Bladder cancer may have been the first FDA-approved indication for Tecentriq—as the first PD-1/L1 inhibitor to enter the area—but that doesn’t mean the Roche drug can always win there.
Tecentriq failed a solo trial aimed at reducing the risk of cancer progressing or returning in patients with muscle-invasive urothelial cancer (MIUC) who had undergone surgery, Roche said Friday.
In the phase 3 trial, Tecentriq didn’t show benefit when compared with simple observation at delaying the time to cancer recurrence or death, the study’s primary endpoint.
MIUC is a type of bladder cancer in which cancer has spread into the muscle wall of the bladder but not yet to other parts of the body. It’s an intermediate stage between non-muscle invasive bladder cancer and more severe metastatic disease, accounting for about 25% of newly diagnosed cases.
In 2016, Tecentriq became the first product in the PD-1/L1 inhibitor class approved for any type of bladder cancer based on data from the IMvigor210 study. The indication was for the treatment of patients with locally advanced or metastatic urothelial carcinoma following platinum-containing chemo.
But moving into 2017, data showed that in the phase 3 IMvigor211 trial, Tecentriq had failed to beat out chemo at extending those patients’ lives, endangering its FDA go-ahead. Despite the lack of an overall survival benefit, though—considered the gold standard when it comes to evaluating cancer drugs—Roche did get to keep that accelerated approval.
Shortly before that bad news, Tecentriq nabbed an additional nod for those who are not eligible for initial cisplatin chemo. However, in mid-2018, the FDA limited that use to only those whose tumors express biomarker PD-L1. The agency added that restriction after noticing that both Tecentriq and Merck & Co.’s PD-1 leader Keytruda may perform worse than chemo at prolonging the lives of some previously untreated bladder cancer patients.
IMvigor010, the MIUC study, isn’t the first outright trial failure Tecentriq has chalked up in bladder cancer, either. In April 2019, the Swiss drugmaker unveiled it had scrapped a phase 1 Tecentriq trial in non-muscle invasive bladder cancer (NMIBC), a field in which Keytruda recently racked up the first FDA green light for the PD-1/L1 class. That nod came for patients who are unresponsive to standard Bacillus Calmette-Guerin (BCG) treatment.
Things looked promising in August, when Roche said a combination of Tecentriq and chemo had topped chemo alone among newly diagnosed metastatic bladder cancer patients.
However, at the European Society for Medical Oncology annual meeting in September, investigator Ignacio Durán, M.D., cautioned that the 18% reduction in the risk of disease progression or death Tecentriq had posted in the IMvigor130 trial wouldn’t be enough for an approval, even though it crossed the statistical significance bar. Not all is lost, though, as Roche is still collecting data to assess an overall survival benefit, the study’s other primary endpoint.
Roche is also testing Tecentriq in other bladder cancer trials. For one, it’s pitting a combo of Tecentriq and BCG against BCG vaccine alone in BCG-naïve NMIBC patients in the Alban trial, which is expected to read out mid-2022.