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

Abstract

510 Background: The current standard of care for patients with high risk NMIBC is a TURBT or biopsy followed by a 6-week induction course of intravesical BCG and supplementary maintenance therapies every 3 months thereafter (Lamm 2000). While clinical response is significantly improved with BCG, 50% of patients are still expected to recur within 12 months ( Sfakianos 2014). The pursuit of novel agents to prevent progression and recurrence of NMIBC remains critical. This phase Ib clinical trial evaluates the safety and tolerability of ALT-803, an IL-15 superagonist, plus BCG in BCG-naïve NMIBC patients. Methods: A dose escalation 3+3 design was employed to evaluate intravesical ALT-803 plus 50 mg BCG in BCG-naïve patients with intermediate or high-risk Ta, T1 or Tis stage NMIBC. Patients received intravesical ALT-803 in conjunction with BCG weekly for 6 consecutive weeks (induction) and then encouraged (but not required) to receive maintenance BCG alone as per standard practices. Patients had a routine cystoscopy and voided urinary cytology (VUC) every 3 months for 2 years to determine response. Negative cystoscopy, VUC and/or biopsy yielded a complete response (CR). No cohort (100, 200 or 400 μg/instillation ALT-803) experienced any dose limiting toxicities. Results: All patients are disease-free (CR) at 24 months; no patients experienced disease recurrence or progression. Adverse events consistent with SoC BCG treatment (hematuria and urinary tract pain) were reported in all cohorts. One patient experienced a grade 3 adverse event of hypertension that resolved the same day. No grade 4 toxicities or DLTs were observed. Clinical trial information: NCT02138734. Conclusions: Intravesical ALT-803 plus BCG treatment is well tolerated in BCG-naïve patients with NMIBC. All patients are disease-free 24 months after treatment with BCG and ALT-803. A randomized phase II trial is currently underway.[Table: see text]