Patients with non-muscle–invasive urothelial carcinoma of the bladder who do not respond to BCG have limited treatment options. N-803 is an immunostimulant protein fusion complex based on mutant IL-15 (IL-15RαFc), which promotes the proliferation and activation of natural killer cells (NK) and CD8+ T cells, but not regulatory T cells
Phase Ib data in BCG-naive patients with non-muscle-invasive urothelial carcinoma of the bladder show that intravesical administration of N-803 with BCG induced a complete response in all patients, with no recurrences during the 24-month duration of the trial.
Based on the above results, QUILT 3,032 (NCT03022825), a phase II/III, open-label, multicenter, three-cohort trial of intravesical BCG plus N-803, was started in patients with high-grade non-muscle-invasive urothelial bladder carcinoma and unresponsive to BCG. During the 2021 Genitourinary Cancers Symposium, the results of a provisional analysis of cohort A were released, which recruited patients with urothelial carcinoma in situ (CIS) of the bladder (with or without Ta or T1 disease), who did not respond to BCG treatment.
All treated individuals received N-803 plus intravesical BCG, consistent with the standard induction and maintenance treatment regimen. The primary outcome for cohort A was the complete response (CR) of CIS at any time.
Up to now (cutoff date: December 2020), 80 patients have enrolled in cohort A of this phase II/III trial. The analysis showed that the CR rate was 72% (N = 51/71). Among the patients who achieved CR, the probability of maintaining it for 12 months was 59%, with a median duration of CR of 19.2 months.
Adverse events related to low-grade treatment included dysuria, hematuria and polyuria (all 16%), urgency (14%) and bladder hyperactivity (8%). All other adverse events were observed in 6% of patients or less. A total of nine individuals experienced at least one serious adverse event, with a rate of 1%. To date, 10 of the 80 patients (12.5%) underwent cystectomy with no response to BCG.
The authors conclude that, considering the CR rate of 72%, N-803 reached its primary outcome with a 59% probability of patients maintaining CR for at least 12 months. With strong efficacy observed and a rate of serious adverse events of 1%, N-803 represents a new treatment option for CIS not responsive to BCG, with a favorable risk-benefit ratio, in view of a disease challenging in terms of therapy.