Just several days ago, BeiGene suffered a huge blow for its pipeline, in that its anti-TIGIT antibody ociperlimab (BGB-A1217), would not likely be able to achieve the primary endpoint of its phase 3 AdvanTIG-302 trial. The whole point of this study was to see if adding this drug with its approved PD-L1 inhibitor TEVIMBRA [tislelizumab] would be able to help treat adults with PD-L1 high, locally advanced or recurrent or untreated metastatic Non-small cell lung cancer. The PD-L1 high indicates that patients with high levels of this expression would have a higher chance of benefiting from treatment.
With that said, things definitely didn’t go as planned. An Independent Data Monitoring Committee, which reviewed findings of the pre-planned futility analysis, noted that it was highly unlikely that the primary goal of the study would be achieved. With this committee recommending trial termination, this is exactly what BeiGene chose to do, it terminated it.
It will be interesting to see the full data set to understand how well ociperlimab + TEVIMBRA did against KEYTRUDA [pembrolizumab]. Speaking of which, the company still wants to actually share such data at an upcoming medical meeting this year to learn and understand the science further behind an anti-TIGIT antibody.
There was and may even possibly be huge promise behind a TIGIT antibody, the problem is that it remains to be seen. What happens is that TIGIT, found on immune cells, binds to CD155 on cancer cells. This type of binding then causes the sending of inhibitory signals to T-cell receptors. In essence, this knocks out the ability for such T-cells (the immune system) to be able to attack and kill cancerous cells. It was believed that by inhibiting TIGIT, patients would have a better chance at fighting off their cancer.
Besides this being for BeiGene in that it was forced to scrap this phase 3 trial of ociperlimab in targeting these PD-L1 high NSCLC patients, it marked another huge setback for the anti-TIGIT class of drugs. Roche is another company who didn’t have a lot of luck with this class of drug. As a matter of fact, it reported back on November 25th of 2024 that the primary endpoint of overall survival for its phase 3 SKYSCRAPER-01 study, was not met. The goal of the study was to also target PD-L1 high previously untreated, locally advanced or metastatic NSCLC patients. However, this trial was set up to use anti-TIGIT antibody tiragolumab plus TECENTRIQ [atezolizumab] compared to that of TECENTRIQ alone.
Some hope on the horizon remains for the advancement of an anti-TIGIT molecule and this is with a small-cap biotech iTEOS Therapeutics and its partner GlaxoSmithKline. That’s because back on May 10th of 2024, it was revealed that anti-TIGIT Belrestotug + dostarlimab exceeded pre-defined efficacy criteria for clinically relevant activity. This was observed in an interim analysis, whereby tumor reduction was observed with every dose of Belrestotug combination versus that of monotherapy.
The company has hope that its anti-TIGIT will do what the others could not, which is to do better in terms of efficacy over monotherapies. Its confidence is likely boosted by the fact that it is enrolling in a phase 3 registrational study using Belrestotug + dostarlimab (GlaxoSmithKlines PD-L1 drug) to treat first-line advanced, unresectable, or metastatic PD-L1 high NSCLC patients.
Investors won’t have to wait long to see new data from the advancement of Belrestotug, because topline interim data from a phase 2 study using this combination to treat these specific NSCLC patients is expected in Q2 of 2025. Even better, both companies are also evaluating the use of Belrestotug + dostarlimab + an anti-CD96 antibody drug from GlaxoSmithKline [known as nelistotug]. It remains to be seen if these companies can reignite the anti-TIGIT drug class. However, the science is there if it is utilized properly. It will be important to keep an eye on this catalyst and others going forward as it relates to anti-TIGIT antibody drug development.
