Muscle-Invasive Bladder Cancer (Cisplatin-Ineligible) — Perioperative Durvalumab + Neoadjuvant Enfortumab Vedotin ± Tremelimumab — AstraZeneca
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VOLGA (NCT04960709) is a Phase III, randomized, open-label, multi-centre global trial sponsored by AstraZeneca evaluating perioperative durvalumab (Imfinzi) with or without tremelimumab (Imjudo) in combination with neoadjuvant enfortumab vedotin (EV) versus radical cystectomy with or without approved adjuvant therapy in patients with muscle-invasive bladder cancer (MIBC) who are ineligible for or have declined cisplatin-based chemotherapy. The trial enrolled 695 patients across 182 centres in 25 countries and was designed with dual primary EFS endpoints for each experimental arm versus the standard-of-care comparator.
On 14 May 2026, AstraZeneca announced positive high-level results from a planned interim analysis: perioperative durvalumab + neoadjuvant EV (Arm 2) demonstrated statistically significant and clinically meaningful improvements in both event-free survival and overall survival versus standard of care. The triplet of durvalumab + tremelimumab + neoadjuvant EV (Arm 1) also met the EFS endpoint with statistical significance and showed a favourable trend for OS, though OS for the triplet was not statistically significant at this interim and will be reassessed at a subsequent analysis. Detailed data are expected at a forthcoming medical meeting.
Adults with muscle-invasive urothelial carcinoma of the bladder undergoing radical cystectomy who were ineligible for or had declined cisplatin-based chemotherapy.
Phase 3, randomised, open-label, multi-centre. 695 patients randomised 1:1:1 across 182 centres in 25 countries (Europe, North America, South America, Asia).
3 cycles Imfinzi + EV plus 2 cycles Imjudo (neoadjuvant) → radical cystectomy → 9 cycles Imfinzi + 1 cycle Imjudo (adjuvant).
3 cycles Imfinzi + EV (neoadjuvant) → radical cystectomy → 9 cycles Imfinzi adjuvant monotherapy.
Radical cystectomy with or without approved adjuvant therapy (standard of care).
Dual primary endpoints of EFS for Arm 1 vs Arm 3 and Arm 2 vs Arm 3.
Overall survival (Arm 1 vs 3, Arm 2 vs 3), pathologic complete response, disease-free survival, pathologic downstaging.
AstraZeneca. NCT04960709 / EudraCT 2020-005452-38 / D910PC00001.
Both experimental arms met the EFS primary endpoint. Perioperative Imfinzi + neoadjuvant EV (Arm 2) demonstrated a statistically significant and clinically meaningful improvement in EFS versus standard of care. Perioperative Imfinzi + Imjudo + neoadjuvant EV (Arm 1) also demonstrated a statistically significant and clinically meaningful improvement in EFS versus standard of care. Specific hazard ratios and median EFS values have not been disclosed in the topline announcement and are expected at the next medical meeting.
Both experimental arms met EFSPerioperative Imfinzi + neoadjuvant EV (Arm 2) demonstrated a statistically significant and clinically meaningful improvement in overall survival versus standard of care. The triplet arm (Arm 1: Imfinzi + Imjudo + EV) showed a favourable trend for OS but did not reach statistical significance at this planned interim analysis; OS for the triplet will be formally reassessed at a subsequent analysis. Numeric hazard ratios and median OS values are not yet disclosed.
Arm 2 (doublet) met OS at interimPer AstraZeneca, the safety and tolerability of Imfinzi with or without Imjudo plus EV was consistent with the known safety profiles of the individual medicines, with no new safety signals identified at this interim analysis. Detailed safety data will be presented at a forthcoming medical meeting.
No new safety signalsIf validated by detailed data and regulatory review, VOLGA would establish a chemo-free perioperative immunotherapy + ADC backbone for cisplatin-ineligible MIBC — a population historically with limited curative-intent options beyond cystectomy. Doublet durvalumab + EV (Arm 2) emerged as the cleaner regimen at interim, achieving both EFS and OS. The triplet's incremental contribution beyond doublet remains an open question pending mature OS and detailed subgroup data. ⚠️ All findings remain investigational; the regimen is not FDA-approved in this setting.
Topline results: Arm 2 (Imfinzi + EV) hit stat-sig EFS and OS. Arm 1 (Imfinzi + Imjudo + EV) hit EFS with a favourable but non-significant OS trend at this interim. No new safety signals.
Original AstraZeneca corporate announcement. Quotes from Thomas Powles (international coordinating investigator) and Susan Galbraith (EVP, Oncology R&D). Positions VOLGA alongside NIAGARA and POTOMAC.
Correction summary clarifying the three-arm design and the differential results for Arm 1 vs Arm 2. Useful side-by-side framing of which arm hit which endpoint.
Investor-oriented context on MIBC epidemiology: ~25% of bladder cancer patients have muscle-invasive disease, and up to 50% of those are cisplatin-ineligible. Frames the commercial setting around radical cystectomy.
UK regulatory news service version of the AstraZeneca announcement, including the planned regulatory submission language: "shared with global regulatory authorities."
Authoritative protocol record: 3-arm design, ~677 patient target, dual primary EFS endpoints, key secondary endpoints (OS, pCR, DFS, pathologic downstaging), and full inclusion/exclusion criteria.
