A New Therapeutic Option for BCG-Unresponsive Bladder Cancer

Patients with high-grade T1 or carcinoma in situ (CIS) bladder cancer who are unresponsive to treatment with intravesical bacillus Calmette–Guérin (BCG) have limited management options.

Now, investigators have conducted an industry-sponsored, multicenter, three-cohort, open-label trial to determine if intravesical nogapendekin alfa inbakicept (NAI) — an immune-cell–

activating interleukin-15 superagonist — can act synergistically with BCG in patients with BCG-unresponsive, non–muscle-invasive bladder cancer (NMIBC).

Patients in the three cohorts were treated for 6 weeks with the following results:

• Cohort A (84 patients), with BCG-unresponsive CIS with or without Ta/T1 papillary NMIBC, received NAI plus BCG. At median follow-up of 23.9 months, the complete response (CR) rate at 3 or 6 months (the primary endpoint) was 71%.
• Cohort B (77 patients), with BCG-unresponsive high-grade papillary Ta/T1 NMIBC, also received NAI and BCG. At a median follow-up of 20.7 months, disease-free survival at 12 months (the primary endpoint) was 55%.
• Cohort C (10 patients), with BCG-unresponsive CIS with or without Ta/T1 papillary NMIBC, received NAI alone. At median follow-up of 7.9 months, the CR rate at 3 or 6 months (the primary endpoint) was only 20%.
• In cohorts A and B, NAI plus BCG was well-tolerated with typical BCG-associated adverse effects. The most frequent grade 3 events were hematuria (2%) and urinary tract infection (2%). Three grade 3 immune adverse events occurred; 1 patient died from myocardial infarction.