BeiGene bows out of TIGIT

BeiGene's Advantig-302 was the only remaining phase 3 trial of BeiGene's anti-TIGIT MAb ociperlimab not to have failed or been terminated – until today. Now the company has said that an interim analysis revealed futility for the overall survival primary endpoint, and not only is Advantig-302 being scrapped, but the entire ociperlimab programme has gone too.

Advantig-302 was comparing a combination of ociperlimab with Tevimbra against Keytruda in first-line lung cancer, an approach in which Roche's, Merck & Co's and Gilead/Arcus's rival TIGIT projects have all been abandoned. BeiGene's move leaves AstraZeneca's rilvegostomig and iTeos's GSK-partnered belrestotug as the only anti-TIGIT MAbs still ploughing this increasingly lonely furrow in phase 3.

GSK took a long time to start the phase 3 Galaxies Lung-301 trial, comparing belrestotug plus Jemperli against Keytruda, but finally did so last June after claiming that a similar phase 2 study had met efficacy criteria. And Astra's rilvegostomig is due to begin the Artemide-Lung04 study, in the same setting as Galaxies Lung-301 and Advantig-302, this month.

Astra is now the most heavily invested company in the TIGIT mechanism, running phase 3 trials of rilvegostomig across several NSCLC settings, as well as in gastric and biliary tract cancers. Notably, rilvegostomig is a bispecific MAb that combines TIGIT with PD-1 blockade, obviating the need to pair it with an approved anti-PD-(L)1 drug.

Litany of failures

However, the litany of failures is long. Roche's tiragolumab and Merck's vibostolimab once vied for the status of the most extensive pivotal TIGIT programme, but the former's hopes now basically hinge on liver cancer, while the latter was discontinued in its entirety in December.

Now BeiGene has added ociperlimab to this list of shame. Before the failure of Advantig-302 BeiGene had terminated the Advantig-301 study in stage III lung cancer, and withdrawn Advantig-306, which was to have tested an ociperlimab plus Tevimbra plus chemo triplet against Keytruda plus chemo in first-line NSCLC patients expressing PD-L1 down to 1%.

It's this latter setting on which Arcus/Gilead have doubled down with their anti-TIGIT MAb domvanalimab. Here the Star-121 trial is ongoing, testing domvanalimab plus zimberelimab and chemo; a focus on this trial as the way into first-line NSCLC followed the discontinuation of Arc-10, a zimberelimab combo trial with a design similar to BeiGene's now failed Advantig-302.

It's becoming increasingly hard to see that TIGIT blockade still has any role to play in first-line NSCLC. Skyscraper-01, Roche's tiragolumab trial whose blow-up presaged the coming setbacks, is to be presented at this month's AACR meeting, so perhaps this will reveal more about any remaining opportunity.

Pivotal studies of anti-TIGIT + PD-(L)1 combos in 1st-line NSCLC

Source: OncologyPipeline.