- A combination of AstraZeneca's cancer drugs Imfinzi and tremelimumab failed to help patients with inoperable bladder cancer live longer than those given chemotherapy, a setback for researchers hoping to use immunotherapies together to improve survival.
- AstraZeneca's trial, dubbed DANUBE, was the first Phase 3 study of two types of immuno-oncology drugs in bladder cancer to report results. Bristol Myers Squibb is expecting data next year on a combination of its therapies Opdivo and Yervoy in a similar setting.
- A study arm testing Imfinzi alone against chemotherapy also failed to significantly extend overall survival, which could spur regulatory review of its earlier accelerated approval for treating the tumor type.
Bladder cancer was the first indication for Imfinzi, and that Food and Drug Administration decision still stands as an "accelerated approval," meaning data from a placebo-controlled study is required to prove the drug's benefit.
The failure of the DANUBE trial has the potential to open FDA review of that decision as a monotherapy, and may close the pathway for a combination approval.
DANUBE tested Imfinzi, a PD-L1 inhibitor, as well as a combination of Imfinzi with tremelimumab, an as-yet unapproved CTLA4 inhibitor, in newly diagnosed urothelial carcinoma. Those two regimens were compared to a chemotherapy combination, with the goal to show Imfinzi-based treatment helped patients survive longer.
While checkpoint inhibitors like Imfinzi, Merck & Co.'s Keytruda and Roche's Tecentriq have won approval in bladder cancer, drugmakers have had difficulty in confirming their benefit in subsequent studies. Use of the drugs by themselves has largely been limited to those patients expressing sufficiently high levels of PD-L1, a biomarker that's correlated with response.
AstraZeneca has more opportunities to confirm Imfinzi's benefit in bladder cancer, however. Its research plan includes the NILE trial, which adds chemotherapy to the immuno-oncology combination; NIAGARA, a chemotherapy combination-only trial; and POTOMAC, a test with Bacillus Calmette-Guerin immunotherapy.
However, the results of DANUBE may not be a good signal for Bristol Myers, which could see results next year from its own combination of Opdivo and Yervoy in a similar setting.
Keytruda's chemotherapy combination trial KEYNOTE-361, meanwhile, could yield results within a couple of months, sending a signal to AstraZeneca whether such a pairing can show benefit over chemo alone. However, the expectations for that may not be high because of the modest benefit observed in Roche's ImVIGOR-130 study.
That data showed a Tecentriq-chemo combination could help keep disease in check, but "were not seen as too compelling," Cantor Fitzgerald analyst Varun Kumar wrote in a Feb. 18 note to clients.