Presentation Authors: Shaheen Alanee*, Detroit, MI, Ahmed El-Zawahry, Springfield, IL, kevin McVary, Maywood, IL, Mustafa Deebajah, Detroit, MI, Sherjeel Sana, Kathy Robinson, Krishna Rao, Springfield, IL
Introduction: A phase I trial of intravesical bacillus Calmette-Guerin (BCG) in combination with systemic pembrolizumab was conducted in patients with high grade non-muscle invasive bladder cancer who had persistent or recurrent disease after failing treatment with at least 2 courses of intravesical therapy (one of which had to contain BCG) or BCG followed by maintenance BCG. The primary objective was to determine the safety of this combination. Secondary end points included response to treatment at 19 weeks (end of treatment) and 3 months post treatment.
Methods: A total of 12 patients were consented and 10 patients with recurrent/persistent high-grade non-muscle invasive bladder cancer after at least two courses of intravesical therapy or one course of BCG treatment followed by one course of maintenance BCG received treatment. Six doses of pembrolizumab (100 vs 200 mg) were given every 3 weeks over 16 weeks given concurrently with 6 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. Bladder biopsy was performed in patients with suspicious lesions.
Results: 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. All AE were grade 1 or 2. Two patients died during the trial period. One patient died due to progression of upper urinary tract urethelial carcinoma. The second patient died after cystectomy (for progressive disease) from a cardiovascular event. Of the first 9 patients, 7 (78%) had no evidence of disease in the bladder at 19 weeks, end of treatment. The tenth patient is still in treatment.
Conclusions: The combination of BCG and Pembrolizumab was well tolerated. Intravesical BCG and pembrolizumab may have clinical activity in non-muscle invasive bladder cancer recurring after repeated intravesical therapy. A phase III trial will soon open to test the clinical activity of this combination (KEYNOTE-676).
Source of Funding: MERCK & CO