Lazcluze (lazertinib)

For classical EGFR mutations such as exon 19 deletion and exon 21 L858R mutation, combination strategies in the first-line setting, based on the results of the MARIPOSA (lazertinib and amivantamab) and FLAURA 2 (platinum-based doublet chemotherapy and osimertinib) trials, provide promising outcomes. Optimising the treatment sequence in advanced EGFR-mutated NSCLC is crucial to ensure the best survival outcomes along with the best treatment tolerance and quality of life. Predictive biomarkers are strongly needed as well as biomarker-based escalation and de-escalation clinical trials.

In treatment-naive, EGFR-mutant oligometastatic NSCLC, adding upfront SBRT to lazertinib is a viable therapeutic option with a manageable safety profile.

P2, N=87, Active, not recruiting, Yonsei University | Not yet recruiting --> Active, not recruiting | Trial completion date: Dec 2025 --> Aug 2026 | Trial primary completion date: Dec 2024 --> Aug 2026

Thus, osimertinib remains an effective treatment with an excellent safety profile, perhaps to be considered as still the best option in the majority of elderly patients and in all patients that do not intend to trade-off an excess of toxicity with survival prolongment. The safety and efficacy characteristics of the three treatment options are the basis for a patient-tailored treatment choice, but in a significant proportion of patients, a personal and intimate approach to quality of life and survival prolongment is to be considered the main driver within a well-structured shared decision-making process.

P1, N=701, Active, not recruiting, Janssen Research & Development, LLC | Trial completion date: Jun 2026 --> Mar 2028

For metastatic disease, frontline combination strategies, such as osimertinib plus chemotherapy (FLAURA2) and amivantamab plus lazertinib (MARIPOSA), building on the EGFR-TKI backbone have improved progression-free and overall survival, particularly in higher-risk subgroups. Following progression on third-generation TKIs, potential avenues for overcoming resistance include mechanism-based strategies targeting MET amplification or EGFR C797S, as well as mechanism-agnostic approaches such as bispecific antibodies and antibody-drug conjugates (ADCs). Collectively, these recent advances reflect the dynamic nature of the therapeutic landscape for EGFR-mutant NSCLC, which is becoming increasingly individualized, mechanism-informed, and resistance-adaptive, in efforts to achieve durable systemic and intracranial disease control.

P2, N=43, Completed, Memorial Sloan Kettering Cancer Center | Active, not recruiting --> Completed | Trial completion date: Jul 2026 --> Dec 2025 | Trial primary completion date: Jul 2026 --> Dec 2025

P2, N=150, Active, not recruiting, Myung-Ju Ahn | Trial completion date: Jul 2025 --> Dec 2026 | Trial primary completion date: Mar 2025 --> Mar 2026