Phase Ib trial of ALT-803, an IL-15 superagonist, plus Bacillus Calmette Guerin (BCG) for the treatment of patients with BCG-naïve non-muscle-invasive bladder cancer (NMIBC).

Abstract

470 Background: Novel agents are necessary to treat NMIBC to avoid recurrence and progression. This phase Ib clinical trial evaluated the safety and toleraibility of ALT-803, an IL-15 superagonist, plus BCG in patients with BCG-naïve NMIBC. Methods: This is a Phase Ib trial using the 3+3 design to evaluate intravesical ALT-803 plus BCG 50 mg in BCG-naïve NMIBC patients, who would normally be eligible for intravesical BCG alone. The initial dose of ALT-803 was 100 μg/instillation with 2 dose-escalations allowed (200 μg/instillation and 400 μg/instillation) if dose limiting toxicities (DLTs) were not evident. Patients received intravesical ALT-803 in conjunction with BCG weekly for 6 consecutive weeks (Induction Phase). Patients then had routine follow-up with cystoscopy and voided urinary cytology (VUC) every 3 months for 2 years equating to confirmatory response assessment. Negative cystoscopy, VUC and/or biopsy yielded a complete response (CR). When appropriate for high-risk patients, physicians and patients were encouraged to receive maintenance BCG alone as per common practice patterns. Results: No patient in 100 μg/instillation of ALT-803/BCG and 200 μg/instillation of ALT-803/BCG reported an AE. One patient in 400 μg/instillation/BCG cohort developed a urinary tract infection requiring delay of intravesical treatment by 1 week. No grade 3/4 toxicities were noted. All patients have completed therapy without DLTs. To date, 4 patients have 12 month follow-up and are CR. The remaining 5 patients have no evidence of disease. However, follow-ups are currently approximately 3 months. Corollary immune studies are still pending. Conclusions: Intravesical ALT-803 plus BCG was safe and tolerable in patients with BCG-naive NMIBC. Further evaluation in expansion cohorts in a phase II trial is currently underway. Clinical trial information: NCT02138734.