A Multicenter, Non-interventional, Descriptive Study to Assess Assay Concordance of HER2 IHC Testing in Chinese Pan-tumor Patients

AstraZeneca2,100 enrolled

Overview

This is a multicenter, non-interventional, descriptive study to retrospectively collect solid tumor samples from focused tumor types (NSCLC, GYN cancers, BTC and UC) and assess both assay concordance and interpretation concordance.

This is a multicenter, non-interventional, descriptive study which included about 2100 patients, a mixture of NSCLC, BTC, GYN cancers and UC, from 12 sites with confirmed diagnosis between 2023 Jan and 2025 Sep. This study includes two phases, which are enrollment phase and assessment phase. In the enrollment phase, all sites will retrospectively collect about 2100 patients (NSCLC \~1,000; BTC \~500; GYN \~450; and UC \~150). Every patient will be tested for HER2 status by 4B5 in local labs. All HER2 results will be reviewed and aligned by a committee of three pathologists using GC algorithms. Based on HER2 results by HercepTest at central lab, patient will be selected for further evaluation in assessment phase. In assessment phase, a total of 320 patients will be included and selected from enrollment phase to meet sample size requirement which is 80 patients with different HER2 expression level (each 20 cases for IHC 0/1+/2+/3+) in NSCLC, BTC, GYN cancers and UC cohorts. In Part I Assay performance evaluation, tissue sample of every patient will be sectioned at least 15 slides and send to central labs for assays evaluation. Interpretation results will be reviewed and aligned by a committee of three pathologists using GC algorithms. Assays and performed platform details are listed below: Roche 4B5 in Ventana platform, MXB\\Zhongshan\\An Biping\\Amoy in Ventana (or Leica) platform (5 assays) v.s. HercepTest in Dako platform. Part II Interpretation concordance evaluation: inter-obsever agreement will be evaluated based on scanned images. Specifically, the first 40 slides (each 10 for 0/1+/2+/3+, each 10 for four disease cohorts) will be selected and digitalized. 36 pathologists, 3 from each site, will be trained for GC interpretation algorithm before joining in the assessment. All slides will be interpreted by all pathologists.

Study Type

OBSERVATIONAL

Enrollment

2,100

Conditions

Pan-tumor(NSCLC, GYN Cancers, BTC and UC)

Eligibility

Sex: ALL

Medical Language ↔ Plain English

Inclusion Criteria: 1. Patients must be at least 18 years of age 2. Male and female patients must have a histological confirmed diagnosis of NSCLC, BTC, GYN cancers, or UC between Jan 01, 2023 and Sep 30, 2025. * For GYN cancers, only cervical cancer, endometrial cancer and ovarian cancer should be included. For each gynecological cancer listed above, at least 5 cases need to be enrolled at each expression level (i.e., IHC 0/1+/2+/3+). 3. Patients must have sufficient archived tumor tissue available, with at least 15 slides suitable for HER2 status determination. Both resection or biopsy samples are acceptable. The age limit of archived tissue blocks is 5 years. Exclusion Criteria: 1. Have a history of other cancers besides NSCLC, BTC, GYN cancers and UC. 2. Specimens of patients that may affect interpretation evaluated by the researcher (e.g., frozen specimens, decalcified specimens, specimens with limited tumor content, etc.)

Locations (11)

Research Site

Beijing, China

RECRUITING

Research Site

Changsha, China

WITHDRAWN

Research Site

Chengdu, China

Outcomes

Primary Outcomes

NPA of HER2 IHC 3+ based on confusion matrix results betwee other assays(Roche 4B5\MXB\Zhongshan\An Biping\Amoy) and HercepTest

To assess the NPA of HER2 IHC 3+ based on confusion matrix results between other assays(Roche 4B5\\MXB\\Zhongshan\\An Biping\\Amoy) and HercepTest

Time frame: From the assessment phase start to the final slides interpreted，up to approximately 6 month

PPA of HER2 IHC 3+ based on confusion matrix results between other assays(Roche 4B5\MXB\Zhongshan\An Biping\Amoy) and HercepTest

To assess the PPA of HER2 IHC 3+ based on confusion matrix results between other assays (Roche 4B5\\MXB\\Zhongshan\\An Biping\\Amoy) and HercepTest

Time frame: From the assessment phase start to the final slides interpreted，up to approximately 6 month

Secondary Outcomes

Inter-observer concordance in binary HER2 negative (IHC 0/1+/2+) and positive status (IHC3+);

To assess the Inter-observer concordance in binary HER2 negative (IHC 0/1+/2+) and positive status (IHC3+);

Time frame: From first slides interpreted to Interpretation concordance evaluation end，up to approximately 6 month

Inter-observer concordance in binary HER2 (IHC 0/1+) v.s. HER2 (IHC 2+/3+);

To assess the Inter-observer concordance in binary HER2 (IHC 0/1+) v.s. HER2 (IHC 2+/3+);

Time frame: From first slides interpreted to Interpretation concordance evaluation end，up to approximately 6 month

Inter-observer concordance in four category HER2 IHC 3+ vs. IHC 2+ vs. IHC 1+ vs. IHC 0

To assess the Inter-observer concordance in four category HER2 IHC 3+ vs. IHC 2+ vs. IHC 1+ vs. IHC 0

Time frame: From first slides interpreted to Interpretation concordance evaluation end，up to approximately 6 month

Central Contacts

AstraZeneca Clinical Study Information Center

CONTACT

1-877-240-9479 information.center@astrazeneca.com

Data from ClinicalTrials.gov

This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.

Research Site

Guangzhou, China

NOT_YET_RECRUITING

Research Site

Haerbin, China

NOT_YET_RECRUITING

Research Site

Jinan, China

NOT_YET_RECRUITING

Research Site

Nantong, China

NOT_YET_RECRUITING

Research Site

Shanghai, China

NOT_YET_RECRUITING

Research Site

Shenyang, China

NOT_YET_RECRUITING

Research Site

Suzhou, China

WITHDRAWN

...and 1 more locations

OPA of HER2 IHC 3+ based on confusion matrix results between other assays and HercepTest

To assess the OPA of HER2 IHC 3+ based on confusion matrix results between other assays and HercepTest

Time frame: From the assessment phase start to the final slides interpreted，up to approximately 6 month

Cohen's kappa of HER2 IHC 3+ based on confusion matrix results between other assays and HercepTest

To assess the Cohen's kappa of HER2 IHC 3+ based on confusion matrix results between other assays and HercepTest

Time frame: From the assessment phase start to the final slides interpreted，up to approximately 6 month

NPA of binary HER2 (IHC 0/1+) v.s. HER2 (IHC 2+/3+), and four category HER2 IHC 3+ vs. IHC 2+ vs. IHC 1+ vs. IHC 0 based on confusion matrix results between other assay and HercepTest, overall and by disease cohort

To assess the NPA of binary HER2 (IHC 0/1+) v.s. HER2 (IHC 2+/3+), and four category HER2 IHC 3+ vs. IHC 2+ vs. IHC 1+ vs. IHC 0 based on confusion matrix results between other assay and HercepTest, overall and by disease cohort

Time frame: From the assessment phase start to the final slides interpreted，up to approximately 6 month

PPA of binary HER2 (IHC 0/1+) v.s. HER2 (IHC 2+/3+), and four category HER2 IHC 3+ vs. IHC 2+ vs. IHC 1+ vs. IHC 0 based on confusion matrix results between other assay and HercepTest, overall and by disease cohort

To assess the PPA of binary HER2 (IHC 0/1+) v.s. HER2 (IHC 2+/3+), and four category HER2 IHC 3+ vs. IHC 2+ vs. IHC 1+ vs. IHC 0 based on confusion matrix results between other assay and HercepTest, overall and by disease cohort

Time frame: From the assessment phase start to the final slides interpreted，up to approximately 6 month

OPA of binary HER2 (IHC 0/1+) v.s. HER2 (IHC 2+/3+), and four category HER2 IHC 3+ vs. IHC 2+ vs. IHC 1+ vs. IHC 0 based on confusion matrix results between other assay and HercepTest, overall and by disease cohort

To assess the OPA of binary HER2 (IHC 0/1+) v.s. HER2 (IHC 2+/3+), and four category HER2 IHC 3+ vs. IHC 2+ vs. IHC 1+ vs. IHC 0 based on confusion matrix results between other assay and HercepTest, overall and by disease cohort

Time frame: From the assessment phase start to the final slides interpreted，up to approximately 6 month

Cohen's kappa of binary HER2 (IHC 0/1+) v.s. HER2 (IHC 2+/3+), and four category HER2 IHC 3+ vs. IHC 2+ vs. IHC 1+ vs. IHC 0 based on confusion matrix results between other assay and HercepTest, overall and by disease cohort

To assess the Cohen's kappa of binary HER2 (IHC 0/1+) v.s. HER2 (IHC 2+/3+), and four category HER2 IHC 3+ vs. IHC 2+ vs. IHC 1+ vs. IHC 0 based on confusion matrix results between other assay and HercepTest, overall and by disease cohort

Time frame: From the assessment phase start to the final slides interpreted，up to approximately 6 month

NPA of HER2 IHC 2+/3+ (IHC 1+ in GYN cancers) based on confusion matrix results between other assay and HercepTest, overall and by disease cohort

To assess the NPA of HER2 IHC 2+/3+ (IHC 1+ in GYN cancers) based on confusion matrix results between other assay and HercepTest, overall and by disease cohort

Time frame: From the assessment phase start to the final slides interpreted，up to approximately 6 month

PPA of HER2 IHC 2+/3+ (IHC 1+ in GYN cancers) based on confusion matrix results between other assay and HercepTest, overall and by disease cohort

To assess the PPA of HER2 IHC 2+/3+ (IHC 1+ in GYN cancers) based on confusion matrix results between other assay and HercepTest, overall and by disease cohort

Time frame: From the assessment phase start to the final slides interpreted，up to approximately 6 month

OPA of HER2 IHC 2+/3+ (IHC 1+ in GYN cancers) based on confusion matrix results between other assay and HercepTest, overall and by disease cohort

To assess the OPA of HER2 IHC 2+/3+ (IHC 1+ in GYN cancers) based on confusion matrix results between other assay and HercepTest, overall and by disease cohort

Time frame: From the assessment phase start to the final slides interpreted，up to approximately 6 month

Cohen's kappa of HER2 IHC 2+/3+ (IHC 1+ in GYN cancers) based on confusion matrix results between other assay and HercepTest, overall and by disease cohort

To assess the Cohen's kappa of HER2 IHC 2+/3+ (IHC 1+ in GYN cancers) based on confusion matrix results between other assay and HercepTest, overall and by disease cohort

Time frame: From the assessment phase start to the final slides interpreted，up to approximately 6 month