TIGIT: Too Legit to Quit? Or Just Can't Hit?
Let's take a look at the controversial TIGIT landscape, what we know, and when we will know whether TIGIT is here to stay or not
The search for the next major checkpoint inhibitor to pair with PD-(L)1 inhibitors has led many to TIGIT, a promising but polarizing target. Despite early enthusiasm, data from Phase 2 and Phase 3 trials have been mixed at best, leaving the field unsure about TIGIT's true potential. While some players have exited the TIGIT race, others continue to hold out hope, awaiting critical readouts to determine whether TIGIT can still deliver a meaningful impact in immuno-oncology.
Below, I double-click into the latest developments in the TIGIT landscape, including both the setbacks and the ongoing trials that will shape the future of this target.
The TIGIT Phase 3 Graveyard
The first chart tells a story of high expectations that have met harsh realities. Several major Phase 3 trials for TIGIT-targeted therapies have been terminated or suspended. Some key takeaways:
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Novartis and BeiGene: Both companies pulled the plug on two major Phase 3 trials for ociperlimab (AdvanTIG-306 and AdvanTIG-301) in 1L NSCLC, seemingly for a “business decision”. These terminations were particularly significant given ociperlimab's early promise in combination with other therapies. The study entries note that the studies were not closed for safety reasons.
Merck: The KEYVIBE-010 and KEYVIBE-008 trials of vibostolimab + pembrolizumab were halted in both melanoma and SCLC, with the combination generating increased rates of immune-related and other AEs compared to the comparator arms of the studies. This was the first real signal I was able to find of TIGIT being terminated due to safety. All other terminations appeared to be due to lack of efficacy or inferential lack of efficacy given data from competitors in the space (aka a “business decision”).
Roche’s SKYSCRAPER Program: Roche terminated SKYSCRAPER-06 in NSCLC, adding to the growing doubts around tiragolumab. With another SKYSCRAPER trial suspended, it appears that even Roche—once one of the most bullish players in TIGIT—is grappling with significant challenges. Tiragolumab has somewhat become the poster child of “lack of efficacy” in the TIGIT space overall.
Gilead/Arcus’ ARC-10: The partners decided to end the study of their TIGIT + PD-1 combo in PD-L1 high patients to prioritize other TIGIT studies. The initial study regimen was being compared to market leader pembrolizumab, which has proven to be a high and difficult bar to surpass in this NSCLC segment. Reading the tea leaves, it would seem Gilead/Arcus didn’t feel confident in their TIGIT+PD-1 combo to pull ahead on efficacy and has instead pivoted to programs in combination with chemotherapy.
These terminations and suspensions reflect a troubling pattern for TIGIT-targeted therapies. While companies may have hoped that pairing TIGIT with PD-(L)1 inhibitors would replicate the success of PD-(L)1 + CTLA-4, the results so far have been underwhelming.