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
- Complete response rate (defined as the absence of any disease), in cohort A
- Duration of response, in cohort A
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
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
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.