Asco 2023

Jun 23, 2023

After Arcus/Gilead's Tigit shocker yesterday, Asco today brought another bombshell. Roche's fact-finding mid-stage Morpheus-liver trial, which had sent Tigit-fixated investors’ pulses racing a week ago, has delivered a strong enough signal for a phase 3 trial to be launched, Asco learned this afternoon.

Presenting the Morpheus-liver data in full, UCLA's Dr Richard Finn outlined a global, placebo-controlled study, Imbrave-152/Skyscraper-14, that would pit tiragolumab, Tecentriq plus Avastin versus a Tecentriq/Avastin doublet in the front-line setting. This, he told Asco, would measure overall and investigator-assessed progression-free survival as co-primary endpoints, and was "expected to begin soon".

His enthusiasm was backed not only by the topline PFS numbers generated by Morpheus-liver, but also by a retrospective analysis using "Bayesian dynamic borrowing" designed to generate possible "synthetic" control arms. The purpose of this was to counter one of the readout's biggest criticisms, namely that Morpheus-liver's actual control arm vastly underperformed the performance of Tecentriq plus Avastin in Roche's Imbrave-150 trial, flattering the result.

The new analysis aimed to counteract imbalances in patients’ baseline criteria, and generated three possible more realistic controls, ranging from a conservative to a fully matched scenario. Each generated a positive reduction in risk of progression or death, from 28% to 51% with tiragolumab, Tecentriq plus Avastin, versus a Tecentriq/Avastin doublet. Meanwhile, Morpheus-liver showed a 58% reduction.

Still, it is not entirely clear why the mid-stage trial's actual control cohort underperformed. The Asco presentation revealed patients’ baseline imbalances, some of which favoured active treatment, though others, including disease severity, favoured control. Moreover, Morpheus-liver overall contained a lower percentage of hepatitis B patients than Imbrave-150.

All these considerations aside, Finn said the fundamental confounding issue might have been Morpheus-liver's relatively small size. The study discussant, Memorial Sloan Kettering's Dr Ghassan Abou-Alfa, said that while Bayesian modelling was intriguing Morpheus-liver should simply be celebrated for delivering a positive result that now needed corroborating in a larger trial.

Investors in other Tigit companies – not least Arcus – might be celebrating tomorrow, too.

This story has been updated to include more information about the "synthetic" control arms generated by Roche.