Phase I trial of intravesical Bacillus Calmette--Gu'erin combined with intravenous pembrolizumab in recurrent or persistent high-grade non-muscle-invasive bladder cancer after previous Bacillus Calmette--Gu'erin treatment

Article (Faculty180)

cited authors

  • Alanee, Shaheen; Sana, Sherjeel; El-Zawahry, Ahmed; Peabody, James; Pearce, Tiffany; Adams, Nicole; Deebajah, Mustafa; Crabtree, Jane; Delfino, Kristin; McVary, Kevin; others

description

  • <p>Abstract<br>Objectives 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 <br>(HGNMIBC) who had persistent or recurrent disease after prior intravesical therapy with BCG. The primary endpoint was <br>the safety of this combination. The secondary endpoint was clinical activity at three months following BCG treatment.<br>Methods Eighteen patients were consented for the study, five of which were screen failures. Six doses of pembrolizumab <br>were administered every 3 weeks over 16 weeks concurrently with six weekly doses of BCG beginning at week 7. Patient <br>safety was evaluated from the time of consent through 30 days following pembrolizumab treatment. Clinical activity was <br>determined using cystoscopy and biopsy of suspicious lesions.<br>Results Treatment-related adverse events included one grade 4 adverse event (AEs) (adrenal insufficiency). There were <br>nine grade 3 AEs (chest discomfort, pulmonary embolism, arthritis, wrist edema, injection site reaction, bilateral wrist pain, <br>cardiomyopathy, hypokalemia, urinary tract infection). There were 49 grade 1 and 30 grade 2 AEs (88% of AEs). Eleven <br>patients finished the treatment, and two patients died during the study. Of 13 patients treated, nine patients (69%) had no <br>evidence of disease at 3 months following BCG treatment.<br>Conclusions We report for the first time that combining BCG and pembrolizumab in treating HGNMIBC is safe allowing <br>complete treatment of most patients. A phase III trial has opened to test the efficacy of this combination in HGNMIBC</p>

authors

publication date

  • 2021

published in

start page

  • 3807

volume

  • 39