The phase 1b portion of the DURANCE trial (NCT04106115) evaluated the efficacy and safety of adding durvalumab (Imfinzi) to S-488210/S-488211 vaccine therapy in patients with Bacillus Calmette-Guérin (BCG)–unresponsive non–muscle-invasive bladder cancer (NMIBC). As of October 21, 2024, the 3- and 6-month disease-free survival (DFS) rates were 71% and 57%, respectively. Eight patients remained disease-free at the 24-week assessment post-treatment.
Gianmarco Leone, a PhD student and clinical research fellow at University College London, highlighted the treatment's tolerability and safety profile, which resembles that of checkpoint inhibitor monotherapy with additional injection site reactions. NMIBC accounts for 75% to 80% of new bladder cancer diagnoses, with standard treatment involving transurethral resection of bladder tumor plus BCG. However, 40% to 50% of patients experience disease recurrence, underscoring the need for effective second-line therapies.
The DURANCE trial enrolled patients over 18 with recurrent, high-risk NMIBC unresponsive or intolerant to prior BCG therapy, excluding those previously treated with immune checkpoint inhibitors. The treatment regimen included weekly vaccine administration for the first 6 weeks, followed by biweekly doses, alongside monthly durvalumab infusions. Patients underwent regular cystoscopies, field biopsies, and CT scans to monitor treatment efficacy and safety.
Adverse effects were manageable, with hypertension and injection site reactions being the most common. Serious adverse events were rare and not treatment-related. The trial's ongoing phase 2 aims to further assess the 1-year DFS rate, overall survival, and quality of life, alongside biomarker analyses to better understand the treatment's mechanism and efficacy.
This research represents a significant step forward in addressing the unmet need for effective treatments in BCG-unresponsive NMIBC, offering hope for improved outcomes in this challenging patient population.
