# AstraZeneca Phase III DANUBE did not meet the primary endpoints

- Link: https://www.directorstalkinterviews.com/astrazeneca-phase-iii-danube-did-not-meet-the-primary-endpoints/412807784
- Published: 2020-03-06T07:25:32+00:00
- Author: Amilia Stone

**[AstraZeneca PLC](https://www.directorstalkinterviews.com/ftse-company/astrazeneca/azn.l)**(
[LON:AZN](https://www.directorstalkinterviews.com/ftse-company/astrazeneca/azn.l))
has today updated on the Phase III DANUBE trial in bladder cancer.

The Phase III DANUBE trial for _Imfinzi_ (durvalumab) and _Imfinzi_ plus tremelimumab
in unresectable, Stage IV (metastatic) bladder cancer did not meet the primary endpoints
of improving overall survival (OS) versus standard-of-care (SoC) chemotherapy for
_Imfinzi_ monotherapy in patients whose tumour cells and/or tumour-infiltrating 
immune cells express high levels (≥25%) 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. _Imfinzi_ 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.

_Imfinzi_ is approved for patients with locally advanced or metastatic bladder cancer
previously treated with platinum-containing chemotherapy in 15 countries, including
the US.

**Bladder cancer**

In 2018, approximately 550,000 people were diagnosed with bladder cancer around 
the world and 200,000 died from the disease.^(1) Locally advanced and metastatic
bladder cancer remains an area of unmet medical need and typically only one in seven
patients are alive five years after diagnosis.^(2) Urothelial cancer (UC) is the
most common form of bladder cancer.^(3) UC is the 10th most common cancer worldwide
and the 13th most common cause of cancer death.^(1,4) PD-L1 is widely expressed 
in tumour and immune cells in patients with bladder cancer and helps tumours evade
detection from the immune system.^(5)

**DANUBE**

DANUBE is a randomised, open-label, multi-centre, global, Phase III trial in the
1st-line treatment of both cisplatin eligible and ineligible patients with unresectable,
Stage IV (metastatic) UC. The trial compared _Imfinzi_ monotherapy or _Imfinzi_ 
plus tremelimumab versus cisplatin and gemcitabine or carboplatin and gemcitabine
chemotherapy. The trial was conducted in more than 220 centres across 24 countries,
including centres in the US, Canada, Europe, South America, Asia, Australia and 
the Middle East.

Eligible patients included those with transitional cell carcinoma of the urothelium,
including renal pelvis, ureters, urinary bladder, and urethra. High PD-L1 was defined
as ≥25% of tumour cells (TC) or tumour-infiltrating immune cells (IC) expressing
membrane PD-L1 if ICs involved >1% of the tumour area, or TC≥25% or IC=100% if ICs
involved ≤1% of the tumour area.

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 US Food and Drug Administration from the May 2017 accelerated
US approval of _Imfinzi_ in previously treated patients with advanced bladder cancer.

**Imfinzi**

_Imfinzi_ (durvalumab) 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.

_Imfinzi _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 US, Japan, China and across the EU, based on the Phase III PACIFIC
trial. _Imfinzi_ recently received its first global approval for the 1st-line treatment
of extensive-stage small cell lung cancer (ES-SCLC) in combination with SoC 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, as a treatment for patients with NSCLC, SCLC, bladder
cancer, head and neck cancer, liver cancer, biliary tract cancer, cervical cancer
and other solid tumours.

**Tremelimumab**

Tremelimumab is a human monoclonal antibody and potential new medicine that targets
the activity of cytotoxic T-lymphocyte-associated protein 4 (CTLA-4). Tremelimumab
blocks the activity of CTLA-4, contributing to T cell activation, priming the immune
response to cancer and fostering cancer cell death. Tremelimumab is being tested
in a clinical trial programme in combination with _Imfinzi_ in NSCLC, SCLC, bladder
cancer, head and neck cancer and liver cancer.

> **José Baselga, Executive Vice President, Oncology R&D, said**: “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. We look forward
> to the results of the Phase III NILE trial also in the 1st-line metastatic setting,
> and we continue to advance clinical trials for patients at earlier stages of the
> disease.”

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