Overview on Keynote 57: "Phase II trial of Pembrolizumab (pembro) for patients (pts) with high-risk (HR) nonmuscle invasive bladder cancer (NMIBC) unresponsive to bacillus calmette-guérin (BCG)"

Watch the video interview with Dr. Balar on Keynote 57.

Aim of the study

To evaluate the efficacy of Pembrolizumab in patients with non-muscle invasive bladder cancer (NMIBC) unresponsive to Bacillus Calmette-Guerin (BCG) therapy. The primary study hypothesis is that treatment with pembrolizumab will result in a clinically meaningful response.

Primary end-points are:

• Complete response rate (defined as the absence of high-risk NMIBC), in cohort A
• Disease-free survival rate, in cohort B

Secondary end-point:

• Complete response rate (defined as the absence of any disease), in cohort A
• Duration of response, in cohort A
• Safety/tolerability

Design of the study
Single-arm phase 2 study for patients with BCG-unresponsive NMIBC who were unwilling or unfit to undergo radical cystectomy.

Patients are divided into two cohorts:

• Cohort A (n=130): patients with carcinoma in situ (CIS) with or without papillary disease (high-grade Ta or T1)
• Cohort B (n=130): papillary disease (high-grade Ta or T1) without CIS

Included patients receive pembrolizumab 200mg, intravenously, every 3 weeks until one of the following events:

• Recurrence of high-risk NMIBC
• Progression of disease
• 24 months

The efficacy of pembrolizumab is evaluated with cystoscopy and cytology ± biopsy every 3 months for the first two years, then every 6 months for other two years, then once yearly

Inclusion criteria
Patients with histologically confirmed high-risk, BCG-unresponsive NMIBC, who already received adequate BCG therapy and who refused radical cystectomy are considered eligible for this study.

BCG-unresponsive disease is defined as follows:

• BCG refractory
  • Stage progression at 3 months after adequate BCG induction (high-grade T1 at 3 months after initial CIS or high-grade Ta)
  • Persistent high-risk NMIBC at 6 months despite adequate BCG
• BCG relapsing – recurrence of high-risk NMIBC after the patient achieves a disease-free state within 12 months after adequate BCG therapy

Main findings
The interim results for the cohort A were presented during the Challenges and Advances in Perioperative and Local Therapy for Urothelial Carcinoma session at GU ASCO 2019.

• 102 patients met the inclusion criteria (63.7% of these had CIS alone).
• The 3-months complete response rate was 40.2%.
• Among the 41 patients who achieved a complete response at 3 months, 58.5% maintained a complete response at last follow up (median 16.7 months).
• Among the 41 patients who achieved a complete response at 3 months, 36.6% experienced recurrent NMIBC after initial response.
• No progression to muscle-invasive disease was recorded.