Login to Access Video or Poster Abstract: MP15-12
Sources of Funding: Supported in part through NIH/NCI SBIR Phase I & II grants (CA156740: Wong)

Introduction

The current standard of care (SOC) treatment for patients with high risk NMIBC is a transurethral resection of the bladder tumor or biopsy followed by a 6-week induction course of intravesical BCG treatment and supplementary maintenance instillations approximately every 3 months thereafter (Lamm DL et al, 2000). While clinical response is significantly improved with BCG treatment, 50% of patients are still expected to suffer recurrent disease within the first 12 months (Sfakianos JP, et al 2014). Thus, 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-naive NMIBC patients.

Methods

A dose escalation 3+3 design was employed to evaluate intravesical ALT-803 plus 50 mg BCG in BCG-naive patients with Ta, T1 or Tis stage NMIBC. Patients received intravesical ALT-803 in conjunction with BCG weekly for 6 consecutive weeks (induction phase) and then encouraged (but not required) to receive maintenance BCG alone as per standard practices. Patients then had a routine cystoscopy and voided urinary cytology every 3 months for 2 years to determine confirmatory response assessment. Negative cystoscopy, VUC and/or biopsy yielded a complete response (CR). No cohort (100, 200 or 400 ?g/instillation ALT-803) experienced any dose limiting toxicities.

Results

To date, 100% patients (9/9) are disease-free (CR) at 12 months and continue to be followed for recurrence for up to 2 years. Adverse events (AEs) consistent with SOC BCG treatment such as hematuria and urinary tract pain were reported in all cohorts. One patient in 400 ?g ALT-803 instillation cohort developed a urinary tract infection requiring delay of intravesical treatment by 1 week. No grade 3/4 toxicities were noted and no DLTs were observed in any patients._x000D_ _x000D_

Conclusions

Intravesical ALT-803 plus BCG treatment is safe and well tolerated in BCG-naive patients with NMIBC. All patients are disease-free, 12 months after treatment with BCG and ALT-803. Corollary immune studies are pending and further evaluation in expansion cohorts of a randomized phase II trial is currently underway. Clinical trial information: NCT02138734

Funding

Supported in part through NIH/NCI SBIR Phase I & II grants (CA156740: Wong)