Exploring C-reactive protein (CRP) dynamics and resistance to immunotherapy in bladder cancer

Lead Investigator: Matthew Galsky, Icahn School of Medicine at Mount Sinai
Title of Proposal Research: Exploring C-reactive protein (CRP) dynamics and resistance to immunotherapy in bladder cancer
Vivli Data Request: 10046
Funding Source: None
Potential Conflicts of Interest: None

Summary of the Proposed Research:

Urothelial cancer is a type of cancer that occurs in the urothelial cells, which line the inside of the bladder, ureters, urethra, and part of the kidneys. Each year about 600,000 new cases of bladder cancer are diagnosed worldwide. New treatments like immunotherapy, medical treatments that use your body’s own immune system to fight diseases, have made a significant difference in treating metastatic urothelial cancer (cancer that has spread from its original location). However, not everyone responds well to these treatments. We need to better understand better why some patients do not respond to treatment. Inflammation is a common feature of cancer. Our research found that certain aspects of the tumor’s environment, related to inflammation, are linked to immunotherapy resistance, which is when cancer does not respond to treatment that aims to use the body’s immune system to fight it.

Previous studies showed that high levels of a protein in the blood called C-Reactive Protein (CRP), which indicates inflammation, is linked to resistance to immunotherapy treatment. We will explore the association between tumor inflammation and immunotherapy outcomes in patients with bladder cancer, we will analyze data from three clinical trials using atezolizumab treatment. Atezolizumab is a medicine used to treat bladder cancer. It works by sticking to a protein called programmed death ligand 1 (PD-L1) on the surface of some cancer cells. We chose to study the data from patients treated with atezolizumab because this medicine is commonly used to treat bladder cancer.

Tumor inflammation will be assessed by evaluating blood C-reactive protein (CRP) levels, a widely recognized biomarker of inflammation. We will examine the data from IMvigor 211, IMvigor 130 and IMvigor 210, and IMvigor 210 cohort 2 clinical trials to determine if varying blood CRP levels correlate with differential treatment outcomes in these patients.

Evaluating CRP levels in the blood of patients enrolled in prior clinical trials will allow us to understand if CRP relates to how well treatment works and whether it can be used to predict patient response to treatment.

Requested Studies:

A Phase II, Multicenter, Single-Arm Study of Atezolizumab in Patients With Locally Advanced or Metastatic Urothelial Bladder Cancer
Data Contributor: Roche
Study ID: NCT02108652
Sponsor ID: GO29293 (Cohort 2)

A Phase III, Open-Label, Multicenter, Randomized Study to Investigate the Efficacy and Safety of Atezolizumab (Anti-PD-L1 Antibody) Compared With Chemotherapy in Patients With Locally Advanced or Metastatic Urothelial Bladder Cancer After Failure With Platinum-Containing Chemotherapy
Data Contributor: Roche
Study ID: NCT02302807
Sponsor ID: GO29294

A Phase III, Multicenter, Randomized, Placebo-Controlled Study of Atezolizumab (Anti-PD-L1 Antibody) as Monotherapy and in Combination With Platinum-Based Chemotherapy in Patients With Untreated Locally Advanced or Metastatic Urothelial Carcinoma
Data Contributor: Roche
Study ID: NCT02807636
Sponsor ID: WO30070

A Phase II, Multicenter, Single-Arm Study of Atezolizumab in Patients With Locally Advanced or Metastatic Urothelial Bladder Cancer
Data Contributor: Roche
Study ID: NCT02951767
Sponsor ID: GO29293 (Cohort 1)