Asco 2023 – six months on Gilead/Arcus’s Tigit deflates

The run-up to this year’s Asco meeting saw a remarkable resurgence of interest in the Tigit mechanism, but today’s update on Gilead/Arcus’s Arc-7 study in NSCLC could puncture the enthusiasm. With 7.4 months’ additional median follow-up, and six more patients in each cohort, the PFS data for domvanalimab plus zimberelimab have deteriorated versus zimberelimab monotherapy. The anti-Tigit/PD-1 doublet that at December’s Asco virtual plenary had shown a 45% reduction in risk of progression or death, and a 6.6-month increase in median PFS versus the Arcus PD-1 alone, now stands at a 33% reduction and 3.9-month delta, today’s Asco update revealed. Not only that, but the confidence interval upper bound is now 1.13, having earlier stood precariously at 1.00 exactly. True, the shape of the PFS curves and small numbers of patients make it evident that just one or two early progressers might be making the difference. But the meaningfulness of Arc-7 was already in doubt, and the optics of a dataset that is clearly not improving will not go down well with fickle investors. Roche’s Morpheus-liver data, the cause of the recent run-up, will be presented in full at Asco tomorrow.

Gilead/Arcus's deteriorating Arc-7 dataset
  Tigit + PD-1 PD-1
Number enrolled 44 44
Date Dec 2022 (11.8mth median follow-up)
Median PFS 12.0mth 5.4mth
Stats for PFS HR=0.55 (0.31-1.00)
Number enrolled 50 50
Date Jun 2023 (18.5mth median follow-up)
Median PFS 9.3mth 5.4mth
Stats for PFS HR=0.67 (0.40-1.13)
Source: Asco.

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