AstraZeneca‘s immune checkpoint inhibitor Imfinzi (durvalumab), used alone or in combination with investigational tremelimumab in Phase 3 trial in newly diagnosed people with inoperable and metastatic bladder cancer, failed to improve overall survival compared to standard chemotherapy, the company announced.
The DANUBE trial (NCT02516241) had two main overall survival goals: differences seen between Imfinzi and standard-of-care chemo in patients whose tumors had more than 25% of cells positive for the PD-L1 factor — a biomarker of response to immunotherapies like Imfinzi, and differences seen in the entire trial population (regardless of PD-L1 levels) when patients were treated with a combination of Imfinzi plus tremelimumab.
Neither goal was met.
“AstraZeneca remains committed to addressing unmet needs in bladder cancer and the potential for immunotherapy to improve outcomes for these patients. The results from this trial will inform our comprehensive Phase III development programme in bladder cancer,” José Baselga, executive vice president of oncology research and development, said in a press release.
Imfinzi and tremelimumab — both developed by AstraZeneca — are immune checkpoint inhibitors that work by blocking proteins used by cancer cells to evade the immune system. Imfinzi targets the PD-L1 protein on cancer cells, and tremelimumab targets the CTLA-4 protein on T-cells — immune cells with the ability to fight tumors.
Imfinzi is approved by the U.S. Food and Drug Administration as a second-line therapy for platinum-resistant metastatic bladder cancer, and for certain advanced non-small cell lung cancer patients. It is under investigation in other cancers.
The FDA gave accelerated approval to Imfinzi’s use for bladder cancer based on promising response rates and response duration in the Study 1108 Phase 1/2 trial (NCT01693562). As such, continued permission to use the medicine for bladder cancer may depend on these findings being verified in further trials.
DANUBE was one of the Phase 3 trials designed to confirm Imfinzi’s benefits in these patients. It tested Imfinzi, alone or in combination with tremelimumab, as a first-line treatment for people with cancers of the urinary system, including the ureters, renal pelvis, bladder, and urethra. Eligible patients had to have inoperable cancer with distant spread.
A separate Phase 1 trial l (NCT02261220) found an Imfinzi–tremelimumab combination showed promise in bladder cancer patients as a second-line treatment.
DANUBE enrolled about 1,100 people at some 220 centers across 24 countries. In addition to its primary survival goals, secondary measures included the time patients lived without disease worsening, overall response rates, and safety of the two treatment regimens.
While both primary objectives were not met, the safety and tolerability of the Imfinzi-based regimens were consistent with previous trials, the company reported. AstraZeneca plans to present data at a future medical meeting.
The company is now waiting for results from its NILE Phase 3 trial (NCT03732677), testing Imfinzi plus chemo, with and without tremelimumab, versus chemo alone in patients with advanced bladder cancer.
Two ongoing and recruiting Phase 3 trials — POTOMAC (NCT03528694) and NIAGARA (NCT03732677) — are also testing Imfinzi in earlier stages of bladder cancer.
“We look forward to the results of the Phase 3 NILE trial also in the 1st-line metastatic setting, and we continue to advance clinical trials for patients at earlier stages of the disease,” Baselga said.
