183P - Development of a cadherin-17 (CDH17) immunohistochemistry assay for use as a companion diagnostic for cabotamig in gastrointestinal cancers

Background

CDH17 is a highly specific therapeutic target for gastrointestinal (GI) adenocarcinoma. Cabotamig, a bispecific T-cell engager antibody directed against CDH17/CD3, is undergoing phase 1 clinical trial in Hong Kong and Australia for the treatment of advanced GI cancers (NCT05411133). We developed an automated CDH17 immunohistochemistry (IHC) assay as a potential companion diagnostic test (TibDx1).

Methods

The TibDx1 assay was developed and optimized using GeneTech’s NMPA-approved autostainer GS2000 to detect CDH17 expression in FFPE GI cancers tissue. Assay optimization was carried out using several clones of CDH17 antibodies. Assay precision studies including intraday and interday repeatability and antibody lot to lot variation were performed. A digital scoring system which quantified CDH17 expression as M Score was used to determine the positive rate of CDH17 across different GI neoplastic tissues (n=215) in tissue microarray (TMA) slides. A clinical cutoff of ≥10% CDH17 expression in tumor tissue confirmed by a pathologist was established and applied in the phase 1 clinical trial.

Results

The TibDx1 assay demonstrated optimal staining intensity with low background using the TIB-A01 clone antibody. Interlot study showed a 1.86% relative standard deviation (RSD) for M score generation across TIB-A01 antibody batches. Intraday and interday evaluation yielded 5.59% and 7.59% RSD, respectively. TMA M Score data exhibited concordance with published literature, with the highest CDH17 positivity rate for CRC, followed by gastric, esophageal, pancreatic adenocarcinoma, and cholangiocarcinoma. In the clinical trial, 38 patients were screened and 33 were enrolled, with enrolment rates of 100% for CRC and gastric adenocarcinoma, 57% for pancreatic adenocarcinoma, and 67% for liver cancers. Table: 183P

CDH17 positivity of different types of GI cancers and clinical study enrollment rate

¹Altree-Tacha et al 2017, ²Panarelli et al 2012, ³Chen et al 2015, ⁴Lin et al 2014, ⁵Su et al 2008, ⁶Qiu et al 2013, ⁷Park et al 2007, ⁸Ito et al 2005, ⁹Zheng et al 2021, ¹⁰Jacobsen et al 2024

Conclusions

TibDx1 CDH17 IHC assay is a validated and reliable companion diagnostic tool, which facilitates patient selection for the effective use of Cabotamig in GI cancers.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

Arbele Limited.

Funding

Arbele Pty Ltd, Sydney, NSW, Australia; Asian Fund for Cancer Research; Innovation & Technology Fund of HKSAR; HK Science Park & Technology.

Disclosure

All authors have declared no conflicts of interest.