NCT03263039

Biomarkers in Urothelial Cancer Patients Treated With Pembrolizumab

Biomarker Discovery Study to Identify Patients With Advanced Urothelial Cancer Benefitting From Pembrolizumab Treatment

• Status: Unknown
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 80 (estimated)
• Sponsor: Erasmus Medical Center · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

In the RESPONDER study, the role of the immune evasive mechanisms combined with genomic characterization will be explored in urothelial cancer patients treated with second-line treatment with pembrolizumab. Combined profiling of immune and molecular status is novel and may contribute to improved patient stratification and provide rationale for future treatment strategies containing pembrolizumab.

Detailed description

Antibodies that target the crosstalk between immune and cancer cells by inhibiting programmed death 1 (PD-1, Pembrolizumab and Durvalumab) or programmed death-ligand 1 (PD-L1, Atezolizumab) have shown promising results as second-line treatments in phase II studies with response rates of about 30%. Although urothelial cancer is prone to immune checkpoint blockade, better understanding of the underlying mechanisms is necessary to improve patient selection. The efficacy of immune checkpoint inhibitors in urothelial cancer may be affected by both tumor specific and environmental factors. In order to improve the efficacy of immunotherapy in urothelial cancer, drivers of local immune suppression need to be identified. In this prospective translational multicenter study, clinical data, peripheral blood and sequential tumor biopsies are collected from urothelial cancer patients treated with second-line treatment with pembrolizumab to identify the role of immune evasive mechanisms combined with genomic characterization. A pre-treatment tumor biopsy and blood sample will be obtained and subsequently whole genome sequencing and whole genome RNA sequencing is performed. Both tumor tissue as well as peripheral blood will be investigated for immune and molecular profiling. A biopsy will also be taken after start of treatment (at 6 weeks) and at progression (optional) For future research projects, longitudinal blood samples will be collected for isolation of immune cells, cytokine/chemo-attractants and circulating tumor DNA (ctDNA).

Conditions

• Transitional Cell Carcinoma of the Bladder
• Biomarkers

Interventions

Type	Name	Description
DRUG	Pembrolizumab	Pembrolizumab 200 mg Q3W

Timeline

• Start date: 2017-08-21
• Primary completion: 2022-08-19
• Completion: 2023-08-19
• First posted: 2017-08-28
• Last updated: 2021-08-20

Locations

1 site across 1 country: Netherlands