EAU 2017: PURE01: An open label, single-arm, phase 2 study of the anti-programmed death (PD)-1 monoclonal antibody (moAb) pembrolizumab for neoadjuvant therapy of muscle-invasive urothelial bladder carcinoma (miUBC)

London, England (UroToday.com) After cystectomy, over 40% of patients with muscle invasive urothelial carcinoma (miUBC) will develop a recurrence. Neoadjuvant chemotherapy yields beneficial level 1 evidence, yet it is underutilized worldwide. Pembrolizumab is a humanized IgG4, high-affinity, anti-PD-1 monoclonal antibody that has demonstrated significant activity in metastatic urothelial bladder carcinoma. PDL-1 immunohistochemical (IHC) expression can predict activity of this drug.

Trial investigators hypothesized that neoadjuvant Pembrolizumab, could downstage miUBC and reduce recurrence. Patients with T2-T4a, N0 urothelial bladder carcinoma with residual disease after transurethral resection of the bladder (according to TURB, surgical opinion, cystoscopy or radiological presence) will receive 3 cycles of Pembrolizumab at 200mg every 3 weekly prior to radical cystectomy. Radical cystectomy will be performed within 3 weeks of the last dose (after a total of 9 weeks). CT scan and fluorodeoxyglucose positron emission tomography (FDG-PET)/CT scan will be done during screening and before radical cystectomy.

After radical cystectomy, patients with pT3-4 and/or pN+ disease will be managed according to local guidelines. Further anti PD-1 therapy will not be given post-operatively. PD-L1 status will be assessed on TURB specimen using the anti-PD-L1 Antibody clone 22C3 and a prototype IHC assay and centralized to Qualtek, Goleta, CA. PD-L1 positivity will be defined as any staining in the stroma or in ≥1% of tumor cells.

This trial will use an intention to treat analysis, including all patients who received at least 1 cycle of Pembrolizumab. The primary endpoint is pathologic complete response (pCR). The null hypothesis is that pCR≤10%, while the H1 is pCR> 20%. A 2-stage design will be used to estimate the number of patients required out of the total 90 patients. The first stage will include 49 pts, necessitating ≥6 pCR, and ≥13 pCR in the whole study population (80% power and a 2-sided test of significance at the 10% level).

Additional correlative research on pre- and post-therapy blood samples will be performed and include, multiparametric flow cytometry, Immunohistochemistry, cytokine assessment, and molecular profiling of tumor samples (ClinicalTrials.gov NCT02736266).

Presented by: Necchi A. Mariani L., Anichini A., Giannatempo P., Raggi D. Togliardi E., Calareso G., Nicolai N.6, Crippa F., Biasoni D., Torelli T., Catanzaro M., Stagni S., Piva L., Salvioni R

Written by: Hanan Goldberg, MD, Urologic Oncology Fellow (SUO), University of Toronto
Twitter: @GoldbergHanan

at the #EAU17 -March 24-28, 2017- London, England