Roche's TIGIT ambitions take another blow

Roche's anti-TIGIT antibody tiragolumab has failed a second phase 3 trial, dousing expectations for the programme and its hopes of finding a companion to its cancer immunotherapy blockbuster Tecentriq.

When tiragolumab missed the mark in the SKYSCRAPER-02 trial in extensive stage small-cell lung cancer (ES-SCLC) in January, Roche said it was a challenging indication, and it was hoping for better results in the SKYSCRAPER-01 study in non-small cell lung cancer (NSCLC).

Those results are now in, and once again showed that adding the TIGIT drug to Tecentriq (atezolizumab) was unable to provide and improvement in progression-free survival (PFS) when used as a first-line treatment for people with PD-L1-high locally advanced or metastatic NSCLC.

The data on overall survival isn't mature yet, so Roche is continuing to follow patients to that endpoint, but that looks like a faint hope after the PFS miss even though Roche saw a non-significant trend towards better results with the combination on both measures.

While the ES-SCLC data could be shrugged off as a high-risk, speculative venture for tiragolumab, the NSCLC fail in Tecentriq's established territory is a heavier blow, and one investors fear could read through to the rest of the TIGIT programme, eroding away Roche's lead in the class. Shares in the Swiss pharma fell more than 4.5% this morning as the news emerged.

Roche is sticking with the drug, saying that ongoing trials in NSCLC and other cancers will continue as planned as it tries to show that two immunotherapies can be better than one, increasing the proportion of patients who respond to the treatment.

Like PD-L1, TIGIT is thought to act as a molecular brake that stops T cells from attacking tumours, and tiragolumab is currently leading the pack among drugs targeting the immune checkpoint.

TIGIT drugs from Merck & Co, Bristol-Myers Squibb/Agenus, Gilead/Arcus, GlaxoSmithKline/iTeos Therapeutics and Mereo Biopharma are in clinical trials already.

It remains to be seen if tiragolumab's troubles are an opportunity for its rivals – or an early indication that the mechanism itself is flawed as a cancer treatment.

"While these results are not what we hoped for in our first analysis, we look forward to seeing mature overall survival for this study to determine next steps," said the group's chief medical officer Levi Garraway in a statement on the top-line results.

"We continue to believe that TIGIT may have a role in cancer treatment and we will share additional results from our tiragolumab programme as they emerge."