

M.H. Hong: Financial Interests, Personal, Advisory Board: AstraZeneca, BMS, Roche; Financial Interests, Personal, Invited Speaker: Merck, Yuhan, Janssen, Takeda, Amgen. H. Ahn: Financial Interests, Personal, Invited Speaker: Eisai, Boryung, Lilly Korea, LSK Korea, AstraZeneca Korea, Yuhan, Pfizer Korea, Novartis Korea, Sanofi/Aventis, MSD Korea, Boehringer Ingelheim, Celltrion, Daiichi Sankyo; Financial Interests, Personal, Advisory Board: Gilead, Amgen Korea, Roche Korea, Takeda, Daewoong, Bayer Korea. M. Ahn: Financial Interests, Personal, Advisory Board: AstraZeneca, Takeda, MSD, Yuhan, Amgen, Alpha Pharmaceutical, Janssen, Bristol Myers Squibb, Roche, Daiichi Sankyo, Merck, Boronoi. K.H. Lee: Financial Interests, Personal, Advisory Board: BMS, MSD, Eli Lilly, Yuhan, Pfizer, AstraZeneca; Financial Interests, Personal, Funding: Merck. All other authors have declared no conflicts of interest.