Roche’s SKYSCRAPER-01 has fallen down. The phase 3 trial found adding the TIGIT candidate tiragolumab to Roche's approved checkpoint inhibitor had no effect on overall survival (OS) in non-small cell lung cancer (NSCLC).
Investigators enrolled 534 patients with PD-L1-high previously untreated, locally advanced unresectable or metastatic NSCLC. Participants were randomized to receive either tiragolumab or placebo in addition to Roche’s anti-PD-L1 drug Tecentriq. The TIGIT combination failed to improve progression-free survival in 2022 but interim data leaked in 2023 suggested an OS win was possible.
The positive trend seen in the interim analysis failed to translate into a statistically significant OS benefit in the final assessment. Roche broke the news in a brief statement Tuesday. Aside from revealing the missed primary endpoint, the drugmaker’s only update was that the overall safety profile was consistent with longer follow-up and no new safety signals were identified.
In a statement, Roche said it “continuously reviews its study programs to determine if any adjustments are necessary for the purposes of ongoing research” and “will apply the same principles to this program.” The drugmaker expects to generate more data from phase 3 studies across different settings or tumor types next year.
Other companies are targeting the same patient population as SKYSCRAPER-01 in other TIGIT trials. Arcus Biosciences and Gilead Sciences stopped a study in the setting at the start of the year, but BeiGene and Merck & Co. have fully enrolled trials with primary completion dates in 2026. GSK began enrollment in a phase 3 trial of its iTeos Therapeutics-partnered prospect in June.
The companies have pumped vast sums of money into licensing and developing anti-TIGIT antibodies in the belief they can counter a way tumors suppress immune responses. However, the results have so far failed to justify the outlay. Two tiragolumab combinations have now failed phase 3 NSCLC trials, and the drug candidate has also flunked a late-stage test in small cell lung cancer.
There remain opportunities to redeem TIGIT, in part because of the breadth of the bets placed by the top players. Roche alone began 10 phase 3 TIGIT trials between 2020 and 2024. In addition to lung cancer, Roche and its rivals have put their candidates up against tumors in the esophagus and liver.
Roche disclosed the latest TIGIT setback shortly before revealing it has struck a deal to buy Poseida Therapeutics for $1.5 billion. The takeover will give Roche control of a pipeline of off-the-shelf CAR-T cell therapies.