TriangleNCT02516241 · CITED IN SOURCE DOCUMENTS
Study of MEDI4736 (Durvalumab) With or Without Tremelimumab Versus Standard of Care Chemotherapy in Urothelial Cancer
An NCI or FDA source cites this study. A citation does not establish that it applies to an individual diagnosis.
- Phase
- PHASE3
- Status at capture
- ACTIVE NOT RECRUITING
- Registry last update
- 2026-07-14
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
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What did the study report?
Outcomes, safety and baseline populations are separate source sections. Quality-of-life measures appear under their original outcome titles.
Participant flow
Baseline characteristics
To Assess the Efficacy of Durvalumab + Tremelimumab Combination Therapy Versus SoC in Terms of OS in Full Analysis Set
To Assess the Efficacy of Durvalumab Monotherapy Versus SoC in Terms of OS in PD-L1-High Analysis Set
OS, Full Analysis Set - Durvalumab Monotherapy vs SoC
OS, PD-L1-High Analysis Set -Durvalumab + Tremelimumab Combination Therapy Versus SoC
OS, PD-L1-Low/Negative Analysis Set -Durvalumab + Tremelimumab Combination Therapy Versus SoC and Durvalumab + Tremelimumab Combination Therapy Versus Durvalumab Monotherapy
Alive at 24 Months (OS24), Full Analysis Set
Alive at 24 Months (OS24), PD-L1-High Analysis Set
Alive at 24 Months (OS24), PD-L1-Low/Negative Analysis Set
PFS, Full Analysis Set -Durvalumab + Tremelimumab Combination Therapy vs SoC and Durvalumab Mono Therapy vs SoC
PFS, PD-L1-High Analysis Set -Durvalumab + Tremelimumab Combination Therapy vs SoC and Durvalumab Monotherapy vs SoC
PFS, PD-L1-Low/Negative Analysis Set -Durvalumab + Tremelimumab Combination Therapy Versus SoC and Durvalumab + Tremelimumab Combination Therapy Versus Durvalumab Monotherapy
Alive and Progression-free at 12 Months (APF12), Full Analysis Set
Alive and Progression-free at 12 Months (APF12), PD-L1-High Analysis Set
Alive and Progression-free at 12 Months (APF12), PD-L1-Low/Negative Analysis Set
PFS2, Full Analysis Set -Durvalumab + Tremelimumab Combination Therapy vs SoC and Durvalumab Mono Therapy vs SoC
PFS2, PD-L1-High Analysis Set -Durvalumab + Tremelimumab Combination Therapy vs SoC and Durvalumab Monotherapy vs SoC
PFS2, PD-L1-Low/Negative Analysis Set -Durvalumab + Tremelimumab Combination Therapy Versus SoC and Durvalumab + Tremelimumab Combination Therapy Versus Durvalumab Monotherapy
Objective Response Rate (ORR), Full Analysis Set -Durvalumab + Tremelimumab Combination Therapy vs SoC and Durvalumab Mono Therapy vs SoC
Objective Response Rate (ORR), PD-L1-High Analysis Set -Durvalumab + Tremelimumab Combination Therapy vs SoC and Durvalumab Monotherapy vs SoC
Objective Response Rate (ORR), PD-L1-Low/Negative Analysis Set -Durvalumab + Tremelimumab Combination Therapy Versus SoC and Durvalumab + Tremelimumab Combination Therapy Versus Durvalumab Monotherapy
Objective Response Rate (ORR) Based on BICR Assessment According to RECIST 1.1 - Responses Are Confirmed - Durvalumab Cisplatin Ineligible Population
Disease Control Rate (DCR) at 6 Months, Full Analysis Set -Durvalumab + Tremelimumab Combination Therapy vs SoC and Durvalumab Mono Therapy vs SoC
Disease Control Rate (DCR) at 6 Months, PD-L1-High Analysis Set -Durvalumab + Tremelimumab Combination Therapy vs SoC and Durvalumab Monotherapy vs SoC
Disease Control Rate (DCR) at 6 Months, PD-L1-Low/Negative Analysis Set -Durvalumab + Tremelimumab Combination Therapy Versus SoC and Durvalumab + Tremelimumab Combination Therapy Versus Durvalumab Monotherapy
Disease Control Rate (DCR) at 12 Months, Full Analysis Set -Durvalumab + Tremelimumab Combination Therapy vs SoC and Durvalumab Mono Therapy vs SoC
Disease Control Rate (DCR) at 12 Months, PD-L1-High Analysis Set -Durvalumab + Tremelimumab Combination Therapy vs SoC and Durvalumab Monotherapy vs SoC
Disease Control Rate (DCR) at 12 Months, PD-L1-Low/Negative Analysis Set -Durvalumab + Tremelimumab Combination Therapy Versus SoC and Durvalumab + Tremelimumab Combination Therapy Versus Durvalumab Monotherapy
Duration of Response (DoR), Full Analysis Set
Duration of Response (DoR), PD-L1-High Analysis Set
Duration of Response (DoR), PD-L1-Low/Negative Analysis Set
Serum Concentrations of Durvalumab, Pharmacokinetic Analysis Set
Serum Concentrations of Tremelimumab, Pharmacokinetic Analysis Set
Number of Participants With Anti-Drug Antibody (ADA) Response to Durvalumab, Safety Analysis Set - ADA Evaluable Patients
Number of Participants With Anti-Drug Antibody (ADA) Response to Tremelimumab, Safety Analysis Set - ADA Evaluable Patients
Change From Baseline in FACT-BL (Derived NFBlSI-18 Score, FACT-BL TOI, and FACT-BL Total Score) by MMRM Analysis, Full Analysis Set -Durvalumab + Tremelimumab Combination Therapy vs SoC and Durvalumab Mono Therapy vs SoC
Change From Baseline in FACT-BL (Derived NFBlSI-18 Score, FACT-BL TOI, and FACT-BL Total Score) by MMRM Analysis, PD-L1-High Analysis Set -Durvalumab + Tremelimumab Combination Therapy vs SoC and Durvalumab Mono Therapy vs SoC
Change From Baseline in FACT-BL (Derived NFBlSI-18 Score, FACT-BL TOI, and FACT-BL Total Score) by MMRM Analysis, PD-L1-Low/Negative Analysis Set -Durvalumab + Tremelimumab Combination Therapy vs SoC and Durvalumab Mono Therapy vs SoC
Improvement in Fatigue and Deterioration in Pain Per FACT-BL, Full Analysis Set -Durvalumab + Tremelimumab Combination Therapy vs SoC and Durvalumab Mono Therapy vs SoC
Improvement in Fatigue and Deterioration in Pain Per FACT-BL, PD-L1-High Analysis Set -Durvalumab + Tremelimumab Combination Therapy vs SoC and Durvalumab Mono Therapy vs SoC
Improvement in Fatigue and Deterioration in Pain Per FACT-BL, PD-L1-Low/Negative Analysis Set -Durvalumab + Tremelimumab Combination Therapy vs SoC and Durvalumab Mono Therapy vs SoC
Adverse events
Limitations, agreements, and source contact
Who could take part
- eligibility Criteria
- Inclusion Criteria: * 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. Exclusion Criteria: * 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.
- healthy Volunteers
- false
- maximum Age
- 130 Years
- minimum Age
- 18 Years
- sex
- ALL
- std Ages
- ADULT
- OLDER_ADULT
Treatment arms and interventions
- arm Groups
- description
- MEDI4736 (Durvalumab) + Tremelimumab
- intervention Names
- Drug: MEDI4736 (Durvalumab)
- Drug: Tremelimumab
- label
- Combination Therapy
- type
- EXPERIMENTAL
- description
- MEDI4736 (Durvalumab)
- intervention Names
- Drug: MEDI4736 (Durvalumab)
- label
- Monotherapy
- type
- EXPERIMENTAL
- description
- Standard of Care Chemotherapy Treatment
- intervention Names
- Drug: Cisplatin
- Drug: Carboplatin
- Drug: Gemcitabine
- label
- Standard of Care
- type
- ACTIVE_COMPARATOR
- interventions
- arm Group Labels
- Combination Therapy
- Monotherapy
- description
- IV infusion
- name
- MEDI4736 (Durvalumab)
- type
- DRUG
- arm Group Labels
- Combination Therapy
- description
- IV infusion
- name
- Tremelimumab
- type
- DRUG
- arm Group Labels
- Standard of Care
- description
- IV infusion
- name
- Cisplatin
- type
- DRUG
- arm Group Labels
- Standard of Care
- description
- IV infusion
- name
- Carboplatin
- type
- DRUG
- arm Group Labels
- Standard of Care
- description
- IV infusion
- name
- Gemcitabine
- type
- DRUG
Study design
- allocation
- RANDOMIZED
- intervention Model
- PARALLEL
- masking Info
- masking
- NONE
- primary Purpose
- TREATMENT
Enrollment
- count
- 1126
- type
- ACTUAL
Registered outcome plans (not posted results)
- primary Outcomes
- description
- 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.
- measure
- To Assess the Efficacy of Durvalumab + Tremelimumab Combination Therapy Versus SoC in Terms of OS in Full Analysis Set
- time Frame
- From randomization date until death due to any cause, assessed up to the data cut-off date (27JAN2020, a maximum of 5 years).
- description
- 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.
- measure
- To Assess the Efficacy of Durvalumab Monotherapy Versus SoC in Terms of OS in PD-L1-High Analysis Set
- time Frame
- 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
- description
- 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.
- measure
- OS, Full Analysis Set - Durvalumab Monotherapy vs SoC
- time Frame
- From randomization date until death due to any cause, assessed up to the data cut-off date (27JAN2020, a maximum of 5 years).
- description
- 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.
- measure
- OS, PD-L1-High Analysis Set -Durvalumab + Tremelimumab Combination Therapy Versus SoC
- time Frame
- From randomization date until death due to any cause, assessed up to the data cut-off date (27JAN2020, a maximum of 5 years).
- description
- 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.
- measure
- OS, PD-L1-Low/Negative Analysis Set -Durvalumab + Tremelimumab Combination Therapy Versus SoC and Durvalumab + Tremelimumab Combination Therapy Versus Durvalumab Monotherapy
- time Frame
- From randomization date until death due to any cause, assessed up to the data cut-off date (27JAN2020, a maximum of 5 years).
- description
- Alive at 24 months (OS24) is defined as the Kaplan-Meier estimate of OS at 24 months.
- measure
- Alive at 24 Months (OS24), Full Analysis Set
- time Frame
- From randomization date until death due to any cause, assessed up to 24 months or the data cut-off date (27JAN2020).
- description
- Alive at 24 months (OS24) is defined as the Kaplan-Meier estimate of OS at 24 months.
- measure
- Alive at 24 Months (OS24), PD-L1-High Analysis Set
- time Frame
- From randomization date until death due to any cause, assessed up to 24 months or the data cut-off date (27JAN2020).
- description
- Alive at 24 months (OS24) is defined as the Kaplan-Meier estimate of OS at 24 months.
- measure
- Alive at 24 Months (OS24), PD-L1-Low/Negative Analysis Set
- time Frame
- From randomization date until death due to any cause, assessed up to 24 months or the data cut-off date (27JAN2020).
- description
- Progression free survival (PFS) (per RECIST 1.1, as assessed by investigator) was defined as the time from the date of randomization until the date of objective disease progression or death (by any cause in the absence of progression) regardless of whether the patient withdraws from randomized therapy or receives another anticancer therapy prior to progression. Median PFS was calculated using the Kaplan-Meier technique.
- measure
- PFS, Full Analysis Set -Durvalumab + Tremelimumab Combination Therapy vs SoC and Durvalumab Mono Therapy vs SoC
- time Frame
- Tumour scans performed at baseline then every 8 weeks since randomization until confirmed disease progression. Assessed up to the data cut-off date (27JAN2020, a maximum of 5 years).
- description
- Progression free survival (PFS) (per RECIST 1.1, as assessed by investigator) was defined as the time from the date of randomization until the date of objective disease progression or death (by any cause in the absence of progression) regardless of whether the patient withdraws from randomized therapy or receives another anticancer therapy prior to progression. Median PFS was calculated using the Kaplan-Meier technique.
- measure
- PFS, PD-L1-High Analysis Set -Durvalumab + Tremelimumab Combination Therapy vs SoC and Durvalumab Monotherapy vs SoC
- time Frame
- Tumour scans performed at baseline then every 8 weeks since randomization until confirmed disease progression. Assessed up to the data cut-off date (27JAN2020, a maximum of 5 years).
- description
- Progression free survival (PFS) (per RECIST 1.1, as assessed by investigator) was defined as the time from the date of randomization until the date of objective disease progression or death (by any cause in the absence of progression) regardless of whether the patient withdraws from randomized therapy or receives another anticancer therapy prior to progression. Median PFS was calculated using the Kaplan-Meier technique.
- measure
- PFS, PD-L1-Low/Negative Analysis Set -Durvalumab + Tremelimumab Combination Therapy Versus SoC and Durvalumab + Tremelimumab Combination Therapy Versus Durvalumab Monotherapy
- time Frame
- Tumour scans performed at baseline then every 8 weeks since randomization until confirmed disease progression. Assessed up to the data cut-off date (27JAN2020, a maximum of 5 years).
- description
- Alive and progression-free at 12 months (APF12) was defined as the Kaplan-Meier estimate of PFS (per RECIST 1.1 as assessed by investigator) at 12 months.
- measure
- Alive and Progression-free at 12 Months (APF12), Full Analysis Set
- time Frame
- Tumour scans performed at baseline then every 8 weeks since randomization until confirmed disease progression. Assessed up to 12 months or the data cut-off date (27JAN2020).
- description
- Alive and progression-free at 12 months (APF12) was defined as the Kaplan-Meier estimate of PFS (per RECIST 1.1 as assessed by investigator) at 12 months.
- measure
- Alive and Progression-free at 12 Months (APF12), PD-L1-High Analysis Set
- time Frame
- Tumour scans performed at baseline then every 8 weeks since randomization until confirmed disease progression. Assessed up to 12 months or the data cut-off date (27JAN2020).
- description
- Alive and progression-free at 12 months (APF12) was defined as the Kaplan-Meier estimate of PFS (per RECIST 1.1 as assessed by investigator) at 12 months.
- measure
- Alive and Progression-free at 12 Months (APF12), PD-L1-Low/Negative Analysis Set
- time Frame
- Tumour scans performed at baseline then every 8 weeks since randomization until confirmed disease progression. Assessed up to 12 months or the data cut-off date (27JAN2020).
Full study description
- 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
- detailed Description
- This is a randomized, open-label, controlled, multi-center, global Phase III study to determine the efficacy and safety of MEDI4736 (Durvalumab) monotherapy and MEDI4736 (Durvalumab) in combination with tremelimumab versus SoC (cisplatin + gemcitabine or carboplatin + gemcitabine doublet) first-line chemotherapy in treatment-naïve patients with histologically or cytologically documented, unresectable, Stage IV transitional cell carcinoma (transitional cell and mixed transitional/non-transitional cell histologies) of the urothelium (including renal pelvis, ureters, urinary bladder, and urethra) and to allow sufficient flexibility for Investigators and patients to select the agents that reflect their normal clinical practice and national guidelines. The patients enrolled in the study will be randomized 1:1:1 to receive treatment with combination therapy, monotherapy, or SoC (cisplatin + gemcitabine or carboplatin + gemcitabine, based on cisplatin eligibility). Patients will be treated with MEDI4736 (Durvalumab) or MEDI4736 (Durvalumab) with tremelimumab, or treated with SoC until progressive disease (PD) is confirmed, unacceptable toxicity occurs, withdrawal of consent, or another discontinuation criterion is met. Patients will be followed for up to 2 years.
Source references
- references
- citation
- 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.
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Source notices and limitations
Discovery and provenance
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- drawn in 2021 as a first-line therapy for locally advanced or metastatic urothelial cancer. The withdrawal was based on the randomized <a href="/clinicaltrials/NCT02516241">DANUBE</a> trial (NCT02516241) which showed no significant improvement in OS.[<a href="#cit/section_8.65">65</a>][<a href="/Common/PopUps/popDefinition.aspx?i
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- herapy for locally advanced or metastatic urothelial cancer. The withdrawal was based on the randomized <a href="/clinicaltrials/NCT02516241">DANUBE</a> trial (NCT02516241) which showed no significant improvement in OS.[<a href="#cit/section_8.65">65</a>][<a href="/Common/PopUps/popDefinition.aspx?id=810017&version=HealthProf
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- rawn in 2021 as a first-line therapy for locally advanced or metastatic urothelial cancer. The withdrawal was based on the randomized <a href="/clinicaltrials/NCT02516241">DANUBE</a> trial (NCT02516241) which showed no significant improvement in OS.[<a href="#cit/section_9.51">51</a>][<a href="/Common/PopUps/popDefinition.aspx?i
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- erapy for locally advanced or metastatic urothelial cancer. The withdrawal was based on the randomized <a href="/clinicaltrials/NCT02516241">DANUBE</a> trial (NCT02516241) which showed no significant improvement in OS.[<a href="#cit/section_9.51">51</a>][<a href="/Common/PopUps/popDefinition.aspx?id=810017&version=HealthProf
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- Updated: May 2, 2025
- datetime
- 2025-05-02T12:00:00Z
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- May 2, 2025
Preserved source evidence · Not medical advice