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 Squamous NSCLCNon-squamous NSCLC*Final PFS4.4mth vs 3.7mthHR=0.75 (p=0.004)**2.8mth vs 3.9mthHR=1.385.6mth vs 3.7mthHR=0.63Interim OS12.4mth vs 11.0mthHR=0.90 (not stat sig)HR=1.32HR=0.77Final OS“Numerically favourable”, not stat sig**Presumed negative“Clinically meaningful”Notes: *subgroup representing the setting for a US approval filing; **co-primary endpoint. Source: OncologyPipeline & company statements.
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
| Squamous NSCLC | Non-squamous NSCLC* |
|---|
| Final PFS | 4.4mth vs 3.7mth
HR=0.75 (p=0.004)** |
2.8mth vs 3.9mth
HR=1.38 | 5.6mth vs 3.7mth
HR=0.63 |
| Interim OS | 12.4mth vs 11.0mth
HR=0.90 (not stat sig) |
| HR=1.32 | HR=0.77 |
| Final OS | “Numerically favourable”, not stat sig** |
| Presumed negative | “Clinically meaningful” |
