The immune checkpoint inhibitor Tecentriq (atezolizumab) failed to improve overall survival in a subset of patients with locally advanced or metastatic urothelial cancer (mUC). The findings mean that Genentech‘s Phase 3 trial — which measured the drug’s efficacy in patients whose disease progressed on or following platinum-based chemotherapy — did not meet its primary endpoint.
“While these results are not what we had expected, we believe that Tecentriq will continue to play an important role in the treatment of people with advanced bladder cancer,” Sandra Horning, MD, chief medical officer and head of Global Product Development, said in a news release. “We are committed to helping people with advanced bladder cancer and will discuss these data with health authorities.”
Tecentriq, a programmed death-ligand 1 (PD-L1) inhibitor, was granted accelerated approval in the U.S. in May 2016 for patients with locally advanced or metastatic urothelial carcinoma (mUC) whose disease progressed during or following platinum-based chemotherapy. It marked the first time the U.S. Food and Drug Administration had approved an anti-PD-L1 cancer immunotherapy, and the first time in three decades that a treatment for a specific type of bladder cancer had been approved.
The approval was based on early evidence from the IMvigor210 Phase 2 (NCT02108652) trial, an open-label, multicenter, two-cohort study that treated 310 patients with Tecentriq every three weeks until disease progression or unacceptable toxicity. The study showed that 22 percent of patients responded to the treatment, but continued approval was contingent upon verification and further description of clinical benefit in the IMvigor Phase 3 trial.
The Phase 3 trial, called IMvigor211 (NCT02302807), was a randomized, open-label, multicenter study designed to evaluate the safety and efficacy of Tecentriq versus investigator’s choice of chemotherapy (vinflunine, paclitaxel, or docetaxel) in 931 patients with mUC and progression despite platinum-based chemotherapy.
The study’s primary endpoint was overall survival, assessed in a successive fashion in three study populations defined by their PD-L1 status. The first population tested had the highest levels of PD-L1, the second had any PD-L1 expression, and the third included the overall population.
Secondary endpoints included objective response rate, progression-free survival, duration of response, and proportion of patients with adverse events.
Genentech did not disclose the trial’s data in its release, but reported that the results observed were similar to those obtained in the Phase 2 trial. The company will continue analyzing the trial to understand why the chemotherapy results were better than study assumptions and plans to present full data from the trial later this year.