Background
Intravenous immune checkpoint inhibition is an effective anticancer strategy for bacillus Calmette-Guérin (BCG)-unresponsive non-muscle-invasive bladder cancer (NMIBC) but may be associated with greater systemic toxicity compared with localized therapies.
Conclusions
We demonstrate that intravesical pembrolizumab is safe, feasible, and capable of eliciting strong immune responses in a clinical setting and should be investigated further. Patient summary: Direct application of pembrolizumab to the bladder is a promising alternative for non-muscle-invasive bladder cancer unresponsive to Bacillus Calmette-Guérin and should be investigated further.
Objective
We assessed the safety and antitumor activity of intravesical pembrolizumab combined with BCG. Design, setting, and participants: A 3 + 3 phase 1 trial of pembrolizumab + BCG was conducted in patients with BCG-unresponsive NMIBC (NCT02808143). Intervention: Pembrolizumab was given intravesically (1-5 mg/kg for 2 h) beginning 2 weeks prior to BCG induction until recurrence. Urine profiling during treatment and spatial transcriptomic profiling of pre- and post-treatment tumors were conducted to identify biomarkers that correlated with response. Outcome measurements and statistical analysis: Safety and tolerability of immune checkpoint inhibition were assessed, and Kaplan-Meier survival analysis was performed.