No dato-dxd surprise in squamous lung cancer

Confirmation that Daiichi Sankyo/AstraZeneca’s datopotamab deruxtecan has no future in second-line NSCLC beyond the non-squamous histology has come courtesy of the Tropion-Lung01 study’s final overall survival analysis. The companies press released this yesterday, saying OS in all-comers, a co-primary endpoint, wasn’t statistically significant, but adding that final OS in patients with non-squamous NSCLC was “clinically meaningful”. Tropion-Lung01’s other primary endpoint, PFS in all-comers, was lacklustre but did hit statistical significance. However, confirmation that this benefit was driven by non-squamous disease came when the companies’ FDA submission for dato-dxd sought approval only in the non-squamous histology. The PDUFA date for the filing is assumed to be in December, and the extent of the subgroup OS benefit will be an important factor; this hasn’t been disclosed, but it’s possible that statistical significance isn’t being claimed here simply because of lack of powering after the all-comers OS fail. Also relevant here is dato-dxd’s anti-TROP2 ADC rival Trodelvy, from Gilead, which in the analogous Evoke-01 trial failed for OS, but was said to show an effect in patients non-responsive to last prior anti-PD-(L)1 therapy. The relevance of this subgroup benefit will be scrutinised on Friday when Evoke-01 data are presented as an ASCO late-breaker.

Summary of dato-dxd vs docetaxel in Tropion-Lung01

Notes: *subgroup representing the setting for a US approval filing; **co-primary endpoint. Source: OncologyPipeline & company statements.