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 line | |||
Trial | |||
Setting | Post EGFR | Post chemo | |
EGFR status | T790m | Exon 20ins | |
Asset status | Fully approved | Accelerated approved | |
Second-line combo | |||
Trial | |||
Setting | Post Tagrisso | Post EGFR | Post Tagrisso |
Design | Orpathys combo, vs chemo | Orpathys combo, vs chemo | Chemo combo +/- lazertinib, vs chemo |
EGFR status | Exon 19del or exon 21 L858R | NA | Exon 19del or exon 21 L858R |
cMet status | cMet+ | cMet+ | NA |
Asset status | Data >2024 | Data 2024 | Toplined positive for PFS, Sep 2023 |
First line | |||
Trial | |||
Design | Monotherapy | Chemo combo, vs monoRx | Monotherapy |
EGFR status | Exon 19del or exon 21 L858R | Exon 19del or exon 21 L858R | Exon 20ins |
Asset status | Fully approved | Toplined positive for PFS, late-breaker at World Lung, 11 Sep 2023 | Poss confirmatory trial, toplined positive for PFS, Jul 2023 |
First-line combo | |||
Trial | |||
Design | Orpathys combo, vs Tagrisso | Lazertinib combo or lazertinib monoRx, vs Tagrisso | |
EGFR status | Exon 19del or exon 21 L858R | Exon 19del or exon 21 L858R | |
cMet status | cMet+ | NA | |
Asset status | Data 2024 | 2023 interim analysis passed without halt for efficacy | |
Maintenance | |||
Trial | NA | ||
EGFR status | Exon 19del or exon 21 L858R | ||
Asset status | Data H2 2023 | ||
Adjuvant | |||
Trial | NA | ||
Stage | IB-IIIA | IA2 or IA3 | |
EGFR status | Exon 19del or exon 21 L858R | Exon 19del or exon 21 L858R | |
Asset status | Fully approved | Data >2024 | |
Neoadjuvant | |||
Trial | NA | ||
EGFR status | Exon 19del or exon 21 L858R | ||
Asset status | Data 2024 |
Source: clinicaltrials.gov & company reports.
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