Introduction and objective
We conducted the first phase I dose-escalation trial (NCT02324582) of intravesical Bacillus Calmette-Guérin (BCG) in combination with systemic pembrolizumab in patients with high-grade non-muscle-invasive bladder cancer (HGNMIBC) who had persistent or recurrent disease after prior intravesical therapy with BCG. To assess disease-free survival (DFS) and overall survival (OS), patients from this phase I trial NCT02324582 were followed for approximately 2 years.
Methods
Eighteen patients were consented for the study, five of whom were screen failures. Six doses of pembrolizumab were administered every 3 weeks over 16 weeks concurrently with six weekly doses of BCG beginning at week 7. Patient safety was evaluated from the time of consent through 30 days following pembrolizumab treatment and was reported previously. Clinical activity was determined using cystoscopy and cytology with biopsy of suspicious lesions.
Results
At the updated data cutoff (10/10/2021), the median age of the 13 patients treated was 73 years, 11 were males. Most patients were Caucasians (92.3%). Initial bladder cancer pathology was pT1 in 9 (69.2%), pTa in 3 (23.1%), and carcinoma in situ (CIS) in 1 (7.7%). The pathologic disease stage immediately prior to enrollment (after restaging transurethral resection) was pTa in 6 (46.2%), CIS in 6 (46.2%), and pT1 in 1 (7.7%). At 12 months, the DFS and OS were 69.23%, and 92.31% respectively. At 24 months, the DFS and OS were 38.46% and 92.31% respectively. The attached graph depicts disease free survival rate in our patient population.
Conclusions
We have now established safety and present 2 year response data on our group of subjects treated with BCG combined with intravenous pembrolizumab in patients with recurrent or persistent HGNMIBC. A phase III trial is currently recruiting subjects to test the efficacy of this combination in HGNMIBC (KEYNOTE-676).
Source of funding
Merck