Trodelvy throws second-line lung cancer another curveball

Judging by Gilead’s 10% share price collapse the failure of the Evoke-01 trial of Trodelvy in second-line NSCLC spells yet more more disappointment for investors unhappy about the company’s $21bn acquisition of Immunomedics. But there is nuance in this hard-to-treat setting, where patients have progressed after platinum chemo and PD-(L)1 blockade. Notably, AstraZeneca/Daiichi Sankyo’s similarly acting anti-TROP2 antibody-drug conjugate datopotamab deruxtecan also underwhelmed in the Tropion-Lung01 trial; not only were those data pointedly not described as “clinically meaningful”, the PFS benefit versus docetaxel suggested utility only in NSCLC with non-squamous histology. Gilead played up a different, though also prespecified, subgroup analysis in Evoke-01, saying patients “non-responsive to last prior anti-PD-(L)1 therapy” saw a more than three-month mOS benefit. Not only that, but final OS analysis across the whole of Evoke-01 numerically favours Trodelvy; interim OS analysis from Tropion-Lung01 was numerically favourable but statistically insignificant. Gilead says patients in the ostensibly positive subgroup represent over 60% of Evoke-01’s population, and is taking the data to regulators. Around the time of ESMO Daiichi said it planned to file datopotamab on the back of Tropion-Lung01 by the end of 2023, but it’s unclear whether it has done so.

Cross-trial comparison of anti-TROP2 ADCs in 2nd-line NSCLC

Note: *PFS is a co-primary endpoint in Tropion-Lung01, and a secondary endpoint in Evoke-01. Source: ESMO 2023 & Gilead press release.