Bladder Cancer Program

Division Of Basic Sciences - Nci

Investigators

Linked publications & trials

Abstract

Immunotherapy with immune checkpoint inhibitors, particularly agents targeting the axis of programmed cell death protein 1 and its ligand (PD-1/PD-L1), has improved treatment outcomes in many tumor types. The rationale for assessing immune checkpoint inhibitors in advanced urothelial cancer is supported by a high prevalence of tumor somatic mutations and the presence of PD-L1 expression on tumors and tumor-infiltrating lymphocytes in the tumor microenvironment. Avelumab is a fully human anti-PD-L1 IgG1 antibody that inhibits PD-1/PD-L1 interactions but leaves the PD-1/PD-L2 pathway intact. The first-in-human trial of avelumab was led at the intramural NCI and I led the clinical effort for avelumab in advanced/metastatic urothelial carcinoma which showed clinical benefit, leading to approval by the U.S. Food and Drug Administration (FDA) for this indication. Given the activity of several immune checkpoint inhibitors in this setting, I was eager to test these agents in an earlier disease setting in patients with high-risk muscle-invasive disease. I initiated a phase 3 clinical trial of adjuvant pembrolizumab post-cystectomy in patients with high-risk muscle-invasive urothelial carcinoma of the bladder and upper tract. I am the principal investigator on this Alliance/NCI-sponsored study. The trial is accrued with 702 patients randomized. If positive, would provide a treatment choice for patients with urothelial carcinoma in this setting.