LONDON, 6 Mar (APM) - AstraZeneca suffered a blow on Friday with the news its Imfinzi combination with tremelimumab failed the Phase III DANUBE trial in a form of metastatic bladder cancer.
José Baselga, head of oncology R&D at AstraZeneca said in a statement
the results from the trial "will inform our comprehensive Phase III development programme in bladder cancer. We look forward to the results of the Phase III NILE trial also in the first-line metastatic setting and we continue to advance clinical trials for patients at earlier stages of the disease."
The company said the Phase III DANUBE trial of Imfinzi (durvalumab) and Imfinzi plus tremelimumab in unresectable, metastatic bladder cancer, did not meet the primary endpoints of improving overall survival (OS) versus standard-of-care chemotherapy for Imfinzi monotherapy in patients whose tumour cells and/or tumour-infiltrating immune cells express high levels of PD-L1, or for Imfinzi plus tremelimumab in patients regardless of their PD-L1 expression.
The safety and tolerability profiles for Imfinzi and the combination with tremelimumab were consistent with previous trials. The data will be presented at a forthcoming medical meeting.
Imfinzi is being developed in patients with unresectable, locally advanced or metastatic bladder cancer in the Phase III NILE trial either in combination with chemotherapy or with chemotherapy and tremelimumab. It is also being tested in earlier stages of bladder cancer in the Phase III NIAGARA trial in combination with chemotherapy, and in the Phase III POTOMAC trial in combination with SoC Bacillus Calmette-Guerin immunotherapy.
The drug is approved in 15 countries, including the U.S., for patients with locally advanced or metastatic bladder cancer previously treated with platinum-containing chemotherapy.
Urothelial cancer (UC), the most common form of bladder cancer, is the 10th most common cancer worldwide and the 13th most common cause of cancer death. PD-L1 is widely expressed in tumour and immune cells in patients with bladder cancer and helps tumours evade detection from the immune system, AstraZeneca said.
The DANUBE trial was conducted in more than 220 centres across 24 countries, including centres in the U.S., Canada, Europe, South America, Asia, Australia and the Middle East.
The primary endpoints of the trial were OS in high PD-L1 patients treated with Imfinzi monotherapy and OS in patients treated with Imfinzi plus tremelimumab regardless of their PD-L1 status.
The DANUBE trial addresses a post-approval commitment in agreement with the U.S. Food and Drug Administration from the May 2017 accelerated approval of Imfinzi in previously treated patients with advanced bladder cancer.
Imfinzi is a human monoclonal antibody that binds to PD-L1 and blocks the interaction of PD-L1 with PD-1 and CD80, countering the tumour's immune-evading tactics and releasing the inhibition of immune responses.
It is approved in the curative-intent setting of unresectable, stage III non-small cell lung cancer (NSCLC) after chemoradiation therapy in 61 countries, including the U.S., Japan, China and Europe, based on the Phase III PACIFIC trial.
Imfinzi recently received its first global approval for the first-line treatment of extensive-stage small cell lung cancer (ES-SCLC) in combination with standard of care chemotherapy in Singapore.
As part of a broad development programme, Imfinzi is also being tested as a monotherapy and in combinations, including with tremelimumab, an anti-CTLA4 monoclonal antibody and potential new medicine, for patients with NSCLC, SCLC, bladder cancer, head and neck cancer, liver cancer, biliary tract cancer, cervical cancer and other solid tumours.
Tremelimumab is a human monoclonal antibody and potential new medicine that targets the activity of cytotoxic T-lymphocyte-associated protein 4 (CTLA-4). It is being tested in a clinical trial programme in combination with Imfinzi in NSCLC, SCLC, bladder cancer, head and neck cancer and liver cancer.