ESMO 2025 preview – Roche comes clean on TIGIT

Roche isn't shying away from revealing the full extent of its misjudged foray into TIGIT blockade, planning to present the results of four more failed pivotal studies of tiragolumab at the upcoming ESMO conference.

These plans, revealed among the abstract titles ESMO has published so far, come a few months after AACR, where Roche unveiled data from Skyscraper-01, the lung cancer trial that had perhaps been tiragolumab's most important. The ESMO presentations will include a late-breaker on the liver cancer study Imbrave-152, which represented tiragolumab's last chance, but which was abandoned in July.

Imbrave-152 is the subject of one of two tiragolumab late-breakers, the other being Skyscraper-03, a study in first-line maintenance of stage III non-small cell lung cancer. Both of these were revealed in July to have failed for progression-free survival, and dealt the final blow for tiragolumab, whose development Roche terminated at the same time.

Lessons learned?

Given the discontinuation, interest in these trials will likely have more to do with lessons being learned – both about phase 3 decisions across drug development in general and about TIGIT in particular – and less with any future value of pursuing this target.

It will be intriguing to see, for instance, the margin by which a tiragolumab triplet in Imbrave-152 failed to beat Tecentriq and Avastin, given the apparent promise seen in the mid-stage Morpheus-liver trial at ASCO 2023. Also of interest will be tiragolumab's toxicity and overall survival data, which were said to have shown no trend towards a benefit.

At least Morpheus-liver did provide scientific backing for pursuing liver cancer in phase 3, which is more than can be said for most of the other indications in which Roche took tiragolumab into pivotal development.

These include oesophageal squamous cell cancer, where Skyscraper-07 was quietly revealed to have failed in April, and head and neck cancer, where the Skyscraper-09 trial was abandoned in January with nothing revealed about its results. Both studies will feature among regular oral presentations at ESMO.

Tiragolumab at ESMO 2025

Source: ESMO.

The key reason why Roche launched its massive pivotal TIGIT programme appears to have been the mid-stage Cityscape study in first-line PD-L1-expressing NSCLC. That result was shown to have been illusory when the phase 3 Skyscraper-01 trial in this setting yielded a non-significant 13% reduction in risk of death (p=0.22) at AACR.

Roche should be commended for not seeking to bury its TIGIT data but rather unveiling them for all to see at key medical congresses like ESMO. Earlier, at ASCO in 2022, it presented the results of its first key pivotal setback, the Skyscraper-02 study in first-line SCLC, which failed for PFS and OS despite most of its powering being assigned to the latter.

As for other prominent TIGIT blow-ups, neither Merck & Co's vibostolimab nor iTeos/GSK's belrestotug appear in the ESMO titles, at least on the information available so far. Searches also reveal nothing on Arcus/Gilead's domvanalimab, a project that looks increasingly risky.

One company still heavily invested in this mechanism is AstraZeneca with the anti-TIGIT x PD-1 bispecific rilvegostomig, whose phase 1/2 Artemide-01, and phase 2 Tropion-Pantumor03 (Datroway combo), studies will feature in ESMO's oral sessions.

ESMO will take place in Berlin on 17-21 October.