The targeted therapy lazertinib (brand name Lazcluze) has been approved by the Medicines and Healthcare products Regulatory Agency (MHRA) for treating eligible patients with non-small cell lung cancer (NSCLC).
This oral, third-generation, brain-penetrant epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) is indicated in combination with the bispecific antibody amivantamab (brand name Rybrevant) for the first-line treatment of adults with EGFR-mutated advanced NSCLC.
Lazertinib targets both the T790M mutation and activating EGFR mutations while sparing wild-type EGFR.
Clinical trial results have shown the amivantamab-lazertinib combination to have superior progression-free survival and overall survival compared to the current standard of care osimertinib.
The MHRA green light follows the approval of lazertinib by the European Commission in January 2025 for the same treatment combination and indication.
Efficacy of lazertinib in progression-free and overall survival
The MHRA approval was based on the results of the Phase 3 Mariposa study, which involved patients with previously untreated or osimertinib-pretreated EGFR–mutated advanced NSCLC.
A total of 1,074 patients underwent randomisation in a 2:2:1 ratio to receive amivantamab–lazertinib (open-label), osimertinib (blinded), or lazertinib (blinded, to assess the contribution of treatment components).
The primary endpoint was progression-free survival in the amivantamab–lazertinib group as compared with the osimertinib group.
The median progression-free survival was significantly longer in the amivantamab–lazertinib group than in the osimertinib group (23.7 vs 16.6 months; hazard ratio for disease progression or death, 0.70; 95% confidence interval [CI], 0.58 to 0.85; P<0.001).
Predominant adverse events were EGFR-related toxic effects. Discontinuation of all agents due to treatment-related adverse events was 10% with amivantamab–lazertinib and 3% with osimertinib.
The previous Phase 3 Laser301 study analysed the efficacy and safety of lazertinib.
In January, new positive topline overall survival (OS) results showed that amivantamab-lazertinib met the final pre-specified secondary endpoint of OS and demonstrated clinically meaningful and statistically significant improvement in OS versus osimertinib.
Improvement in median OS is expected to exceed one year, the researchers said.
This is therefore the first regimen to demonstrate superior OS benefit compared to the osimertinib current standard of care.
‘A significant step forward’
Speaking in January about the OS results of the Mariposa trial, Dr Antonio Passaro, medical oncologist of the Division of Thoracic Oncology, European Institute of Oncology in Milan, Italy, said of amivantamab-lazertinib: ‘This chemotherapy-free regimen has already demonstrated significant progression-free survival improvements, and new topline data suggests it is expected to extend life by a median of one year or more, in patients with untreated EGFR-mutated NSCLC versus the current standard of care, osimertinib.
‘These results mark a significant step forward in the treatment of EGFR-mutated NSCLC. Extending life expectancy is a critical indicator of a treatment’s impact. The Mariposa study reaffirms the potential of first-line treatment with this combination therapy to redefine the standard of care and offer clinically meaningful improvements in outcomes for patients.’
In December 2024, NICE published final draft guidance recommending durvalumab in combination with platinum-based chemotherapy as a neoadjuvant treatment before surgery, followed by durvalumab as adjuvant monotherapy after surgery for the treatment of adults with resectable NSCLC (tumours ≥4 cm and/or node-positive) and no known EGFR mutations or anaplastic lymphoma kinase rearrangements, for NHS use in England and Wales.
