ASCO: After lung cancer fails, Roche's faith in TIGIT rewarded as tiragolumab shows signs of life in liver cancer

On their most recent earnings call, Roche executives appeared to be giving coded messages about their strategy for anti-TIGIT checkpoint inhibitors. While they dodged questions about whether their candidate tiragolumab had flamed out of yet another phase 3 lung cancer trial, CEO Teresa Graham said the Big Pharma “continue to be really interested in the TIGIT pathway” and alluded to “several other data sets that will read out later this year as well.”

One of those data sets is likely to be from MORPHEUS, a wide-ranging series of phase 1b/2 trials assessing various cancer combo treatments. Specifically, one of these arms has been assessing tiragolumab with Tecentriq and Avastin in patients with unresectable, locally advanced or metastatic hepatocellular carcinoma (uHCC), and early data suggest that Roche’s continued faith in TIGITs may not be misplaced.

The results—published in an abstract ahead of the American Society of Clinical Oncology annual meeting—span 58 individuals with uHCC randomized to either receive the three-drug combination, or Tecentriq and Avastin alone, which is the current standard of care for the cancer.

In contrast to the high-profile lung cancer fails last year, when it came to this liver cancer study the objective response rate was significantly higher (42.5%) in the tiragolumab arm than for the standard of care arm (11.1%). At 11.1 months, median progression-free survival was also longer for the tiragolumab arm than the 4.2 months recorded for patients receiving Tecentriq and Avastin alone.

Overall, grade 3/4 adverse events related to treatment were similar between the two cohorts, at 27.5% and 33.3%, respectively, with events leading to discontinuations at 22.5% and 22.2%.

Roche concluded that adding its TIGIT candidate to the established Tecentriq-Avastin combination “resulted in higher ORR and longer PFS … and no new safety signals were identified.”

“These data suggest that [tiragolumab with Tecentriq and Avastin] may be a promising novel first-line treatment option for patients with uHCC, and support further study in this setting,” the Big Pharma added.

The results will provide some welcome goods news to Roche and other companies still pursuing the TIGIT route despite some clinical setbacks. Roche’s SKYSCRAPER trials last year were unable to demonstrate that tiragolumab could match the progression-free survival achieved by Tecentriq alone in patients with non-small cell lung cancer. More recently, Merck & Co. has also struggled.

One of Roche's failed lung cancer trials, SKYCRAPER-01, is due to produce a final analysis in the third quarter. Even if those results confirm that the study was a dud, eyes will remain on Gilead and Arcus, who have already teased phase 2 data suggesting their own TIGIT domvanalimab may have more luck in non-small cell lung cancer.