With a phase 3 trial of Tecentriq in high-risk, muscle-invasive bladder cancer patients who had already had surgery, Roche was “hoping to show we could reduce the rate of progression to metastatic disease,” said Cathi Ahearn, vice president of global product strategy for Genentech’s oncology business unit.
But things didn’t work out that way.
The study, IMvigor010, missed its primary endpoint, with Tecentriq failing to outdo simple observation when it came to fending off cancer recurrence or death. The immuno-oncology drug cut the rate of those outcomes by just 11%, a figure that didn’t meet the statistical significance threshold.
The idea that Tecentriq might stall disease in the adjuvant setting—before patients’ cancer spread to other parts of the body—“made lots of sense scientifically, but this is the reason we do clinical studies,” Ahern said.
But when it comes to learning more about bladder cancer—and the differences between muscle-invasive urothelial carcinoma (MIUC) and metastatic urothelial carcinoma, where Tecentriq and many of its PD-1/PD-L1 peers are already approved—the trial was hardly a bust, she pointed out. On the contrary, just finishing a trial in that setting was, in itself, a victory.
Studies in adjuvant bladder cancer have been “notoriously difficult to do,” thanks to problems accruing patients, Ahern said. But because of IMvigor010, Roche now has information from the control arm—including the rate of cancer progression—that “gives us a lot more information about what the current state is for those patients.”
“The fact that we were actually able to complete the study puts us in a much better position than we were in even a year ago in terms of our understanding,” she added.
Roche also got some insight into how PD-L1 behaves in MIUC, where the study showed that patients’ lack of benefit wasn’t tied to levels of the biomarker in their tumors. Going forward, it can compare those insights to what it’s seen in the metastatic setting. The lessons the company can learn in the metastatic arena and translate into earlier disease—and those it can’t—is “one of the things we’re always eager to learn,” Ahern said.
Tecentriq, of course, has seen its fair share of ups and downs in the metastatic setting, too, with Ahern acknowledging that “it’s been something of a wild ride.” After becoming the first drug in its class into the disease area with a post-chemo nod in 2016, the following year, Tecentriq failed to show it could extend patients' lives. Another FDA nod—to treat those who weren’t eligible for initial chemo—was later limited to PD-L1-positive patients based on troubling trial findings.
Those are just a couple of the earliest examples of how much work still needs to be done “to learn how best to utilize” checkpoint inhibitors and “how to use them to the greatest effect for patients,” to hear Ahern tell it.
“We think that we’re in a strong position, with the volume of data we have and the quality of data we have—in terms of treatment effects and also in terms of underlying biology—to really dig into that and figure out what makes the most sense going forward,” she said. “I don’t have the answer today for what the best option’s going to be, but I think we’re well positioned to play an important role in answering that question.”