Johnson & Johnson’s (J&J) combination therapy of Lazcluze (lazertinib) and Rybrevant (amivantamab-vmjw) has been granted marketing authorisation by the European Commission (EC) as a first-line treatment for patients with some types of non-small cell lung cancer (NSCLC).
The indication applies to advanced or metastatic cases involving epidermal growth factor receptor (EGFR) exon 19 deletions (ex19del) or exon 21 L858R (L858R) substitution mutations.
The approval is based on results from the Phase III MARIPOSA trial (NCT04487080), which compared the combination therapy to AstraZeneca’s Tagrisso (osimertinib), a widely used EGFR inhibitor. Data showed that the combination therapy reduced the risk of disease progression or death by 30% compared to Tagrisso monotherapy. Additionally, the median duration of response for patients receiving the combination therapy was nine months longer than for those treated with Tagrisso alone.
In addition to progression-free survival (PFS), which was the study’s primary endpoint, the combination also demonstrated improvements in secondary endpoints, including overall survival (OS). On 7 January 2025, J&J announced that the Phase III trial with Lazcluze and Rybrevant met its final pre-specified OS endpoint, delivering a statistically significant and clinically meaningful improvement in survival compared to Tagrisso.
Though not the primary endpoint, J&J described OS as the ‘gold standard endpoint’. J&J didn’t disclose specific data from the study, but the company said it expects its combination therapy to have improved median OS over Tagrisso by more than one year. In the Phase III FLAURA study (NCT02296125), AstraZeneca showed Tagrisso treatment led to a median OS of nearly 39 months.
Both Lazcluze and Rybrevant specifically target EGFR mutations that drive tumour growth in certain types of NSCLC. Tagrisso – which has been the standard of care in this setting – was approved by the EC last month for advanced NSCLC cases involving the same type of EGFR mutations. However, the new survival data from the MARIPOSA trial underscores the potential for Lazcluze and Rybrevant to challenge Tagrisso’s dominance in this treatment space.
Tagrisso achieved global sales of $5.8bn in 2023, as per AstraZeneca’s financials, reflecting its established position in the market. By comparison, GlobalData forecasts combined sales of $4.1bn for Lazcluze and Rybrevant by 2030. The recent approvals in both Europe and the US, where the combination was approved by the US Food and Drug Administration (FDA) in August 2024, are expected to further boost the adoption of the treatment.
GlobalData is the parent company of Pharmaceutical Technology.
