SUO 2019: Phase I Trial of Intravesical Bacillus Calmette-Guérin Combined with Intravenous Pembrolizumab in High Grade Nonmuscle Invasive Bladder Cancer

Washington, DC ( There is a need for a new line of treatment for BCG unresponsive superficial high-grade non-muscle invasive bladder cancer (NMIBC). Both BCG and anti-PD1 agents have proven activity in urothelial cancer, and upcoming trials are looking at monotherapy or combination therapy with these agents to provide an alternative to radical cystectomy. At the 20th Annual Meeting of the Society of Urologic Oncology, during the Young Urologic Oncologists Podium Session, Dr. Shahee Alanee, presented the results of Phase I Trial of Intravesical BCG Combined with Intravenous Pembrolizumab in High-Grade NMIBC. Patients who had persistent or recurrent disease after failing treatment with at least two courses of intravesical therapy (one of which had to contain BCG) or BCG followed by maintenance BCG, were included in the study. The primary objective was to determine the safety of this combination, and the secondary endpoints were the response to treatment at 19 weeks (end of treatment).

Dr. Alanee then described the inclusion and exclusion criteria; good performance status was essential. A total of 18 patients were enrolled, and ten patients with recurrent/persistent high-grade NMIBC after at least two courses of intravesical therapy or one course of BCG treatment followed by one course of maintenance BCG finished treatment. Six doses of pembrolizumab (100 vs. 200 mg) were given every three weeks over 16 weeks, given concurrently with six weekly doses of BCG beginning at week 7. Patient safety was evaluated during and for 30 days following pembrolizumab treatment. Preliminary combination efficacy was determined at 19 weeks using cystoscopy, and a bladder biopsy was performed in patients with suspicious lesions.

Dr. Alanee then highlighted the results of this phase I trial. All patients with CIS responded to therapy, and the overall response rate was 67%. The combination of BCG and pembrolizumab was well tolerated at both 100mg and 200mg fixed doses. Fatigue and dysuria, spasm, urgency, sensitivity, and frequency were the most common adverse events reported, with 5 grade III and 2 grade IV adverse events. Two deaths were reported during the trial period; one patient died due to the progression of upper urinary tract urothelial carcinoma, and the second patient died after cystectomy (for progressive disease) from a cardiovascular event.

Dr. Alanee concluded that the combination of BCG and Pembrolizumab was well tolerated and showed acceptable safety. A phase III trial is now open to test the clinical activity of this combination. Dr. Alanee also alluded to the future directions of this study, which includes gene expression and analysis of baseline immune profile. Results of the immune profiling of serial urine and blood samples will be submitted to future meetings.

Presented by: Shaheen Alanee, MD, MPH, MBA, Urologist, Detroit, Michigan, USA.

Written by: Abhishek Srivastava, MD, Society of Urologic Oncology Fellow, Fox Chase Cancer Center, Fox Chase Cancer Center, Philadelphia, PA Twitter: @shekabhishek at the 20th Annual Meeting of the Society of Urologic Oncology (SUO), December 4 - 6, 2019, Washington, DC