AstraZeneca may have recorded a double miss in a recent phase 3 study testing solo Imfinzi and an Imfinzi combo in newly diagnosed metastatic bladder cancer. But that doesn’t mean the results didn’t affirm the company’s broader strategy.
Neither the solo PD-L1 blocker nor Imfinzi in tandem with investigational CTLA4 drug tremelimumab significantly topped standard-of-care chemo at extending patients’ lives, according to data from the phase 3 Danube study presented Saturday at the European Society for Medical Oncology’s (ESMO's) virtual congress.
Imfinzi posted an 11% reduction in the risk of death among patients with high levels of biomarker PD-L1, helping people live a median 14.4 months compared with 12.1 months for chemo. The combo, meanwhile, slashed the death risk by 15% in the wider, all-comers study population, keeping patients alive for a median 15.1 months—three months longer than chemo did.
Neither of those results, though, met the bar for statistical significance.
Still, in a prespecified secondary analysis of the Imfinzi-tremelimumab combination, investigators did see “a suggestion that the combination is actually active” and driving some benefit for patients, said Dave Fredrickson, executive vice president and global head of AstraZeneca’s oncology business unit. And the effect was “further enhanced” in tumors with high PD-L1 expression levels.
That analysis “provides some confidence that the biomarker strategy we’re pursuing in the broader bladder program” is “probably right,” he added, pointing to Nile, a trial testing Imfinzi-chemo and Imfinzi-tremelimumab-chemo regimens against chemo; and Niagara, which is looking at Imfinzi with and without chemo in post-surgery patients.
These studies could also serve the dual purpose of helping AstraZeneca convert Imfinzi’s current, conditional bladder cancer approval in patients who have already had chemo into a full indication, Fredrickson noted. “We are still discussing with FDA how we will convert the bladder indication,” he said.
While five members of the PD-1/PD-L1 class bear approvals in late-stage bladder cancer, Imfinzi isn’t the only one of the bunch that’s struggled to rack up approvals for earlier use. Also Saturday at ESMO, Merck laid out details of a miss for its Keytruda-chemo combo in the same patient group.
That’s not to say Imfinzi didn’t shine in other areas, though. In stage 3 lung cancer—an area responsible for the “absolute preponderance of Imfinzi utilization,” as Fredrickson put it, pointing out that bladder cancer accounts for a single-digit percentage of the drug’s business—the immuno-oncology agent showed that at the four-year mark, it had kept 50% of patients alive, versus placebo’s 36.3%.
It’s “consistent and really encouraging to see that we’re having early interventions translate into durable patient benefit,” Fredrickson said.