An Epidemiologic Study on PD-L1 Expression Combined With Clinical Observation in the Chinese MIUBC Patients. (POLARIS)

An Epidemiologic Study on PD-L1 Expression Combined With Clinical Observation of Initial Treatment Pattern and Overall Survival in the Chinese Muscle Invasive Urothelial Bladder Carcinoma Patients.

The Primary Objective of this observational study is to investigate the prevalence of high PD-L1 expression in Chinese MIUBC patients.

Study Overview

• Status: Completed
• Conditions: Urinary Bladder Cancer

Detailed Description

The primary objective of this observational study is:

•To investigate the prevalence of high PD-L1 expression in Chinese MIUBC patients. High PD-L1 expression is defined as ≥25% tumor cell membrane positivity for PD-L1 at any intensity above background staining as noted on the corresponding negative control OR ≥25% tumor associated immune cell positivity for PD-L1 at any intensity above background staining as noted on the corresponding negative control.

Note: PD-L1 High (>=25% tumor cell membrane positivity for PD-L1 or 1) IF IC area >1%: >=25% tumor associated immune cell positivity for PD-L1; 2) If IC area=1%: 100% tumor associated immune cell positivity for PD-L1). PD-L1 Low if criteria not met for PD-L1 High.

The second objectives of this observational study are:

• To investigate the PD-L1 expression profile in TC or IC in Chinese MIUBC patients.
• To assess the concordance of PD-L1 testing results generated from the hospital labs with those from the central lab.
• To observe the initial treatment pattern for MIUBC patients in usual clinical practice in China.
• To observe 2-year OS of the Chinese MIUBC patients.

The exploratory objectives of this observational study are:

• To explore the relationship between the demographic characteristics and expression of PD-L1 and other exploratory biomarkers including immune cell (IC) subset CD8+ T cells and tumor mutation burden (TMB).
• To explore the relationship between OS and the demographic characteristics as well as the expression of biomarkers.
• To explore the relationship between PD-L1 and TMB, PD-L1 and CD8 positive T cell respectively.

• Study Type: Observational
• Enrollment (Actual): 248

Contacts and Locations

Study Locations

• China
  • Beijing, China, 100730
    • Research Site
  • Beijing, China, 100034
    • Research Site
  • Changchun, China, 130021
    • Research Site
  • Changsha, China, 410013
    • Research Site
  • Chengdu, China, 610041
    • Research Site
  • Guangzhou, China, 510120
    • Research Site
  • Guangzhou, China, 510060
    • Research Site
  • Hangzhou, China, 310014
    • Research Site
  • Jinan, China, 250012
    • Research Site
  • Meizhou, China
    • Research Site
  • Nanjing, China, 2100008
    • Research Site
  • Shanghai, China, 200032
    • Research Site
  • Shanghai, China, 200072
    • Research Site
  • Shenyang, China, 110001
    • Research Site
  • Wuhan, China, CN-430030
    • Research Site
  • Xiamen, China, 361003
    • Research Site
  • Zhengzhou, China, 450052
    • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Probability Sample

Study Population

Patients with a new diagnosis of MIUBC

Description

Inclusion Criteria:

• Age ≥18 years at the time of screening.
• Be able and willing to sign the informed consent form (ICF).
• Patients with histologically or cytologically documented, muscle invasive urothelial carcinoma (ie, T2 toT4, any N, any M) of bladder (see National Comprehensive Cancer Network [NCCN] Bladder Cancer Guidelines), who had not been previously treated with any systemic chemotherapy, radiotherapy, investigational product, or biologic therapy for cancer treatment.
• For PD-L1 testing by IHC assay, all patients were able to provide a newly acquired tumor sample within 60 days before enrollment by cystectomy, transurethral resection or biopsy. Samples with limited tumor content and fine needle aspirate specimens were not acceptable. Specimens from metastatic bone lesions were typically unacceptable unless there was a significant soft tissue component. The tumor specimen submitted to establish PD-L1 status should be of sufficient quantity to allow for PD-L1 IHC analyses and was preferred in FFPE blocks.

Exclusion Criteria:

• Prior acquiring tumor tissue samples exposure to immune-mediated therapy (including Bacillus Calmette Guerin), including but not limited to, any anti-CTLA-4, anti-PD-1, anti-PD-L1, or anti PD L2 antibodies, therapeutic anticancer vaccines.
• Any concurrent chemotherapy, investigational product, or biologic therapy for cancer treatment. Note: Local treatment of isolated lesions, excluding target lesions, for palliative intent was acceptable (eg, local surgery or radiotherapy).

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
the prevalence of High PD-L1 expression in the MIUBC patients	Tumor tissue will be collected from all eligible patients who sign the ICF. Samples will be tested for PD-L1 expression status.	Tumor tissue samples should be acquired within 60 days before the enrollment and available for testing.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of patients with different PD-L1 expression level	Proportion of patients with different PD-L1 expression level	Tumor tissue samples should be acquired within 60 days before the enrollment and available for testing.
PD-L1 testing concordance between central lab and hospital labs	PD-L1 testing concordance between central lab and hospital labs	Tumor tissue samples should be acquired within 60 days before the enrollment and available for testing.
Distribution percent of different treatment approaches	Distribution percent of different treatment approaches	enrollment visit
2-year OS	follow up for OS up to 2 years from the baseline	From enrollment to OS, up to 2 years

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
The prevalence of PD-L1 expression by subgroups	The prevalence of PD-L1 expression by subgroups according to age, gender, primary tumor site, metastatic disease, at baseline, and prior tobacco use, etc	enrollment visit
OS by subgroups	OS by subgroups according to age, gender, primary tumor site, metastatic disease at baseline and the PD-L1 expression of high and low/negative as well as other biomarkers, etc. Simple correlation coefficients among biomarkers including PD-L1 with TMB, PD-L1 with CD8+ T cell, PD-L1+ IC with CD8+ T cell.	from enrollment to OS, up to 2 years
Simple correlation coefficients among biomarkers	Simple correlation coefficients among biomarkers including PD-L1 with TMB, PD-L1 with CD8+ T cell, PD-L1 positive IC with CD8+ T cell.	enrollment visit

Collaborators and Investigators

• Sponsor: AstraZeneca
• Investigators: Principal Investigator: Liqun ZHOU, doctor, Peking University First Hospital

Publications and helpful links

Helpful Links

• CSR synopsis_redacted and confirmd by GSD

Study record dates

Study Major Dates

• Study Start (Actual): May 18, 2020
• Primary Completion (Actual): March 27, 2023
• Study Completion (Actual): March 27, 2023

Study Registration Dates

• First Submitted: February 9, 2018
• First Submitted That Met QC Criteria: February 9, 2018
• First Posted (Actual): February 15, 2018

Study Record Updates

• Last Update Posted (Actual): March 27, 2024
• Last Update Submitted That Met QC Criteria: March 26, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Urologic Diseases; Urinary Bladder Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Urinary Bladder Neoplasms
• Other Study ID Numbers: D9012R00001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Chinese Laws and Regulations don't allow

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No