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NCT02516241

Study of MEDI4736 (Durvalumab) With or Without Tremelimumab Versus Standard of Care Chemotherapy in Urothelial Cancer

Active, enrolled Phase 3 Results posted Last updated 28 January 2026
What this trial tests

Phase 3 trial testing MEDI4736 (Durvalumab) in Urothelial Cancer in 1,126 participants. Participants enrolled and being followed up; not accepting new ones.

Timeline
2 November 2015
Primary endpoint
27 January 2020
31 December 2026

Quick facts

Lead sponsorAstraZeneca
PhasePhase 3
StatusActive, enrolled
Study typeINTERVENTIONAL
Allocationrandomized
Designparallel
Maskingnone
Primary purposetreatment
Enrollment1,126
Start date2 November 2015
Primary completion27 January 2020
Estimated completion31 December 2026
Sites222 locations across Italy, Japan, Taiwan, Poland, South Korea, Denmark, Netherlands, Russia

Drugs / interventions tested

Conditions studied

Sponsor

AstraZeneca — full company profile →

Who can join

Adults 18 to 130, any sex, with Urothelial Cancer. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

To Assess the Efficacy of Durvalumab + Tremelimumab Combination Therapy Versus SoC in Terms of OS in Full Analysis Set Primary · From randomization date until death due to any cause, assessed up to the data cut-off date (27JAN2020, a maximum of 5 years).

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.

GroupValue95% CI
Combination Therapy15.113.1 – 18.0
Standard of Care12.110.9 – 14
To Assess the Efficacy of Durvalumab Monotherapy Versus SoC in Terms of OS in PD-L1-High Analysis Set Primary · From randomization date until death due to any cause, assessed up to the data cut-off date (27JAN2020, a maximum of 5 years).

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.

GroupValue95% CI
Monotherapy14.410.4 – 17.3
Standard of Care12.110.4 – 15.0
OS, Full Analysis Set - Durvalumab Monotherapy vs SoC Secondary · From randomization date until death due to any cause, assessed up to the data cut-off date (27JAN2020, a maximum of 5 years).

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.

GroupValue95% CI
Monotherapy13.210.3 – 15
Standard of Care12.110.9 – 14
OS, PD-L1-High Analysis Set -Durvalumab + Tremelimumab Combination Therapy Versus SoC Secondary · From randomization date until death due to any cause, assessed up to the data cut-off date (27JAN2020, a maximum of 5 years).

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.

GroupValue95% CI
Combination Therapy17.914.8 – 24.2
Standard of Care12.110.4 – 15.0
OS, PD-L1-Low/Negative Analysis Set -Durvalumab + Tremelimumab Combination Therapy Versus SoC and Durvalumab + Tremelimumab Combination Therapy Versus Durvalumab Monotherapy Secondary · From randomization date until death due to any cause, assessed up to the data cut-off date (27JAN2020, a maximum of 5 years).

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.

GroupValue95% CI
Combination Therapy11.88.9 – 15.8
Monotherapy10.98.0 – 14.8
Standard of Care12.210.4 – 14
Alive at 24 Months (OS24), Full Analysis Set Secondary · 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) is defined as the Kaplan-Meier estimate of OS at 24 months.

GroupValue95% CI
Combination Therapy39.033.8 – 44.2
Monotherapy31.526.6 – 36.4
Standard of Care29.024.2 – 34.0
Alive at 24 Months (OS24), PD-L1-High Analysis Set Secondary · 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) is defined as the Kaplan-Meier estimate of OS at 24 months.

GroupValue95% CI
Combination Therapy43.736.8 – 50.3
Monotherapy36.029.5 – 42.6
Standard of Care29.323.1 – 35.7
Alive at 24 Months (OS24), PD-L1-Low/Negative Analysis Set Secondary · 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) is defined as the Kaplan-Meier estimate of OS at 24 months.

GroupValue95% CI
Combination Therapy32.124.5 – 40.0
Monotherapy24.517.6 – 32.0
Standard of Care28.621.2 – 36.4
PFS, Full Analysis Set -Durvalumab + Tremelimumab Combination Therapy vs SoC and Durvalumab Mono Therapy vs SoC Secondary · 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).

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.

GroupValue95% CI
Combination Therapy3.73.4 – 3.8
Monotherapy2.31.9 – 3.5
Standard of Care6.75.7 – 7.3
PFS, PD-L1-High Analysis Set -Durvalumab + Tremelimumab Combination Therapy vs SoC and Durvalumab Monotherapy vs SoC Secondary · 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).

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.

GroupValue95% CI
Combination Therapy4.13.6 – 5.7
Monotherapy2.41.9 – 3.7
Standard of Care5.85.6 – 7.2
PFS, PD-L1-Low/Negative Analysis Set -Durvalumab + Tremelimumab Combination Therapy Versus SoC and Durvalumab + Tremelimumab Combination Therapy Versus Durvalumab Monotherapy Secondary · 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).

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.

GroupValue95% CI
Combination Therapy2.01.9 – 3.6
Monotherapy2.01.9 – 3.5
Standard of Care7.25.7 – 7.5
Alive and Progression-free at 12 Months (APF12), Full Analysis Set Secondary · 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).

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.

GroupValue95% CI
Combination Therapy21.417.2 – 26.0
Monotherapy16.813.1 – 21.1
Standard of Care15.311.4 – 19.7

Adverse events — posted to ClinicalTrials.gov

Time frame: From first administration of study treatment up to 90 days after last dose of study medication or date of initiation of the first subsequent therapy, whichever occurs first, approximately 5 years. All-cause mortality, from screening up to data cut-off date (27JAN2020, approximately 5 years).. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Combination Therapy
Serious: 179/340 (53%)
Deaths: 255/342
Monotherapy
Serious: 139/345 (40%)
Deaths: 263/346
Standard of Care
Serious: 125/313 (40%)
Deaths: 270/344

Serious adverse events (278 terms)

ReactionSystemCombination TherapyMonotherapyStandard of Care
Urinary tract infectionInfections and infestations
DiarrhoeaGastrointestinal disorders
PyrexiaGeneral disorders
PneumoniaInfections and infestations
SepsisInfections and infestations
AnaemiaBlood and lymphatic system disorders
Acute kidney injuryRenal and urinary disorders
ColitisGastrointestinal disorders
ConstipationGastrointestinal disorders
UrosepsisInfections and infestations
ThrombocytopeniaBlood and lymphatic system disorders
PyelonephritisInfections and infestations
Platelet count decreasedInvestigations
Pulmonary embolismRespiratory, thoracic and mediastinal disorders
Myocardial infarctionCardiac disorders
VomitingGastrointestinal disorders
DyspnoeaRespiratory, thoracic and mediastinal disorders
PneumonitisRespiratory, thoracic and mediastinal disorders
Febrile neutropeniaBlood and lymphatic system disorders
HypopituitarismEndocrine disorders
Neutrophil count decreasedInvestigations
HaematuriaRenal and urinary disorders
HydronephrosisRenal and urinary disorders
Renal failureRenal and urinary disorders
Chronic obstructive pulmonary diseaseRespiratory, thoracic and mediastinal disorders
Other adverse events (52 terms — click to expand)

ReactionSystemCombination TherapyMonotherapyStandard of Care
AnaemiaBlood and lymphatic system disorders
NauseaGastrointestinal disorders
FatigueGeneral disorders
DiarrhoeaGastrointestinal disorders
PruritusSkin and subcutaneous tissue disorders
NeutropeniaBlood and lymphatic system disorders
ConstipationGastrointestinal disorders
Decreased appetiteMetabolism and nutrition disorders
AstheniaGeneral disorders
PyrexiaGeneral disorders
Urinary tract infectionInfections and infestations
RashSkin and subcutaneous tissue disorders
VomitingGastrointestinal disorders
Neutrophil count decreasedInvestigations
Platelet count decreasedInvestigations
ThrombocytopeniaBlood and lymphatic system disorders
CoughRespiratory, thoracic and mediastinal disorders
ArthralgiaMusculoskeletal and connective tissue disorders
Abdominal painGastrointestinal disorders
Back painMusculoskeletal and connective tissue disorders
HaematuriaRenal and urinary disorders
Oedema peripheralGeneral disorders
Weight decreasedInvestigations
AlopeciaSkin and subcutaneous tissue disorders
HypothyroidismEndocrine disorders
Blood creatinine increasedInvestigations
DyspnoeaRespiratory, thoracic and mediastinal disorders
White blood cell count decreasedInvestigations
DizzinessNervous system disorders
DysgeusiaNervous system disorders
LeukopeniaBlood and lymphatic system disorders
Pain in extremityMusculoskeletal and connective tissue disorders
InsomniaPsychiatric disorders
Dry mouthGastrointestinal disorders
Lipase increasedInvestigations
HiccupsRespiratory, thoracic and mediastinal disorders
HyperthyroidismEndocrine disorders
Alanine aminotransferase increasedInvestigations
HypomagnesaemiaMetabolism and nutrition disorders
Blood alkaline phosphatase increasedInvestigations

Most-reported serious reactions: Urinary tract infection, Diarrhoea, Pyrexia, Pneumonia, Sepsis, Anaemia, Acute kidney injury, Colitis.

Data from ClinicalTrials.gov NCT02516241 adverse events section.

Sponsor's own description

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

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

  1. Pembrolizumab as Second-Line Therapy for Advanced Urothelial Carcinoma.
    Bellmunt J, de Wit R, Vaughn DJ, Fradet Y, et al · · 2017 · cited 2609× · PMID 28212060 · DOI 10.1056/nejmoa1613683
  2. Immune checkpoint inhibitors: recent progress and potential biomarkers.
    Darvin P, Toor SM, Sasidharan Nair V, Elkord E. · · 2018 · cited 1495× · PMID 30546008 · DOI 10.1038/s12276-018-0191-1
  3. Combination strategies with PD-1/PD-L1 blockade: current advances and future directions.
    Yi M, Zheng X, Niu M, Zhu S, et al · · 2022 · cited 1018× · PMID 35062949 · DOI 10.1186/s12943-021-01489-2
  4. Efficacy and Safety of Durvalumab in Locally Advanced or Metastatic Urothelial Carcinoma: Updated Results From a Phase 1/2 Open-label Study.
    Powles T, O'Donnell PH, Massard C, Arkenau HT, et al · · 2017 · cited 660× · PMID 28817753 · DOI 10.1001/jamaoncol.2017.2411
  5. 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.
    Powles T, van der Heijden MS, Castellano D, Galsky MD, et al · · 2020 · cited 386× · PMID 32971005 · DOI 10.1016/s1470-2045(20)30541-6
  6. Tumor immunotherapies by immune checkpoint inhibitors (ICIs); the pros and cons.
    Naimi A, Mohammed RN, Raji A, Chupradit S, et al · · 2022 · cited 350× · PMID 35392976 · DOI 10.1186/s12964-022-00854-y
  7. Antibodies to watch in 2020.
    Kaplon H, Muralidharan M, Schneider Z, Reichert JM. · · 2020 · cited 332× · PMID 31847708 · DOI 10.1080/19420862.2019.1703531
  8. Cold and hot tumors: from molecular mechanisms to targeted therapy.
    Wu B, Zhang B, Li B, Wu H, et al · · 2024 · cited 280× · PMID 39420203 · DOI 10.1038/s41392-024-01979-x

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Drug Landscape aggregates and links these public records for informational use only. Always verify against the primary source before clinical or regulatory decisions. Canonical URL: https://druglandscape.com/trial/NCT02516241.

Primary sources · FDA · ClinicalTrials.gov · EMA · SEC EDGAR · ChEMBL · Wikidata · full sourcing