NCT04960709: VOLGA

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

Active, enrolled Phase 3 Last updated 14 April 2026

What this trial tests

Phase 3 trial testing Durvalumab in Muscle Invasive Bladder Cancer in 712 participants. Participants enrolled and being followed up; not accepting new ones.

Timeline

5 August 2021

Primary endpoint
30 April 2026

8 September 2028

Quick facts

Lead sponsor	AstraZeneca
Phase	Phase 3
Status	Active, enrolled
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	none
Primary purpose	treatment
Enrollment	712
Start date	5 August 2021
Primary completion	30 April 2026
Estimated completion	8 September 2028
Sites	202 locations across Hong Kong, Italy, Japan, Taiwan, Vietnam, Poland, South Korea, Netherlands

Drugs / interventions tested

• Durvalumab — full drug profile →
• Tremelimumab (TREMELIMUMAB) — full drug profile →
• Enfortumab Vedotin — full drug profile →
• Radical Cystectomy

Conditions studied

• Muscle Invasive Bladder Cancer — all drugs for Muscle Invasive Bladder Cancer →

Sponsor

AstraZeneca — full company profile →

Who can join

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

Sponsor's own description

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.

Publications & conference data

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

1. Antibodies to watch in 2023.
   Kaplon H, Crescioli S, Chenoweth A, Visweswaraiah J, et al · · 2023 · cited 204× · PMID 36472472 · DOI 10.1080/19420862.2022.2153410
2. The promise and challenges of combination therapies with antibody-drug conjugates in solid tumors.
   Wei Q, Li P, Yang T, Zhu J, et al · · 2024 · cited 102× · PMID 38178200 · DOI 10.1186/s13045-023-01509-2
3. Mechanisms of Resistance to Antibody-Drug Conjugates.
   Khoury R, Saleh K, Khalife N, Saleh M, et al · · 2023 · cited 100× · PMID 37298631 · DOI 10.3390/ijms24119674
4. Perioperative Chemoimmunotherapy With Durvalumab for Muscle-Invasive Urothelial Carcinoma: Primary Analysis of the Single-Arm Phase II Trial SAKK 06/17.
   Cathomas R, Rothschild SI, Hayoz S, Bubendorf L, et al · · 2023 · cited 33× · PMID 37590894 · DOI 10.1200/jco.23.00363
5. Antibody-Drug Conjugates in Urothelial Carcinoma: A New Therapeutic Opportunity Moves from Bench to Bedside.
   Ungaro A, Tucci M, Audisio A, Di Prima L, et al · · 2022 · cited 33× · PMID 35269424 · DOI 10.3390/cells11050803
6. The combination of immune checkpoint inhibitors and antibody-drug conjugates in the treatment of urogenital tumors: a review insights from phase 2 and 3 studies.
   Yu P, Zhu C, You X, Gu W, et al · · 2024 · cited 28× · PMID 38898003 · DOI 10.1038/s41419-024-06837-w
7. An update on antibody-drug conjugates in urothelial carcinoma: state of the art strategies and what comes next.
   D'Angelo A, Chapman R, Sirico M, Sobhani N, et al · · 2022 · cited 21× · PMID 35953604 · DOI 10.1007/s00280-022-04459-7
8. Current and Future Landscape of Perioperative Treatment for Muscle-Invasive Bladder Cancer.
   Esteban-Villarrubia J, Torres-Jiménez J, Bueno-Bravo C, García-Mondaray R, et al · · 2023 · cited 20× · PMID 36765525 · DOI 10.3390/cancers15030566