Mariposa-2 might give J&J confidence in lazertinib

It won’t upstage AstraZeneca’s Flaura2 late-breaker at World Lung this weekend, but Johnson & Johnson’s apparent win in the Mariposa-2 trial just might be a vote of confidence in the group’s low-key, third-generation EGFR inhibitor lazertinib. But a major unknown is whether lazertinib adds anything on top of Rybrvant, J&J’s approved bispecific against EGFR and cMet. Mariposa-2 has been toplined positive for PFS, and so far suggests that EGFR-positive NSCLC patients who progress on Astra’s blockbuster Tagrisso might benefit from chemo plus Rybrevant with or without lazertinib versus chemo alone – with nothing said as to whether the triplet outperformed the Rybrevant/chemo doublet. The separate Mariposa trial remains the big test for the Rybrevant/lazertinib combo, having this year passed interim analysis without being halted for efficacy, and notably J&J has been playing down that study’s lazertinib monotherapy arm, in favour of the Rybrevant combo cohort. Astra is due to unveil data from the first-line Flaura2 study, combining Tagrisso with chemo and known to be positive for PFS, on Monday. Those data could determine whether, in using Tagrisso monotherapy as control, Mariposa is ultimately looking at the most relevant long-term comparator. Selected studies of targeted treatments for NSCLC Tagrisso (Astrazeneca)Rybrevant (J&J)Second lineTrialAura3ChrysalisSettingPost EGFRPost chemoEGFR statusT790mExon 20insAsset statusFully approvedAccelerated approvedSecond-line comboTrialSaffronSachiMariposa-2SettingPost TagrissoPost EGFRPost TagrissoDesignOrpathys combo, vs chemoOrpathys combo, vs chemoChemo combo +/- lazertinib, vs chemoEGFR statusExon 19del or exon 21 L858RNAExon 19del or exon 21 L858RcMet statuscMet+cMet+NAAsset statusData >2024Data 2024Toplined positive for PFS, Sep 2023First lineTrialFlauraFlaura2PapillonDesignMonotherapyChemo combo, vs monoRxMonotherapyEGFR statusExon 19del or exon 21 L858RExon 19del or exon 21 L858RExon 20insAsset statusFully approvedToplined positive for PFS, late-breaker at World Lung, 11 Sep 2023Poss confirmatory trial, toplined positive for PFS, Jul 2023First-line comboTrialSanovoMariposaDesignOrpathys combo, vs TagrissoLazertinib combo or lazertinib monoRx, vs TagrissoEGFR statusExon 19del or exon 21 L858RExon 19del or exon 21 L858RcMet statuscMet+NAAsset statusData 20242023 interim analysis passed without halt for efficacyMaintenanceTrialLauraNAEGFR statusExon 19del or exon 21 L858RAsset statusData H2 2023AdjuvantTrialAdauraAdaura2NAStageIB-IIIAIA2 or IA3EGFR statusExon 19del or exon 21 L858RExon 19del or exon 21 L858RAsset statusFully approvedData >2024NeoadjuvantTrialNeoadauraNAEGFR statusExon 19del or exon 21 L858RAsset statusData 2024Source: clinicaltrials.gov & company reports.