Perioperative Durvalumab With Neoadjuvant ddMVAC or Gemcitabine/Cisplatin in Patients With Muscle-invasive Bladder Cancer (NIAGARA-2)

A Phase IIIb, Open-label, Single-arm, Global Study of Perioperative Durvalumab With Neoadjuvant ddMVAC or Gem/Cis in Patients With Muscle-invasive Bladder Cancer (NIAGARA-2)

The Phase IIIb NIAGARA-2 study aims to expand on the data from the Phase III NIAGARA study by investigating perioperative durvalumab in combination with investigator-selected cisplatin-based neoadjuvant chemotherapy (either ddMVAC or gemcitabine/cisplatin) in a clinical practice setting.

Study Overview

• Status: Recruiting
• Conditions: Urinary Bladder Neoplasms; Methotrexate; Gemcitabine; Cisplatin; Immune Checkpoint Inhibitors; Doxorubicin; Vinblastine
• Intervention / Treatment: Drug: Durvalumab; Drug: Gemcitabine; Drug: Cisplatin; Drug: Durvalumab; Drug: Methotrexate; Drug: Vinblastine; Drug: Doxorubicin

Detailed Description

Not provided

• Study Type: Interventional
• Enrollment (Estimated): 150
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: AstraZeneca Clinical Study Information Center; Phone Number: 1-877-240-9479; Email: information.center@astrazeneca.com

Study Locations

• Australia
  • Chermside, Australia, 4032
    • Recruiting
    • Research Site
  • Elizabeth Vale, Australia, 5112
    • Recruiting
    • Research Site
  • Heidelberg, Australia, 3084
    • Recruiting
    • Research Site
  • Hong Kong, Australia
    • Recruiting
    • Research Site
  • Kogarah, Australia, 2217
    • Recruiting
    • Research Site
  • Macquarie University, Australia, 2109
    • Recruiting
    • Research Site
  • Murdoch, Australia, 6150
    • Recruiting
    • Research Site
  • Port Macquarie, Australia, 2444
    • Recruiting
    • Research Site
  • St Leonards, Australia, 2065
    • Recruiting
    • Research Site
• Brazil
  • Barretos, Brazil, 14784-400
    • Recruiting
    • Research Site
  • Jaú, Brazil, 17210-080
    • Withdrawn
    • Research Site
  • Natal, Brazil, 59075-740
    • Withdrawn
    • Research Site
  • Porto Alegre, Brazil, 91350-200
    • Recruiting
    • Research Site
  • Rio de Janeiro, Brazil, 20230-130
    • Withdrawn
    • Research Site
  • Santo André, Brazil, 09060-650
    • Recruiting
    • Research Site
  • São José do Rio Preto, Brazil, 15090-000
    • Withdrawn
    • Research Site
  • São Paulo, Brazil, 01246-000
    • Recruiting
    • Research Site
• Canada
  • Ontario
    • Hamilton, Ontario, Canada, L8V 5C2
      • Recruiting
      • Research Site
    • London, Ontario, Canada, N6A 5W9
      • Not yet recruiting
      • Research Site
    • Ottawa, Ontario, Canada, K1H 8L6
      • Withdrawn
      • Research Site
  • Quebec
    • Montreal, Quebec, Canada, H3T 1E2
      • Not yet recruiting
      • Research Site
    • Québec, Quebec, Canada, G1J 1Z4
      • Recruiting
      • Research Site
    • Sherbrooke, Quebec, Canada, J1H 5N4
      • Recruiting
      • Research Site
• France
  • Angers, France, 49055
    • Not yet recruiting
    • Research Site
  • Angers, France, 49933
    • Withdrawn
    • Research Site
  • Bordeaux, France, 33075
    • Not yet recruiting
    • Research Site
  • Chambray-lès-Tours, France, 37170
    • Not yet recruiting
    • Research Site
  • Dijon, France, 21079
    • Not yet recruiting
    • Research Site
  • Lille, France, 59037
    • Not yet recruiting
    • Research Site
  • Lyon, France, 69008
    • Not yet recruiting
    • Research Site
  • Marseille, France, 13009
    • Not yet recruiting
    • Research Site
  • Montpellier, France, 34070
    • Not yet recruiting
    • Research Site
  • Nice, France, 06189
    • Not yet recruiting
    • Research Site
  • Nîmes, France, 30029
    • Not yet recruiting
    • Research Site
  • Paris, France, 75010
    • Not yet recruiting
    • Research Site
  • Paris, France, 75900
    • Not yet recruiting
    • Research Site
  • Pierre-Bénite, France, 69310
    • Not yet recruiting
    • Research Site
  • Poitiers, France, 86021
    • Not yet recruiting
    • Research Site
  • Quint-Fonsegrives, France, 31130
    • Not yet recruiting
    • Research Site
  • Rennes, France, 35000
    • Not yet recruiting
    • Research Site
  • Rouen, France, 76230
    • Not yet recruiting
    • Research Site
  • Strasbourg, France, 67033
    • Not yet recruiting
    • Research Site
  • Suresnes, France, 92150
    • Not yet recruiting
    • Research Site
• Italy
  • Florence, Italy, 50139
    • Not yet recruiting
    • Research Site
  • Orbassano, Italy, 10043
    • Not yet recruiting
    • Research Site
  • Roma, Italy, 00144
    • Not yet recruiting
    • Research Site
• Netherlands
  • Amsterdam, Netherlands, 1066CX
    • Not yet recruiting
    • Research Site
  • Nijmegen, Netherlands, 6500 HB
    • Not yet recruiting
    • Research Site
  • Rotterdam, Netherlands, 3015 GD
    • Not yet recruiting
    • Research Site
• Spain
  • Barcelona, Spain, 08035
    • Not yet recruiting
    • Research Site
  • Barcelona, Spain, 08036
    • Not yet recruiting
    • Research Site
  • Barcelona, Spain, 8003
    • Not yet recruiting
    • Research Site
  • Barcelona, Spain, 08025
    • Not yet recruiting
    • Research Site
  • Girona, Spain, 17007
    • Not yet recruiting
    • Research Site
  • Las Palmas de Gran Canaria, Spain, 35016
    • Not yet recruiting
    • Research Site
  • Lugo, Spain, 27003
    • Not yet recruiting
    • Research Site
  • Madrid, Spain, 28040
    • Not yet recruiting
    • Research Site
  • Madrid, Spain, 28033
    • Not yet recruiting
    • Research Site
  • Santiago de Compostela, Spain, 15706
    • Not yet recruiting
    • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Participants with clinical tumour stage T2-T4aN0/1M0 or T1N1M0 with transitional or mixed transitional cell histology
• Patients must be planning to undergo radical cystectomy
• Patients who have not received prior systemic chemotherapy or immunotherapy for treatment of muscle-invasive bladder cancer
• ECOG performance status of 0 or 1
• Minimum life expectancy of 12 weeks at first dose of study medication

Exclusion criteria:

• Evidence of lymph node (N2-N3) or metastatic (M1) disease
• Inoperable tumour(s) with fixation to the pelvic wall on clinical examination
• Prior exposure to immune-mediated therapy including, but not limited to, other anti CTLA-4, anti-PD 1, anti-PD L1 and anti-PD-L2 antibodies, excluding Bacillus Calmette-Guérin
• Current or prior use of immunosuppressive medication within 14 days before the first dose of durvalumab
• Any concomitant medication known to be contraindicated to the chemotherapy (ddMVAC or gem/cis).
• Uncontrolled intercurrent illness.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: ddMVAC cohort; Durvalumab + chemotherapy	Drug: Durvalumab; Anti- PD-L1 Antibody; Drug: Cisplatin; Chemotherapy agent; Drug: Durvalumab; Anti- PD-L1 Antibody.; Drug: Methotrexate; Chemotherapy agent.; Drug: Vinblastine; Chemotherapy agent; Drug: Doxorubicin; Chemotherapy agent
Experimental: gem/cis cohort; Durvalumab + chemotherapy	Drug: Durvalumab; Anti- PD-L1 Antibody; Drug: Gemcitabine; Chemotherapy agent; Drug: Cisplatin; Chemotherapy agent; Drug: Durvalumab; Anti- PD-L1 Antibody.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The safety of neoadjuvant durvalumab combined with ddMVAC or gem/cis prior to radical cystectomy (RC).	Incidence of Grade 3 or 4 [possibly treatment-related adverse events (PRAEs)] as observed prior to RC.	Up to 6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The safety and tolerability of perioperative durvalumab combined with ddMVAC or gem/cis.	Incidence, severity, nature, seriousness, intervention/treatment, outcome, and causality of treatment-emergent adverse events, including PRAEs, adverse events of special interest, immune-mediated adverse events, adverse events (AEs), and serious adverse events; AEs resulting in study treatment interruption and discontinuation; laboratory findings.	Up to 2 years
The efficacy of perioperative durvalumab combined with ddMVAC or gem/cis in terms of event-free survival (EFS).	EFS is defined as the time from first neoadjuvant durvalumab + chemotherapy treatment until the earliest occurrence of any of the following events: First recurrence of disease after RC; First documented progression in participants who were medically precluded from RC; Time of expected surgery in participants who refuse to undergo RC or failure to undergo RC in participants with residual disease; Death due to any cause.	Up to 3 years
The efficacy of perioperative durvalumab combined with ddMVAC or gem/cis in terms of disease-free survival (DFS).	DFS is defined as the time from the date of RC to the earliest of the first recurrence of disease post RC or death due to any cause.	Up to 3 years
The efficacy of perioperative durvalumab combined with ddMVAC or gem/cis in terms of OS.	OS is defined as the time from first neoadjuvant durvalumab + chemotherapy until death due to any cause.	Up to 3 years
The efficacy of neoadjuvant durvalumab combined with ddMVAC or gem/cis followed by RC in terms of pathologic complete response (pCR).	pCR rate is defined as the proportion of participants whose pathologic staging is T0N0M0 as assessed per local pathology review using specimens obtained via RC.	Up to 3 years
The efficacy of neoadjuvant durvalumab combined with ddMVAC or gem/cis followed by RC in terms of pathologic downstaging (pDS).	pDS rate is defined as the proportion of participants whose pathologic staging is <P2 per local pathology review using specimens obtained via RC.	Up to 3 years

Collaborators and Investigators

• Sponsor: AstraZeneca

Study record dates

Study Major Dates

• Study Start (Actual): May 15, 2025
• Primary Completion (Estimated): October 31, 2028
• Study Completion (Estimated): October 31, 2028

Study Registration Dates

• First Submitted: April 29, 2025
• First Submitted That Met QC Criteria: April 29, 2025
• First Posted (Actual): May 7, 2025

Study Record Updates

• Last Update Posted (Actual): June 11, 2026
• Last Update Submitted That Met QC Criteria: June 10, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Keywords: Gemcitabine; Immunotherapy; Cisplatin; Bladder Cancer; Durvalumab; Muscle-invasive Bladder Cancer; Perioperative Durvalumab; ddMVAC
• Additional Relevant MeSH Terms: Urogenital Diseases; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Male Urogenital Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urologic Neoplasms; Urinary Bladder Diseases; Urinary Bladder Neoplasms; Organic Chemicals; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Hydrocarbons; Hydrocarbons, Cyclic; Carbohydrates; Alkaloids; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Polycyclic Compounds; Glycosides; Indoles; Inorganic Chemicals; Chlorine Compounds; Nitrogen Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Pterins; Pteridines; Vinca Alkaloids; Secologanin Tryptamine Alkaloids; Indole Alkaloids; Indolizidines; Indolizines; Aminopterin; Anthracyclines; Naphthacenes; Aminoglycosides; Platinum Compounds; Daunorubicin; Gemcitabine; Methotrexate; Doxorubicin; Cisplatin; Vinblastine; durvalumab
• Other Study ID Numbers: D933RC00002

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal Vivli.org. All requests will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.

Yes, indicates that AZ are accepting requests for IPD, but this does not mean all requests will be shared.

• IPD Sharing Time Frame: AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA PhRMA Data Sharing Principles. For details of our timelines, please refer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
• IPD Sharing Access Criteria: When a request has been approved AstraZeneca will provide access to the anonymized individual patient-level data via secure research environment Vivli.org. Signed Data Usage Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes