Roche's TIGIT flop prompts GSK, iTeos to reevaluate next steps for rival drug

That was fast. Just 39 hours after the bombshell failure of Roche’s TIGIT trial, iTeos Therapeutics revealed it and GlaxoSmithKline are assessing “how best to proceed with additional clinical development” of their rival asset in light of the phase 3 flop.

GSK paid iTeos $625 million upfront for the right to co-develop and co-commercialize anti-TIGIT antibody EOS-448 last summer. The agreement, which features up to $1.45 billion in milestones, positioned GSK to challenge Bristol Myers Squibb, Gilead, Merck and Roche for a sector that blossomed quickly in the wake of early evidence that hitting TIGIT enhances the effect of PD-1/L1 checkpoint inhibitors.

Merck and Roche rapidly expanded their clinical development programs in response to the data. Bristol Myers, Gilead and GSK bought their way into the sector. Now, the failure of Roche’s tiragolumab in a phase 3 non-small cell lung cancer (NSCLC) has caused companies to start reevaluating their strategies.  

“iTeos is working together with GSK to evaluate how best to proceed with additional clinical development of EOS-448 in light of the recent release regarding the Roche SKYSCRAPER-01 study,” iTeos wrote in a statement about its first-quarter results. 

The biotech added the comment to the bottom of a list of current and planned clinical trials of EOS-448. ITeos is continuing to study the TIGIT prospect in combination with GSK’s anti-PD-1 treatment Jemperli, Merck’s rival checkpoint inhibitor Keytruda and its own A2A receptor antagonist inupadenant in NSCLC and other solid tumors in phase 1/2 clinical trials. 

Enrollment in a multiple myeloma study that is testing EOS-448 as a monotherapy and in combination with Bristol Myers’ E3 ligase modulator iberdomide is continuing, too. And iTeos is still planning to start a pair of phase 1b trials of triplet combinations, one to test EOS-448 with Jemperli and inupadenant in patients with advanced solid tumors and another to assess the TIGIT prospect with Jemperli and GSK’s investigational anti-CD96 antibody in patients with NSCLC.

The studies show iTeos and GSK are continuing the multifront race to get EOS-448 to market while still taking the Roche flop seriously enough to consider how they proceed. The history of immuno-oncology drug development shows the TIGIT boom could unravel faster than it began if more clinical trials fail. In the spring of 2018, the failure of Incyte's IDO therapy triggered a rapid retreat from the once-hot target. 

Fierce Biotech has contacted iTeos for additional information.