ESMO 2025 | SKYSCRAPER-07: atezolizumab with or without tiragolumab in patients with unresectable ESCC

TGIT is an immune checkpoint which is relevant in activated T cells, NK cells, as well as Treg. Tiragolumab is a human monoclonal antibody that targets against TIGIT and may have enhanced benefits when added to other immune checkpoint inhibitors such as atezolizumab. And in advanced esophageal squamous cell cancer there does seem to be incremental benefits. So with that background a large global Phase III trial was conducted at SKYSCRAPER-07. Patients who have completed definitive chemoradiation for esophageal squamous cell cancer were randomly allocated into three different groups. They will be followed by tiragolumab plus atezolizumab, atezolizumab on its own, or just placebo. And the primary endpoints in this study, however, is investigator-assessed progression-free survival and overall survival for the dual checkpoint inhibition tiragolumab plus atezolizumab versus placebo, but also the overall survival for the dual checkpoint inhibition, tiragolumab plus atezolizumab versus placebo, but also overall survival for atezolizumab alone versus placebo. As you will expect with a large study where 760 patients were randomized into these three groups, their baseline characteristics were well balanced. And what we observed is that the dual checkpoint inhibitions, in fact, did not result in any improvement in progression-free survival or overall survival. But when we look at the second treatment comparison of atezolizumab alone versus placebo, we observed an overall survival benefit with a hazard ratio of 0.69. So that’s a 31% relative reduction in the risk of death. And that translates into over 10% absolute overall survival benefits in favor of atezolizumab. We also observed an improvement in progression-free survival both by investigator-assessed as well as by independent radiological review board. So really the atezolizumab was showing a clinical meaningful benefit in overall survival and progression-free survival after completion of chemoradiation. In terms of safety we did not actually observe any additional safety concerns, although the dual tiragolumab plus atezolizumab did have a higher rate of side effects. So really, in conclusion, although the primary endpoint was not met in the SKYSCRAPER-07 of looking at the dual immune checkpoint inhibitions, the atezolizumab monotherapy for the first time in the last three decades have shown a clinically meaningful improvement in survival, overall survival and progression-free survival after definitive chemoradiation for esophageal squamous cell carcinoma.

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