Muscle Invasive Bladder CancerPhase 3VOLGANCT04960709
Treatment Combination of Durvalumab, Tremelimumab and Enfortumab Vedotin or Durvalumab and Enfortumab Vedotin in Patients With Muscle Invasive Bladder Cancer Ineligible to Cisplatin or Who Refuse Cisplatin
A Phase 3 study testing Durvalumab, Tremelimumab and Enfortumab Vedotin in people with Muscle Invasive Bladder Cancer, run by AstraZeneca at 196 sites in 25 countries.
Trial summary
A global phase 3, multicenter, randomized, trial, to Determine the Efficacy and Safety of Durvalumab in combination with Tremelimumab and Enfortumab Vedotin or Durvalumab in combination with Enfortumab Vedotin for Perioperative Treatment in Patients Ineligible for Cisplatin or who refuse Cisplatin based chemotherapy… Read more about this study
- Who is it for?
- Ages 18 to 130 years
- Conditions the study is for
- Muscle Invasive Bladder Cancer
- What is being tested?
- Durvalumab, Tremelimumab and Enfortumab Vedotin
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 712 participants
- Where
- 196 sitesin 25 countries
- Study dates
- 5 Aug 2021to 8 Sep 2028
- Phase
- Phase 3
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 130 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Histologically or cytologically documented muscle-invasive UC of the bladder.
- Participants with transitional cell and mixed transitional/non-transitional cell histologies;
- Participants with MIBC clinical tumor (T) stage T2-T4aN0/1M0 or UC of the bladder with clinical state T1N1M0 (participants with T1 stage are allowed only with N1 disease)
- Participants should also have not received prior systemic chemotherapy or immunotherapy for the treatment of MIBC or bladder UC.
- Medically fit for cystectomy and able to receive neoadjuvant therapy;
- Patients who have not received prior systemic chemotherapy or immunotherapy for treatment of MIBC;
Show all 10Show fewer
- ECOG performance status of 0,1,2 at enrollment.
- Availability of tumor sample prior to study entry;
- Must have a life expectancy of at least 12 weeks at randomization.
- Cisplatin-ineligible, following criteria based on Galsky et al 2011 OR Refuse cisplatin based chemotherapy (must be documented in the medical records)
Who cannot join
- Evidence of lymph node (N2+) or metastatic TCC/UC disease at the time of screening.
- Active infection
- Uncontrolled intercurrent illness
- Prior exposure to immune-mediated therapy (with exclusion of Bacillus-Calmette Guerin [BCG]), including but not limited to other anti-CTLA-4, anti--PD-1, anti PD-L1, or anti-PD-L2 antibodies.
- Current or prior use of immunosuppressive medication within 14 days before the first dose of IPs.
Trial locations and contacts
196 sites in 25 countries.
196 sites in 25 countries
United States31 sites
Research Site
Austin, Texas, 78731
Research Site
Boston, Massachusetts, 02111
Research Site
Brighton, Michigan, 48114
Research Site
Brooklyn, New York, 11219
Research Site
Buffalo, New York, 14263
Research Site
Coeur d'Alene, Idaho, 83814
Research Site
Dallas, Texas, 75246
Research Site
Fort Myers, Florida, 33901
Research Site
Fort Worth, Texas, 76104
Research Site
Hershey, Pennsylvania, 17033
Research Site
Houston, Texas, 77030
Research Site
Indianapolis, Indiana, 46250
Research Site
Iowa City, Iowa, 52242
Research Site
Irving, Texas, 75063
Research Site
Jackson, Mississippi, 39213
Research Site
Knoxville, Tennessee, 37932
Research Site
Las Vegas, Nevada, 89102
Research Site
Louisville, Kentucky, 40207
Research Site
Maywood, Illinois, 60153
Research Site
New Haven, Connecticut, 06510
Research Site
New York, New York, 10040
Research Site
Norfolk, Virginia, 23502
Research Site
Orange, California, 92868
Research Site
Pittsburgh, Pennsylvania, 15212
Research Site
Portland, Oregon, 97239
Research Site
Saddle Brook, New Jersey, 07663
Research Site
Santa Monica, California, 90404
Research Site
Scarborough, Maine, 04074
Research Site
Spokane, Washington, 99208
Research Site
Syracuse, New York, 13210
Research Site
Washington D.C., District of Columbia, 20010
Japan20 sites
Research Site
Bunkyō City, 113-8431
Research Site
Fukuoka, 811-1395
Research Site
Hamamatsu, 431-3192
Research Site
Ichikawa-shi, 272-8516
Research Site
Kanazawa, 920-8641
Research Site
Kashihara-shi, 634-8522
Research Site
Kawasaki-shi, 216-8511
Research Site
Kita-gun, 761-0793
Research Site
Kobe, 650-0017
Research Site
Kumamoto, 860-0008
Research Site
Matsuyama, 791-0288
Research Site
Miyazaki, 889-1692
Research Site
Niigata, 951-8566
Research Site
Okayama, 700-8558
Research Site
Osaka, 541-8567
Research Site
Osaka, 545-8586
Research Site
Osakasayama-shi, 589-8511
Research Site
Toyama, 930-0194
Research Site
Tsukuba, 305-8576
Research Site
Yokohama, 241-8515
France15 sites
Research Site
Amiens, 80090
Research Site
Bayonne, 64100
Research Site
Clermont-Ferrand, 63011
Research Site
Lille, 59000
Research Site
Lyon, 69008
Research Site
Marseille, 13273
Research Site
Marseille, 13385
Research Site
Montpellier, 34070
Research Site
Nice, 06189
Research Site
Pierre-Bénite, 69495
Research Site
Quint-Fonsegrives, 31130
Research Site
Saint-Priez En Jarez, 42270
Research Site
Strasbourg, 67091
Research Site
Suresnes, 92151
Research Site
Vandœuvre-lès-Nancy, 54519
Germany15 sites
Research Site
Bielefeld, 33611
Research Site
Bochum, 44791
Research Site
Cologne, 50937
Research Site
Düsseldorf, 40225
Research Site
Giessen, 35392
Research Site
Hanover, 30625
Research Site
Herne, 44625
Research Site
Magdeburg, 39120
Research Site
Mainz, 55131
Research Site
Mannheim, 68167
Research Site
München, 81377
Research Site
Münster, 48149
Research Site
Regensburg, 93053
Research Site
Reutlingen, 72766
Research Site
Ulm, 89075
Italy14 sites
Research Site
Bari, 70124
Research Site
Florence, 50134
Research Site
Meldola, 47014
Research Site
Milan, 20132
Research Site
Milan, 20141
Research Site
Padova, 35128
Research Site
Pozzuoli, 80078
Research Site
Reggio Emilia, 42100
Research Site
Roma, 00128
Research Site
Roma, 00137
Research Site
Roma, 00144
Research Site
Terni, 05100
Research Site
Tricase, 73039
Research Site
Verona, 37124
Brazil11 sites
Research Site
Barretos, 14784-400
Research Site
Curitiba, 81520-060
Research Site
Fortaleza, 60135-237
Research Site
Porto Alegre, 90035-001
Research Site
Porto Alegre, 90035-003
Research Site
Rio de Janeiro, 22250-905
Research Site
Santa Maria, 97015-450
Research Site
Săo Paulo, 03162-065
Research Site
São Paulo, 01246-000
Research Site
São Paulo, 01323-903
Research Site
Uberlândia, 38408-150
Spain11 sites
Research Site
Barcelona, 08035
Research Site
Barcelona, 08036
Research Site
Barcelona, 08041
Research Site
Barcelona, 08208
Research Site
L'Hospitalet de Llobregat, 08907
Research Site
Las Palmas de Gran Canaria, 35016
Research Site
Madrid, 28033
Research Site
Madrid, 28040
Research Site
Madrid, 28046
Research Site
Pamplona, 31008
Research Site
Seville, 41009
Turkey (Türkiye)10 sites
Research Site
Adana, 01060
Research Site
Ankara, 06560
Research Site
Ankara, 06620
Research Site
Ankara, 5000
Research Site
Ankara
Research Site
Antalya, 07025
Research Site
Cordaleo, 35575
Research Site
Edirne, 22030
Research Site
Istanbul, 32098
Research Site
Istanbul, 34722
South Korea9 sites
Research Site
Busan, 47392
Research Site
Goyang-si, 10408
Research Site
Incheon, 405-760
Research Site
Seongnam-si, 13620
Research Site
Seoul, 02841
Research Site
Seoul, 03080
Research Site
Seoul, 06351
Research Site
Seoul, 06591
Research Site
Seoul, 07985
Portugal8 sites
Research Site
Braga, 4710
Research Site
Coimbra, 3000-075
Research Site
Faro, 8000-386
Research Site
Lisbon, 1169-050
Research Site
Lisbon, 1350-352
Research Site
Lisbon, 1500-458
Research Site
Lisbon, 1500-650
Research Site
Lisbon, 1649-035
Netherlands6 sites
Research Site
Arnhem, 6815 AD
Research Site
Breda, 4818 CK
Research Site
Groningen, 9713 GZ
Research Site
Hoofddorp, 2134 TM
Research Site
Leiden, 2333 ZA
Research Site
Utrecht, 3508 GA
Argentina5 sites
Research Site
Buenos Aires, C1431FWO
Research Site
CABA, C1426ANZ
Research Site
Ciudad de Buenos Aires, C1280AEB
Research Site
Ciudad de Buenos Aires, C1419AHL
Research Site
Pergamino, B2700CPM
Austria5 sites
Research Site
Graz, 8036
Research Site
Krems, 3500
Research Site
Linz, 4020
Research Site
Vienna, 1020
Research Site
Wiener Neustadt, 2700
Israel5 sites
Research Site
Hadera, 38100
Research Site
Haifa, 31096
Research Site
Jerusalem, 9103102
Research Site
Jerusalem, 9112001
Research Site
Tel Aviv, 64239
Canada4 sites
Research Site
Abbotsford British Columbia, British Columbia, V2S 3N5
Research Site
Québec, Quebec, G1R 2J6
Research Site
Sherbrooke, Quebec, J1H 5N4
Research Site
Toronto, Ontario, M4N 3M5
Poland4 sites
Research Site
Gdansk, 80-214
Research Site
Nowa Sól, 67-106
Research Site
Skórzewo, 60-185
Research Site
Warsaw, 02-781
Taiwan4 sites
Research Site
Taichung, 40447
Research Site
Taichung, 40705
Research Site
Tainan, 70403
Research Site
Tainan, 710
Vietnam4 sites
Research Site
Hà Nội, 100000
Research Site
Hanoi, 100000
Research Site
Ho Chi Minh City, 700000
Research Site
Huế, 530000
Greece3 sites
Research Site
Athens, 11528
Research Site
Athens, 12462
Research Site
Maroussi, Athens, 15125
Thailand3 sites
Research Site
Bangkok, 10330
Research Site
Dusit, 10300
Research Site
Songkhla, 90110
United Kingdom2 sites
Research Site
London, EC1A 7BE
Research Site
London, NW1 2PG
About this study
Official title: A Phase III Randomized, Open-Label, Multicenter Study to Determine the Efficacy and Safety of Durvalumab in Combination With Tremelimumab and Enfortumab Vedotin or Durvalumab in Combination With Enfortumab Vedotin for Perioperative Treatment in Patients Ineligible for Cisplatin or Who Refuse Cisplatin Undergoing Radical Cystectomy for Muscle Invasive Bladder Cancer (VOLGA)
A global phase 3, multicenter, randomized, trial, to Determine the Efficacy and Safety of Durvalumab in combination with Tremelimumab and Enfortumab Vedotin or Durvalumab in combination with Enfortumab Vedotin for Perioperative Treatment in Patients Ineligible for Cisplatin or who refuse Cisplatin based chemotherapy Undergoing Radical Cystectomy for Muscle Invasive Bladder Cancer.
The goal of the study is to explore the triplet combination of Durvalumab, Tremelimumab and Enfortumab Vedotin or the duplet combination of Durvalumab and Enfortumab vedotin in terms of efficacy and safety compared to the current Standard Of Care (SOC).
Read more
VOLGA trial consists of two parts: Safety Run-In and Main Study. In total the study aims to enroll approximately 677 patients, who will receive triplet combination, duplet combination or currently approved SOC in the main study. In the main part of the trial there is two out of three chances of being on a treatment arm and the treatment is assigned at random by a computer system.
In this trial patients in the two treatment arms will receive either 3 cycles of neoadjuvant Durvalumab + Enfortumab Vedotin and 2 cycles of Tremelimumab or Durvalumab + Enfortumab vedotin and after surgery both treatment arms will receive either adjuvant Durvalumab or adjuvant Durvalumab and 1 cycle of Tremelimumab.
Read the detailed description
Not provided
- Conditions
- Muscle Invasive Bladder Cancer
- Being tested
- Durvalumab, Tremelimumab, Enfortumab Vedotin, Radical Cystectomy
- Keywords
- Bladder Cancer, Immunotherapy, PD-L1, Durvalumab (MEDI4736), Tremelimumab, Enfortumab Vedotin (PADCEV)
- Medical subject headings
- Urinary Bladder Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DurvalumabDrug
Also called IMFINZI, MEDI4736
Anti- PD-L1 Antibody
TremelimumabDrug
Human IgG2 mAb
Enfortumab VedotinDrug
Also called PADCEV
Nectin-4-directed antibody and microtubule inhibitor conjugate
Radical CystectomyProcedure or surgery
For cisplatin-ineligible or cisplatin-refusal patients
| Study group | Role | What they receive |
|---|---|---|
| Durvalumab + Tremelimumab + Enfortumab Vedotin | Experimental | Participants will receive 3 preoperative 21-day cycles of Durvalumab + Enfortumab Vedotin and 2 cycles of Tremelimumab, followed by radical cystectomy, followed by 1 cycle of postoperative Tremelimumab and 9 cycles of Durvalumab. Each postoperative cycle is 28 days. Receives: Drug: Durvalumab; Drug: Tremelimumab; Drug: Enfortumab Vedotin; Procedure: Radical Cystectomy |
| Durvalumab + Enfortumab vedotin | Experimental | Participants will receive 3 preoperative 21-day cycles of Durvalumab + Enfortumab Vedotin, followed by radical cystectomy, followed by 9 cycles of Durvalumab. Each postoperative cycle is 28 days. Receives: Drug: Durvalumab; Drug: Enfortumab Vedotin; Procedure: Radical Cystectomy |
| Cystectomy with or without approved Adjuvant Therapy. | Active comparator | Participants may receive SoC (nivolumab approved as adjuvant treatment for MIBC based on high risk criteria) per approved label in the country OR Participants receive standard of care surgery (radical cystectomy) alone. Receives: Procedure: Radical Cystectomy |
What is being measured
The primary outcome is the main question the study is designed to answer.
To assess the safety and tolerability as evaluated by adverse events occurring throughout the study (Safety Run-In part)
Frequency of Adverse Events.
Measured: At completion of study treatment by the last patient and at 3 months.
To assess the safety and tolerability of durvalumab + tremelimumab + EV in participants with MIBC who are ineligible for cisplatin as assessed by vital signs (blood pressure in mmHg) (Safety Run-In part)
Measured: Up to 84 months
To assess the safety and tolerability of durvalumab + tremelimumab + EV in participants with MIBC who are ineligible for cisplatin as assessed by vital signs (pulse rate) in beats per minute (Safety Run-In part)
Measured: Up to 84 months
To assess the safety and tolerability of durvalumab + tremelimumab + EV in participants with MIBC who are ineligible for cisplatin as assessed by vital signs (respiration rate) in breaths per minute (Safety Run-In part)
Measured: Up to 84 months
To assess the safety and tolerability of durvalumab + tremelimumab + EV in participants with MIBC who are ineligible for cisplatin as assessed by vital signs (temperature) in degrees Celsius (Safety Run-In part)
Measured: Up to 84 months
To assess the safety and tolerability of durvalumab + tremelimumab + EV in participants with MIBC who are ineligible for cisplatin as assessed by abnormality in clinical chemistry by liver function (Safety Run-In part)
Clinical chemistry will be assessed by liver function assessment (ALT, AST, albumin, total bilirubin measured in units per dL)
Measured: Up to 84 months
Safety and tolerability of durvalumab + tremelimumab + EV in participants with MIBC who are ineligible for cisplatin or who refuse cisplatin as assessed by abnormality in clinical chemistry by kidney function (Safety Run-In part)
Clinical chemistry will be assessed by kidney function assessment in mg/dL
Measured: Up to 84 months
To assess the safety and tolerability of durvalumab + tremelimumab + EV in participants with MIBC who are ineligible for cisplatin as assessed by abnormality in clinical chemistry by thyroid function (Safety Run-In part)
Clinical chemistry will be assessed by thyroid function assessment in units per mL.
Measured: Up to 84 months
To assess the safety and tolerability of durvalumab + tremelimumab + EV in participants with MIBC who are ineligible for cisplatin as assessed by abnormality in haematology (Safety Run-In part)
Hematology will be assessed by white cell count, platelet count, absolute neutrophil count and absolute lymphocyte count.
Measured: Up to 84 months
To assess the safety and tolerability of durvalumab + tremelimumab + EV in participants with MIBC who are ineligible for cisplatin as as assessed by ECG (pulse rate) (Safety Run-In part)
Measured: Up to 84 months
Changes in WHO/ECOG performance status (Safety Run-In part)
Eastern Cooperative Oncology Group (ECOG) performance status scale range 0 to 5, where 0 is fully active, able to carry on all pre disease performance without restriction - best outcome and 5 -death - worst outcome.
Measured: Up to 84 months
Compare efficacy of durvalumab + tremelimumab + EV (Arm 1) relative to cystectomy (Arm 3) and durvalumab + EV (Arm 2) relative to cystectomy (Arm 3) on EFS (Main Study)
Event-free survival (EFS;) is defined as the time from randomization to the first occurrence of any of the following events: recurrence of disease post-radical cystectomy, the first documented progression in participants who did not receive radical cystectomy, failure to undergo radical cystectomy in participants with residual disease, or death due to any cause, up to 3 years.
Measured: Up to 3 years
Secondary outcomes (13)
1. To evaluate the efficacy of durvalumab + tremelimumab + EV on pCR rate (Safety Run-in part)
Pathologic complete response (pCR) rate is defined as the number of participants whose pathological staging was T0N0M0 as assessed per local pathology and central independent review using specimens obtained via cystectomy, at 3 years.
Measured: 3 years
2. To evaluate the efficacy of durvalumab + tremelimumab + EV on EFS (Safety Run-in part)
Event-free survival (EFS;) is defined as the time from randomization to the first occurrence of any of the following events: recurrence of disease post-radical cystectomy, the first documented progression in participants who did not receive radical cystectomy, failure to undergo radical cystectomy in participants with residual disease, or death due to any cause, up to 3 years.
Measured: 3 years
3. Pathologic complete response (pCR) rates at time of cystectomy in Arm1 vs Arm3 and Arm 2 vs Arm 3 (Main Study part)
Pathologic complete response (pCR) rate is defined as the number of participants whose pathological staging was T0N0M0 as assessed per local pathological review using specimens obtained via cystectomy, at 3 years.
Measured: 3 years
4. Overall survival (Safety Run-in and Main Study part)
Overall Survival is defined as length of time from randomization until the date of death due to any cause, whichever came first, assessed up to 5 years.
Measured: Up to 5 years
5. EFS at 24 months (EFS24) (Safety Run-in and Main Study part)
EFS24 is defined as proportion of participants alive and event-free at 24 months
Measured: Up to 24 months
6. Overall survival rate at 5 years (Safety Run-in and Main Study part)
The proportion of participants alive at 5 years (OS5) is defined as the Kaplan-Meier estimate of OS at 5 years after randomization
Measured: At 5 years
7. Disease-free survival (DFS) (Safety Run-in and Main Study part)
DFS is defined as time from radical cystectomy to recurrence or death, whichever came first, assessed up to 5 years.
Measured: Up to first recurrence of disease or death up to 5 years
8. Pathologic downstaging (pDS) rate-to < pT2 (Safety Run-in and Main Study part)
pDS rate is defined as the rate of downstaging to < pT2, including pT0, pTis, pTa, pT1, and N0
Measured: 3 years
9. Disease-specific survival (DSS) (Safety Run-in and Main Study part)
DSS is defined as time from randomization until death due to bladder cancer, assessed up to 5 years.
Measured: from randomization until death due to bladder cancer up to 5 year.
10. EORTC QLQ-C30 European Organisation for Research and Treatment of Cancer 30-item Core Quality of Life Questionnaire) (Safety Run-in and Main Study part)
Measured: from baseline and time to definitive clinically, assessed up to 5 years
11. Immunogenicity of durvalumab when used in combination with Tremelimumab as measured by presence of antidrug antibodies (ADA) (Safety Run-in and Main Study part)
Measured: At 3 months after last dose of durvalumab and tremelimumab
12. Time to maximum observed serum concentration (tmax) of durvalumab and tremelimumab (Safety Run-in and Main Study part)
Measured: At 3 months after last dose of durvalumab and tremelimumab
13. Metastasis-free survival (MFS) (Safety Run-in and Main Study part)
MFS is defined as the time from date of randomization until the first recognition of distant metastases or death, whichever occurs first, up to approximately 48 months.
Measured: From randomization until the first recognition of distant metastases or death, up to approximately 48 months.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Jul 2021
- Study start5 Aug 2021
- Primary completion2 Mar 2026
- Study completion8 Sep 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Muscle Invasive Bladder CancerStudies of the same condition, open and under way.
- More trials run by AstraZenecaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Parallel
- Masking
- None (open label)
- Enrolment
- 712 participants (actual)
Sponsor and investigators
- Lead sponsor
- AstraZeneca
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04960709
- Sponsor's protocol ID
- D910PC00001
- Other IDs
- 2020-005452-38
- Acronym
- VOLGA
- Status last verified
- May 2026
- First submitted
- 17 Jun 2021
- Last updated
- 4 Jun 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All requests will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
Publications
Powles T, Grande E, Simone G, Gomez de Liano A, Maruzzo M, Velho PI, Kikuchi E, Vu TQ, Popovic L, Cil T, Gravis G, Radkowski R, Hernandez LRN, Cutuli HJ, Bamias A, Bauernhofer T, Pavic M, Choi YJ, Chang CH, Kitamura H, Rosenberg JE, Rowbottom J, Ho S, Gupta A, Drakaki A; VOLGA Investigators. Durvalumab, Tremelimumab, and Enfortumab Vedotin in Muscle-Invasive Bladder Cancer. N Engl J Med. 2026 Oct 24. doi: 10.1056/NEJMoa2608323. Online ahead of print.
PubMed 42929692
Study at a glance
From the registry record, last updated by the sponsor on 4 Jun 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase III Randomized, Open-Label, Multicenter Study to Determine the Efficacy and Safety of Durvalumab in Combination With Tremelimumab and Enfortumab Vedotin or Durvalumab in Combination With Enfortumab Vedotin for Perioperative Treatment in Patients Ineligible for Cisplatin or Who Refuse Cisplatin Undergoing Radical Cystectomy for Muscle Invasive Bladder Cancer (VOLGA)
- ClinicalTrials.gov ID
- NCT04960709
- Acronym / sponsor ID
- VOLGA / D910PC00001
- Conditions
- Muscle Invasive Bladder Cancer
- Keywords
- Bladder Cancer, Immunotherapy, PD-L1, Durvalumab (MEDI4736), Tremelimumab, Enfortumab Vedotin (PADCEV)
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 712 participants (actual)
- Lead sponsor
- AstraZenecaIndustry (pharma, biotech, devices)
- Study start
- 5 Aug 2021 (actual)
- Primary completion
- 2 Mar 2026 (actual)
- Study completion
- 8 Sep 2028 (estimated)
- First posted
- 14 Jul 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
A global phase 3, multicenter, randomized, trial, to Determine the Efficacy and Safety of Durvalumab in combination with Tremelimumab and Enfortumab Vedotin or Durvalumab in combination with Enfortumab Vedotin for Perioperative Treatment in Patients Ineligible for Cisplatin or who refuse Cisplatin based chemotherapy Undergoing Radical Cystectomy for Muscle Invasive Bladder Cancer.
The goal of the study is to explore the triplet combination of Durvalumab, Tremelimumab and Enfortumab Vedotin or the duplet combination of Durvalumab and Enfortumab vedotin in terms of efficacy and safety compared to the current Standard Of Care (SOC).
VOLGA trial consists of two parts: Safety Run-In and Main Study. In total the study aims to enroll approximately 677 patients, who will receive triplet combination, duplet combination or currently approved SOC in the main study. In the main part of the trial there is two out of three chances of being on a treatment arm and the treatment is assigned at random by a computer system.
In this trial patients in the two treatment arms will receive either 3 cycles of neoadjuvant Durvalumab + Enfortumab Vedotin and 2 cycles of Tremelimumab or Durvalumab + Enfortumab vedotin and after surgery both treatment arms will receive either adjuvant Durvalumab or adjuvant Durvalumab and 1 cycle of Tremelimumab.
Detailed description
Not provided
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
- Model description
- Parallel
| Arm | Type | Receives |
|---|---|---|
| Durvalumab + Tremelimumab + Enfortumab Vedotin | Experimental | Drug: Durvalumab, Drug: Tremelimumab, Drug: Enfortumab Vedotin, Procedure: Radical CystectomyParticipants will receive 3 preoperative 21-day cycles of Durvalumab + Enfortumab Vedotin and 2 cycles of Tremelimumab, followed by radical cystectomy, followed by 1 cycle of postoperative Tremelimumab and 9 cycles of Durvalumab. Each postoperative cycle is 28 days. |
| Durvalumab + Enfortumab vedotin | Experimental | Drug: Durvalumab, Drug: Enfortumab Vedotin, Procedure: Radical CystectomyParticipants will receive 3 preoperative 21-day cycles of Durvalumab + Enfortumab Vedotin, followed by radical cystectomy, followed by 9 cycles of Durvalumab. Each postoperative cycle is 28 days. |
| Cystectomy with or without approved Adjuvant Therapy. | Active comparator | Procedure: Radical CystectomyParticipants may receive SoC (nivolumab approved as adjuvant treatment for MIBC based on high risk criteria) per approved label in the country OR Participants receive standard of care surgery (radical cystectomy) alone. |
Who may qualify
- Ages
- 18 to 130 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- Histologically or cytologically documented muscle-invasive UC of the bladder.
- Participants with transitional cell and mixed transitional/non-transitional cell histologies;
- Participants with MIBC clinical tumor (T) stage T2-T4aN0/1M0 or UC of the bladder with clinical state T1N1M0 (participants with T1 stage are allowed only with N1 disease)
- Participants should also have not received prior systemic chemotherapy or immunotherapy for the treatment of MIBC or bladder UC.
- Medically fit for cystectomy and able to receive neoadjuvant therapy;
Key exclusion criteria (5 listed)
- Evidence of lymph node (N2+) or metastatic TCC/UC disease at the time of screening.
- Active infection
- Uncontrolled intercurrent illness
- Prior exposure to immune-mediated therapy (with exclusion of Bacillus-Calmette Guerin [BCG]), including but not limited to other anti-CTLA-4, anti--PD-1, anti PD-L1, or anti-PD-L2 antibodies.
- Current or prior use of immunosuppressive medication within 14 days before the first dose of IPs.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| DurvalumabAlso: IMFINZI, MEDI4736Anti- PD-L1 Antibody | Drug | Durvalumab + Enfortumab vedotin, Durvalumab + Tremelimumab + Enfortumab Vedotin |
| TremelimumabHuman IgG2 mAb | Drug | Durvalumab + Tremelimumab + Enfortumab Vedotin |
| Enfortumab VedotinAlso: PADCEVNectin-4-directed antibody and microtubule inhibitor conjugate | Drug | Durvalumab + Enfortumab vedotin, Durvalumab + Tremelimumab + Enfortumab Vedotin |
| Radical CystectomyFor cisplatin-ineligible or cisplatin-refusal patients | Procedure or surgery | Cystectomy with or without approved Adjuvant Therapy., Durvalumab + Enfortumab vedotin, Durvalumab + Tremelimumab + Enfortumab Vedotin |
Primary outcome
To assess the safety and tolerability as evaluated by adverse events occurring throughout the study (Safety Run-In part)
Time frame: At completion of study treatment by the last patient and at 3 months.
Frequency of Adverse Events.
To assess the safety and tolerability of durvalumab + tremelimumab + EV in participants with MIBC who are ineligible for cisplatin as assessed by vital signs (blood pressure in mmHg) (Safety Run-In part)
Time frame: Up to 84 months
To assess the safety and tolerability of durvalumab + tremelimumab + EV in participants with MIBC who are ineligible for cisplatin as assessed by vital signs (pulse rate) in beats per minute (Safety Run-In part)
Time frame: Up to 84 months
To assess the safety and tolerability of durvalumab + tremelimumab + EV in participants with MIBC who are ineligible for cisplatin as assessed by vital signs (respiration rate) in breaths per minute (Safety Run-In part)
Time frame: Up to 84 months
To assess the safety and tolerability of durvalumab + tremelimumab + EV in participants with MIBC who are ineligible for cisplatin as assessed by vital signs (temperature) in degrees Celsius (Safety Run-In part)
Time frame: Up to 84 months
To assess the safety and tolerability of durvalumab + tremelimumab + EV in participants with MIBC who are ineligible for cisplatin as assessed by abnormality in clinical chemistry by liver function (Safety Run-In part)
Time frame: Up to 84 months
Clinical chemistry will be assessed by liver function assessment (ALT, AST, albumin, total bilirubin measured in units per dL)
Safety and tolerability of durvalumab + tremelimumab + EV in participants with MIBC who are ineligible for cisplatin or who refuse cisplatin as assessed by abnormality in clinical chemistry by kidney function (Safety Run-In part)
Time frame: Up to 84 months
Clinical chemistry will be assessed by kidney function assessment in mg/dL
To assess the safety and tolerability of durvalumab + tremelimumab + EV in participants with MIBC who are ineligible for cisplatin as assessed by abnormality in clinical chemistry by thyroid function (Safety Run-In part)
Time frame: Up to 84 months
Clinical chemistry will be assessed by thyroid function assessment in units per mL.
To assess the safety and tolerability of durvalumab + tremelimumab + EV in participants with MIBC who are ineligible for cisplatin as assessed by abnormality in haematology (Safety Run-In part)
Time frame: Up to 84 months
Hematology will be assessed by white cell count, platelet count, absolute neutrophil count and absolute lymphocyte count.
To assess the safety and tolerability of durvalumab + tremelimumab + EV in participants with MIBC who are ineligible for cisplatin as as assessed by ECG (pulse rate) (Safety Run-In part)
Time frame: Up to 84 months
Changes in WHO/ECOG performance status (Safety Run-In part)
Time frame: Up to 84 months
Eastern Cooperative Oncology Group (ECOG) performance status scale range 0 to 5, where 0 is fully active, able to carry on all pre disease performance without restriction - best outcome and 5 -death - worst outcome.
Compare efficacy of durvalumab + tremelimumab + EV (Arm 1) relative to cystectomy (Arm 3) and durvalumab + EV (Arm 2) relative to cystectomy (Arm 3) on EFS (Main Study)
Time frame: Up to 3 years
Event-free survival (EFS;) is defined as the time from randomization to the first occurrence of any of the following events: recurrence of disease post-radical cystectomy, the first documented progression in participants who did not receive radical cystectomy, failure to undergo radical cystectomy in participants with residual disease, or death due to any cause, up to 3 years.
13 secondary outcomes
1. To evaluate the efficacy of durvalumab + tremelimumab + EV on pCR rate (Safety Run-in part)
Time frame: 3 years
2. To evaluate the efficacy of durvalumab + tremelimumab + EV on EFS (Safety Run-in part)
Time frame: 3 years
3. Pathologic complete response (pCR) rates at time of cystectomy in Arm1 vs Arm3 and Arm 2 vs Arm 3 (Main Study part)
Time frame: 3 years
4. Overall survival (Safety Run-in and Main Study part)
Time frame: Up to 5 years
5. EFS at 24 months (EFS24) (Safety Run-in and Main Study part)
Time frame: Up to 24 months
6. Overall survival rate at 5 years (Safety Run-in and Main Study part)
Time frame: At 5 years
7. Disease-free survival (DFS) (Safety Run-in and Main Study part)
Time frame: Up to first recurrence of disease or death up to 5 years
8. Pathologic downstaging (pDS) rate-to < pT2 (Safety Run-in and Main Study part)
Time frame: 3 years
9. Disease-specific survival (DSS) (Safety Run-in and Main Study part)
Time frame: from randomization until death due to bladder cancer up to 5 year.
10. EORTC QLQ-C30 European Organisation for Research and Treatment of Cancer 30-item Core Quality of Life Questionnaire) (Safety Run-in and Main Study part)
Time frame: from baseline and time to definitive clinically, assessed up to 5 years
11. Immunogenicity of durvalumab when used in combination with Tremelimumab as measured by presence of antidrug antibodies (ADA) (Safety Run-in and Main Study part)
Time frame: At 3 months after last dose of durvalumab and tremelimumab
12. Time to maximum observed serum concentration (tmax) of durvalumab and tremelimumab (Safety Run-in and Main Study part)
Time frame: At 3 months after last dose of durvalumab and tremelimumab
13. Metastasis-free survival (MFS) (Safety Run-in and Main Study part)
Time frame: From randomization until the first recognition of distant metastases or death, up to approximately 48 months.
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Jun 2026.
- Derived from this study: PubMed 42929692Powles T, Grande E, Simone G, Gomez de Liano A, Maruzzo M, Velho PI, Kikuchi E, Vu TQ, Popovic L, Cil T, Gravis G, Radkowski R, Hernandez LRN, Cutuli HJ, Bamias A, Bauernhofer T, Pavic M, Choi YJ, Chang CH, Kitamura H, Rosenberg JE, Rowbottom J, Ho S, Gupta A, Drakaki A; VOLGA Investigators. Durvalumab, Tremelimumab, and Enfortumab Vedotin in Muscle-Invasive Bladder Cancer. N Engl J Med. 2026 Oct 24. doi: 10.1056/NEJMoa2608323. Online ahead of print.
- Individual participant dataSharing planned: Yes. Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All requests will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
196 sites in 25 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Durvalumab, Tremelimumab and Enfortumab Vedotin in people with Muscle Invasive Bladder Cancer, run by AstraZeneca at 196 sites in 25 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 4 Jun 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 196 sites in United States, Japan, France, Germany, Italy and 20 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
To assess the safety and tolerability as evaluated by adverse events occurring throughout the study (Safety Run-In part) (time frame: At completion of study treatment by the last patient and at 3 months.). The study lists 12 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04960709, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Jun 2026.