Strike 2: Roche flunks another phase 3 lung cancer test to leave TIGIT space reeling

Uh-oh. It was easy for Roche to brush off the failure of a high-risk bet on its anti-TIGIT drug tiragolumab in March. The indication was always a long shot. Now, though, tiragolumab has flunked a second phase 3 test, failing to improve on the progression-free survival (PFS) achieved by Tecentriq alone in patients with non-small cell lung cancer (NSCLC).

SKYSCRAPER-01 randomized 534 patients with first-line PD-L1-high locally advanced, unresectable or metastatic NSCLC to receive the checkpoint inhibitor Tecentriq in combination with either tiragolumab or placebo until disease progression, loss of clinical benefit or unacceptable toxicity.

The trial missed one of its co-primary endpoints, which looked at PFS. Data on the second co-primary endpoint, which is looking at overall survival, are immature. Roche is continuing the study until the next planned analysis in the hope that it fares better against the second co-primary endpoint.

“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,” Levi Garraway, M.D., Ph.D., chief medical officer and head of global product development at Roche, said in a May 11 statement. “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.”

Roche has readouts on the tiragolumab-Tecentriq combination in patients with cervical and esophageal cancers coming up, but the failure of the closely watched drug cocktail to move the needle in the first two trials may temper expectations. The setbacks also raise the specter of TIGIT becoming the latest target to emerge as an immuno-oncology darling only to ultimately fail to enhance checkpoint inhibitors.

If Roche’s failures reflect a targetwide problem, a clutch of leading biopharma companies will be caught in the fallout. Late last year, Gilead paid $725 million to license assets including Arcus Biosciences’ anti-TIGIT candidate domvanalimab, which continues to advance through interim analyses without the data being revealed, joining companies including Roche, Merck and GlaxoSmithKline in the space.