ASCO 2018: PECULIAR: An Open Label, Multicenter, Single-arm, Phase 2 Study of Neoadjuvant Pembrolizumab and Epacadostat, Preceding Radical Cystectomy, for Patients with Muscle-invasive Urothelial Bladder Cancer
In this study, the authors assess pembrolizumab (PEM), which is an EMA and FDA-approved therapy for metastatic UC after platinum failure or for cisplatin-ineligible pts, and epacadostat (EPA), an anti-IDO1 agent, which when combined with PEM, safely improved the response-rate in UC in a phase 1 trial.
As neoadjuvant chemotherapy (cisplatin based chemotherapy) is so underutilized despite Level 1 evidence suggesting a 5-7% survival benefit, they are examining the efficacy of this combination in the neoadjuvant setting – in the hopes that a safe, effective alternative may increase utilization.
Study Design: Open-label, Single-arm, Phase II study
Eligibility:
Patients with cT2-T3b N0 M0 urothelial carcinoma – cisplatin eligible patients included
Treatment:
3 cycles of PEM 200mg intravenously, q3 weekly
EPA will be orally taken at the dose of 100 mg BID, from d1 until 10 days before cystectomy.
Cystectomy should be performed within 3 weeks of the last PEM dose
Patients will be followed with computed tomography (CT) scan, 18FDG-PET/CT scan, and multiparametric bladder MRI (mpMRI), which will be done during screening and before cystectomy to stage and evaluate response.
After cystectomy, pts will be managed according to EAU guidelines.
Adjuvant anti PD-1 therapy is not allowed.
Outcomes:
PD-L1 status will be assessed using Dako anti-PD-L1 antibody (clone 22C3), relying on the combined positivity score (CPS).
Pathologic complete response (pT0) is the primary endpoint.
All pts enrolled who receive at least 1 cycle of study drug will be included in the intent-to-treat (ITT) analysis.
A MinMax 2-stage design will be used to estimate the number of patients required. The total number of patients expected is 71. In the first stage of 43 patients, ≥6 pT0 will be required in the first stage, and ≥14 pT0 in the whole study population.
They are also collecting tissue and blood samples to complete correlative research on immune-cell profiling and cytokine assessment. In tumor samples, genomic analyses will be done with FoundationONE test (Foundation Medicine Inc.). Tumor mutational burden (TMB) will be determined on 1.1 Mbp of sequenced DNA and reported as mutations (mut) per megabase (Mb) and microsatellite instability (MSI) will determined on 114 loci (EudraCT number).
No poster was submitted by the authors, so the above is based on the submitted abstract alone.
Presented by: Andrea Necchi, MD
Written by: Thenappan Chandrasekar, MD, Clinical Fellow, University of Toronto, Twitter: @tchandra_uromd at the 2018 ASCO Annual Meeting - June 1-5, 2018 – Chicago, IL USA