FDA approves AstraZeneca’s Imfinzi combined with BCG for high-risk non-muscle-invasive bladder cancer

AstraZeneca announced that the US FDA has approved Imfinzi (durvalumab) in combination with Bacillus Calmette-Guérin (BCG) induction and maintenance therapy for adult patients with BCG-naïve, high-risk non-muscle-invasive bladder cancer (NMIBC). The approval marks the first immunotherapy combination cleared in this early-stage setting and, according to AstraZeneca, the first new therapy approved for BCG-naïve high-risk NMIBC in more than 30 years.

The approval rests on results from the POTOMAC Phase III trial, a randomized, open-label, multi-centre study enrolling 1,018 patients across more than 120 centres in 12 countries. Patients were randomized 1:1:1 to receive durvalumab plus BCG induction and maintenance therapy, durvalumab plus BCG induction only, or BCG induction and maintenance therapy alone. The primary endpoint was disease-free survival (DFS), defined as time to first recurrence of high-risk disease, progression, or death from any cause.

With a median follow-up exceeding five years (60.7 months), adding one year of durvalumab to BCG induction and maintenance reduced the risk of high-risk disease recurrence, progression, or death by 32% compared to BCG alone (DFS hazard ratio 0.68; 95% CI 0.50–0.93; p=0.0154). Median DFS was not yet reached in either arm. The DFS benefit emerged within four months of treatment initiation and was sustained throughout follow-up. The safety profile was consistent with the known profiles of each agent individually, with no new safety signals identified, and the addition of durvalumab did not compromise patients’ ability to complete BCG therapy.

Durvalumab is a human monoclonal antibody that binds PD-L1, blocking its interaction with both PD-1 and CD80, thereby countering tumour-mediated immune evasion. The combination rationale pairs BCG’s established intravesical immunostimulatory activity with durvalumab’s systemic checkpoint inhibition, potentially generating a more durable anti-tumour immune response in a setting where BCG alone leaves a substantial proportion of patients vulnerable to recurrence.

Competitive context

The approval positions AstraZeneca ahead of Merck & Co., whose anti-PD-1 agent pembrolizumab is being evaluated alongside BCG in BCG-naïve high-risk NMIBC in the Phase III KEYNOTE-676 trial — a design closely mirroring POTOMAC. Pembrolizumab holds a separate FDA approval in BCG-unresponsive NMIBC, a later-line setting, but has not yet secured clearance in the BCG-naïve population. The competitive picture was further shaped by the negative Phase III ALBAN trial, in which Roche’s atezolizumab — another anti-PD-L1 antibody — failed to meet its primary DFS endpoint when combined with BCG in the same patient population, underscoring that efficacy in this combination approach is not a class effect.

The approval also extends Imfinzi’s footprint in bladder cancer beyond muscle-invasive disease, where it is already approved in cisplatin-eligible patients based on the NIAGARA Phase III trial. Regulatory submissions based on POTOMAC are under review in the EU, Japan, and several other countries.