MADRID — The TIGIT class is on a wild roller coaster ride, dropping from mega heights, swerving around corners just barely hanging on and, at times, delivering thrills. And Roche is strapped into the first car for the long haul.
It’s paid off, says Charlie Fuchs, senior vice president and global head of oncology and hematology drug development at Genentech and Roche.
The Swiss pharma’s devout commitment was on display this summer when an inadvertent data disclosure from the SKYSCRAPER-01 trial in patients with first-line non-small cell lung cancer (NSCLC) showed that a combination featuring anti-TIGIT antibody tiragolumab led to median overall survival of 22.9 months, compared to 16.7 months in the Tecentriq monotherapy cohort. The hazard ratio was 0.81. Median follow-up at the time of the analysis was 15.5 months.
Fuchs acknowledges that the data are a bit immature, but he’s encouraged by the results nonetheless. He says Roche wants to see more events come in from that SKYSCRAPER-01 trial.
Last year, Roche revealed that adding tiragolumab to Tecentriq failed to improve progression-free survival (PFS) in an earlier cut of data from the phase 3 test. Fuchs isn’t sure PFS needs to be met for tiragolumab to be successful, given its other benefits.
“One thing that I think we’ve been upfront about is, with cancer immunotherapy, PFS is an important proxy. But there are examples in cancer immunotherapy where PFS is either modest or not really present as a benefit, but overall survival is positively influenced,” Fuchs said.
Roche has “heavily weighted” the trial towards overall survival rather than PFS, Fuchs explained.
“I would say that if you look at the data that got inadvertently disclosed on PFS, that magnitude of hazard ratio is pretty reasonable for what has been associated with approval of other drugs like PD-1 and LAG3 combinations,” he said. “So that was by intent, that we wanted to make sure that we had very mature survival data, and that we weighted our alpha heavily on overall survival and that was something we had done in the design of the study.”
The next readout for SKYSCRAPER-01 has moved from the fourth quarter of this year to the first quarter of 2024. Fuchs said that nothing should be read into that timing change, other than it’s an event-driven study.
As Roche has experienced its ups and downs, so too have its peers in the TIGIT space. Mixed data, endpoint failures and more have dogged the space.
But from Fuchs’ seat, he thinks the inadvertent disclosure of the SKYSCRAPER-01 data energized the field.
“This may be my skewed observation, that when we had the inadvertent data release earlier this year, it looked like some companies redoubled their efforts—and I won’t say who,” Fuchs said. “So I think if you look at the data from some of the other companies—and I won’t name them—it only further validates.”
TIGITs had a presence at ESMO but much of the data is in early days save for Roche’s own tiragolumab presentation. AstraZeneca touted phase 1/2 data the TIGIT drug rilvegostomig in NSCLC, although the readout was focused on safety rather than efficacy.
Novartis has backed off from TIGITs, ending a partnership with BeiGene for ociperlimab. The companies had been developing the candidate in a phase 3 NSCLC study as well as a phase 2 test in triple negative breast cancer. Like Roche, Gilead and Arcus have remained committed, presenting data in June that showed a reduced risk of disease progression in NSCLC.
Roche has a massive program for tiragolumab, with around 22 studies listed for the med on the company’s pipeline. Fuchs points to results from a phase 2 trial in first-line hepatocellular carcinoma that further prove his point. The therapy achieved a tripling of response rates and what he calls “a pretty meaningful improvement” in PFS.
“Now, it’s early data and the proof of the pudding will be in the phase 3. But I think you’re seeing enough signals from randomized phase 2 efforts both within Roche and other companies to say this target is likely to have a clinical benefit,” Fuchs said.
He continued: “There may be companies that have retreated. It seems to me that since our inadvertent data disclosure, they’ve looked at our data and said hey, you know what, we’re going to increase our investment.”