Study of MEDI4736 (Durvalumab) With or Without Tremelimumab Versus Standard of Care Chemotherapy in Urothelial Cancer
A Phase III, Randomized, Open-Label, Controlled, Multi-Center, Global Study of First-Line MEDI4736 (Durvalumab) Monotherapy and MEDI4736 (Durvalumab) in Combination With Tremelimumab Versus Standard of Care Chemotherapy in Patients With Unresectable Stage IV Urothelial Cancer
2 other identifiers
interventional
1,126
23 countries
217
Brief Summary
A Phase III, Randomized, Open-Label, Controlled, Multi-Center, Global Study of First-Line MEDI4736 (Durvalumab) Monotherapy and MEDI4736 (Durvalumab) in Combination with Tremelimumab Versus Standard of Care Chemotherapy in Patients with Stage IV Urothelial Cancer
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_3
Started Nov 2015
Longer than P75 for phase_3
217 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
July 13, 2015
CompletedFirst Posted
Study publicly available on registry
August 5, 2015
CompletedStudy Start
First participant enrolled
November 2, 2015
CompletedPrimary Completion
Last participant's last visit for primary outcome
January 27, 2020
CompletedResults Posted
Study results publicly available
May 13, 2021
CompletedStudy Completion
Last participant's last visit for all outcomes
December 31, 2026
ExpectedApril 20, 2026
April 1, 2026
4.2 years
July 13, 2015
January 25, 2021
April 17, 2026
Conditions
Keywords
Outcome Measures
Primary Outcomes (2)
To Assess the Efficacy of Durvalumab + Tremelimumab Combination Therapy Versus SoC in Terms of OS in Full Analysis Set
The OS was defined as the time from the date of randomization until death due to any cause (ie, date of death or censoring - date of randomization + 1). Any participant not known to have died at the time of analysis were censored based on the last recorded date on which the participant was known to be alive. Median OS was calculated using the Kaplan-Meier technique.
From randomization date until death due to any cause, assessed up to the data cut-off date (27JAN2020, a maximum of 5 years).
To Assess the Efficacy of Durvalumab Monotherapy Versus SoC in Terms of OS in PD-L1-High Analysis Set
The OS was defined as the time from the date of randomization until death due to any cause (ie, date of death or censoring - date of randomization + 1). Any participant not known to have died at the time of analysis were censored based on the last recorded date on which the participant was known to be alive. Median OS was calculated using the Kaplan-Meier technique.
From randomization date until death due to any cause, assessed up to the data cut-off date (27JAN2020, a maximum of 5 years).
Secondary Outcomes (38)
OS, Full Analysis Set - Durvalumab Monotherapy vs SoC
From randomization date until death due to any cause, assessed up to the data cut-off date (27JAN2020, a maximum of 5 years).
OS, PD-L1-High Analysis Set -Durvalumab + Tremelimumab Combination Therapy Versus SoC
From randomization date until death due to any cause, assessed up to the data cut-off date (27JAN2020, a maximum of 5 years).
OS, PD-L1-Low/Negative Analysis Set -Durvalumab + Tremelimumab Combination Therapy Versus SoC and Durvalumab + Tremelimumab Combination Therapy Versus Durvalumab Monotherapy
From randomization date until death due to any cause, assessed up to the data cut-off date (27JAN2020, a maximum of 5 years).
Alive at 24 Months (OS24), Full Analysis Set
From randomization date until death due to any cause, assessed up to 24 months or the data cut-off date (27JAN2020).
Alive at 24 Months (OS24), PD-L1-High Analysis Set
From randomization date until death due to any cause, assessed up to 24 months or the data cut-off date (27JAN2020).
- +33 more secondary outcomes
Study Arms (3)
Combination Therapy
EXPERIMENTALMEDI4736 (Durvalumab) + Tremelimumab
Monotherapy
EXPERIMENTALMEDI4736 (Durvalumab)
Standard of Care
ACTIVE COMPARATORStandard of Care Chemotherapy Treatment
Interventions
Eligibility Criteria
You may qualify if:
- Patients with histologically or cytologically documented, unresectable, Stage IV transitional cell carcinoma of the urothelium who have not been previously treated with first-line chemotherapy.
- Patients eligible or ineligible for cisplatin-based chemotherapy. Cisplatin ineligibility is defined as meeting 1 of the following criteria: • Creatinine clearance (calculated or measured) \<60 mL/min calculated by Cockcroft-Gault equation (using actual body weight) or by measured 24-hour urine collection for determination • Common Terminology Criteria for Adverse Events (CTCAE) Grade ≥2 audiometric hearing loss • CTCAE Grade ≥2 peripheral neuropathy • New York Heart Association ≥Class III heart failure.
- Tumor PD-L1 status, with Immunohistochemical (IHC) assay confirmed by a reference laboratory, must be known prior to randomization.
You may not qualify if:
- Prior exposure to immune-mediated therapy, including but not limited to, other anti cytotoxic T-lymphocyte-associated protein 4 (CTLA 4), anti-PD-1, anti-PD-L1, or anti-PD-L2 antibodies, including therapeutic anticancer vaccines. Prior local intervesical chemotherapy or immunotherapy is allowed if completed at least 28 days prior to the initiation of study treatment.
- History of allogenic organ transplantation that requires use of immunosuppressive agents.
- Active or prior documented autoimmune or inflammatory disorders. The following are exceptions to this criterion: • Patients with vitiligo or alopecia • Patients with hypothyroidism (eg, following Hashimoto syndrome) stable on hormone replacement • Any chronic skin condition that does not require systemic therapy • Patients without active disease in the last 3 years may be included but only after consultation with AstraZeneca • Patients with celiac disease controlled by diet alone may be included but only after consultation with AstraZeneca.
- Brain metastases or spinal cord compression unless the patient's condition is stable and off steroids for at least 14 days prior to the start of study treatment. Patients with suspected or known brain metastases at screening should have an MRI (preferred)/CT, preferably with IV contrast to access baseline disease status.
- Active infection including tuberculosis, hepatitis B, hepatitis C, or human immunodeficiency virus (HIV).
- Current or prior use of immunosuppressive medication within 14 days before the first dose of investigational product (IP). The following are exceptions to this criterion: • Intranasal, inhaled, topical steroids, or local steroid injections (eg, intra articular injection) • Systemic corticosteroids at physiologic doses not to exceed 10 mg/day of prednisone or its equivalent • Steroids as premedication for hypersensitivity reactions (eg, CT scan premedication).
- Receipt of live attenuated vaccine within 30 days prior to the first dose of IP. Note: Patients, if enrolled, should not receive live vaccine during the study and up to 30 days after the last dose of IP.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- AstraZenecalead
Study Sites (222)
Research Site
Los Angeles, California, 90095, United States
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Stanford, California, 94305, United States
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Aurora, Colorado, 80045, United States
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New Haven, Connecticut, 06520, United States
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Tampa, Florida, 33612, United States
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Atlanta, Georgia, 30322, United States
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Louisville, Kentucky, 40202, United States
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Boston, Massachusetts, 02215, United States
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Ann Arbor, Michigan, 48109, United States
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Detroit, Michigan, 48201, United States
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Omaha, Nebraska, 68130, United States
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New York, New York, 10021, United States
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New York, New York, 10029, United States
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Memphis, Tennessee, 38120, United States
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Nashville, Tennessee, 37203, United States
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Seattle, Washington, 98101, United States
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Box Hill, 3128, Australia
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Elizabeth Vale, 5112, Australia
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Macquarie University, 2109, Australia
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St Leonards, 2065, Australia
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Waratah, 2298, Australia
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Linz, 4010, Austria
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Vienna, 1090, Austria
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Vienna, 1140, Austria
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Brussels, 1000, Belgium
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Brussels, 1200, Belgium
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Leuven, 3000, Belgium
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Liège, 4000, Belgium
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Barretos, 14784-400, Brazil
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Belo Horizonte, 30380-472, Brazil
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Ijuí, 98700-000, Brazil
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Itajaí, 88301-220, Brazil
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Porto Alegre, 90035-003, Brazil
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Porto Alegre, 90610-000, Brazil
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Porto Alegre, 91350-200, Brazil
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Rio de Janeiro, 20231-050, Brazil
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Rio de Janeiro, 22793-080, Brazil
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São José do Rio Preto, 15090-000, Brazil
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São Paulo, 01209-000, Brazil
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São Paulo, 01321-001, Brazil
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São Paulo, 01509-900, Brazil
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Calgary, Alberta, T2N 4N2, Canada
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Edmonton, Alberta, T6G 1Z2, Canada
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Kelowna, British Columbia, V1Y 5L3, Canada
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Vancouver, British Columbia, V5Z 4E6, Canada
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Halifax, Nova Scotia, B3H 1V7, Canada
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Hamilton, Ontario, L8V 5C2, Canada
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Newmarket, Ontario, L3Y 2P9, Canada
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Oshawa, Ontario, L1G 2B9, Canada
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Ottawa, Ontario, K1H 1C4, Canada
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Toronto, Ontario, M4N 3M5, Canada
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Toronto, Ontario, M5G 2M9, Canada
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Québec, Quebec, G1R 3S1, Canada
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Sherbrooke, Quebec, J1H 5N4, Canada
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Beijing, 100034, China
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Beijing, 100039, China
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Beijing, 100191, China
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Changchun, 130012, China
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Changsha, 410013, China
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Chongqing, 400038, China
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Hangzhou, 310009, China
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Hangzhou, 310014, China
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Nanjing, 210008, China
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Shanghai, 200000, China
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Shanghai, 200032, China
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Shanghai, 200072, China
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Shanghai, 200080, China
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Shanghai, 200127, China
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Shenyang, 110001, China
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Tianjin, 300211, China
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Xi'an, 710061, China
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Xiamen, 361003, China
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Århus C, 8000, Denmark
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Herlev, 2730, Denmark
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København Ø, 2100, Denmark
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Odense C, 5000, Denmark
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Bordeaux, 33000, France
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Bordeaux, 33076, France
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Caen, 14076, France
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Lyon, 69008, France
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Marseille, 13273, France
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Paris, 75475, France
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Poitiers, 86021, France
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Suresnes, 92151, France
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Toulouse, 31059, France
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Villejuif, 94805, France
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Düsseldorf, 40225, Germany
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Erlangen, 91054, Germany
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Hanover, 30625, Germany
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Heidelberg, 69120, Germany
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Jena, 07747, Germany
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München, 81675, Germany
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Münster, 48149, Germany
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Athens, 11528, Greece
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Athens, 14564, Greece
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Heraklion, 71110, Greece
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Holargos, Athens, 155 62, Greece
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Maroussi, Athens, 15125, Greece
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Pátrai, 26500, Greece
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Thessaloniki, 56 429, Greece
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Haifa, 31096, Israel
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Jerusalem, 91120, Israel
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Petah Tikva, 4941492, Israel
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Ramat Gan, 5265601, Israel
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Ẕerifin, 70300, Israel
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Arezzo, 52100, Italy
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Meldola, 47014, Italy
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Milan, 20132, Italy
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Milan, 20133, Italy
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Naples, 80131, Italy
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Orbassano, 10043, Italy
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Pavia, 27100, Italy
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Roma, 00152, Italy
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San Giovanni Rotondo, 71013, Italy
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Akita, 010-8543, Japan
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Bunkyō City, 113-8603, Japan
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Fukuoka, 811-1347, Japan
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Hakata-shi, 812-0033, Japan
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Hirosaki-shi, 036-8563, Japan
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Hiroshima, 730-8518, Japan
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Izumo-shi, 693-8501, Japan
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Kagoshima, 890-8520, Japan
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Kanazawa, 920-8641, Japan
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Kita-gun, 761-0793, Japan
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Kobe, 650-0047, Japan
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Koshigaya-shi, 343-8555, Japan
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Kōtoku, 135-8550, Japan
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Kumamoto, 860-0008, Japan
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Kyoto, 606-8507, Japan
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Matsuyama, 791-0280, Japan
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Morioka, 028-3695, Japan
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Nagasaki, 852-8501, Japan
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Nagoya, 460-0001, Japan
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Nagoya, 466-8560, Japan
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Osaka, 541-8567, Japan
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Osaka, 545-8586, Japan
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Osakasayama-shi, 589-8511, Japan
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Saga, 840-8571, Japan
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Sagamihara-shi, 252-0315, Japan
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Sakura-shi, 285-8741, Japan
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Sapporo, 060-8648, Japan
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Suita-shi, 565-0871, Japan
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Takatsuki-shi, 569-8686, Japan
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Yokohama, 232-0024, Japan
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Yokohama, 236-0004, Japan
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Guadalajara, 44280, Mexico
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León, 37000, Mexico
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Mexico City, 01120, Mexico
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México, 04739, Mexico
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México, 06760, Mexico
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Monterrey, 64460, Mexico
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Amsterdam, 1066 CX, Netherlands
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Amsterdam, 1081 HV, Netherlands
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Breda, 4819 EV, Netherlands
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Enschede, 7512 KZ, Netherlands
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Groningen, 9713 GZ, Netherlands
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Leiden, 2333 ZA, Netherlands
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Maastricht, 6229 HX, Netherlands
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Nijmegen, 6525 GA, Netherlands
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Gdansk, 80-462, Poland
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Gdansk, 80-952, Poland
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Gdynia, 81-519, Poland
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Gliwice, 44-101, Poland
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Olsztyn, 10-228, Poland
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Otwock, 05-400, Poland
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Szczecin, 70-111, Poland
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Warsaw, 02-781, Poland
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Lisbon, 1649-035, Portugal
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Loures, 2674-514, Portugal
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Porto, 4099-001, Portugal
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Moscow, 105229, Russia
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Moscow, 115478, Russia
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Murmansk, 183047, Russia
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Nizhnyi Novgorod, 603001, Russia
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Obninsk, 249036, Russia
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Omsk, 644013, Russia
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Saint Petersburg, 191014, Russia
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Saint Petersburg, 191015, Russia
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Saint Petersburg, 194354, Russia
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Saint Petersburg, 197758, Russia
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Saint Petersburg, 199178, Russia
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Ufa, 450054, Russia
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Yaroslavl, 150054, Russia
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Incheon, 21565, South Korea
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Seongnam-si, 13620, South Korea
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Seoul, 02841, South Korea
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Seoul, 03080, South Korea
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Seoul, 03722, South Korea
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Seoul, 05505, South Korea
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Seoul, 6351, South Korea
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Badajoz, 06008, Spain
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Badalona, 08916, Spain
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Barcelona, 08003, Spain
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Barcelona, 08243, Spain
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Elche(Alicante), 03202, Spain
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Madrid, 08035, Spain
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Madrid, 28007, Spain
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Madrid, 28040, Spain
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Madrid, 28041, Spain
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Madrid, 28050, Spain
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Pozuelo de Alarcón, 28223, Spain
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Santiago de Compostela, 15706, Spain
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Seville, 41013, Spain
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Kaohsiung City, Taiwan
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Taichung, 00407, Taiwan
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Tainan, 704, Taiwan
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Taipei, 10002, Taiwan
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Taipei, 112, Taiwan
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Taoyuan, 333, Taiwan
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Ankara, 06230, Turkey (Türkiye)
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Edirne, 22030, Turkey (Türkiye)
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Izmir, 35100, Turkey (Türkiye)
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Cambridge, CB2 0QQ, United Kingdom
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Cardiff, CF14 2TL, United Kingdom
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Glasgow, G12 0YN, United Kingdom
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Leeds, LS9 7TF, United Kingdom
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London, E1 1BB, United Kingdom
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London, SE1 9RT, United Kingdom
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Manchester, M20 4BX, United Kingdom
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Metropolitan Borough of Wirral, CH63 4JY, United Kingdom
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Sheffield, S10 2SJ, United Kingdom
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Southampton, SO16 6YD, United Kingdom
Related Publications (1)
Powles T, van der Heijden MS, Castellano D, Galsky MD, Loriot Y, Petrylak DP, Ogawa O, Park SH, Lee JL, De Giorgi U, Bogemann M, Bamias A, Eigl BJ, Gurney H, Mukherjee SD, Fradet Y, Skoneczna I, Tsiatas M, Novikov A, Suarez C, Fay AP, Duran I, Necchi A, Wildsmith S, He P, Angra N, Gupta AK, Levin W, Bellmunt J; DANUBE study investigators. Durvalumab alone and durvalumab plus tremelimumab versus chemotherapy in previously untreated patients with unresectable, locally advanced or metastatic urothelial carcinoma (DANUBE): a randomised, open-label, multicentre, phase 3 trial. Lancet Oncol. 2020 Dec;21(12):1574-1588. doi: 10.1016/S1470-2045(20)30541-6. Epub 2020 Sep 21.
PMID: 32971005DERIVED
Related Links
MeSH Terms
Interventions
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Medical Science Director
- Organization
- AstraZeneca
Publication Agreements
- PI is Sponsor Employee
- No
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
July 13, 2015
First Posted
August 5, 2015
Study Start
November 2, 2015
Primary Completion
January 27, 2020
Study Completion (Estimated)
December 31, 2026
Last Updated
April 20, 2026
Results First Posted
May 13, 2021
Record last verified: 2026-04
Data Sharing
- IPD Sharing
- Will share
- Shared Documents
- STUDY PROTOCOL, SAP
- Time Frame
- AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA Pharma Data Sharing Principles. For details of our timelines, please rerefer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
- Access Criteria
- When a request has been approved AstraZeneca will provide access to the de-identified individual patient-level data in an approved sponsored tool . Signed Data Sharing Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information. Additionally, all users will need to accept the terms and conditions of the SAS MSE to gain access. For additional details, please review the Disclosure Statements at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All request will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.