TEST:

VENTANA CLDN18 (43-14A) Assay

CLDN18.2 was not significantly associated with PD-L1 or HER2 status regardless of histological subtype (P > 0.05). This study characterized the histological profile of CLDN18.2-positive G/GEJ and broadened our understanding of subgroups likely to benefit from CLDN18.2-targeted therapy.

The significant heterogeneity in poorly cohesive cases and an inverse correlation with signet ring cell content pose diagnostic challenges for pathologists. Moreover, the association between CLDN18.2 positivity and worse progression-free survival in intestinal adenocarcinoma supports a potential role in tumor progression and metastasis, warranting further research.

Patients identified for eligibility using the VENTANA CLDN18 (43-14A) RxDx Assay demonstrated statistically significant improvement in progression-free survival and overall survival with zolbetuximab plus chemotherapy in both phase 3 trials. The VENTANA CLDN18 (43-14A) RxDx Assay demonstrated robust, reproducible analytical performance and clinical utility as a companion diagnostic for first-line zolbetuximab plus chemotherapy in patients with HER2-negative, LA unresectable or mG/GEJ adenocarcinoma whose tumors are CLDN18.2-positive.

Staining quality was the major factor for successful analysis; interpretation errors were not significant. Ongoing quality assurance will enable establishment of appropriate staining protocols and accurate CLDN18.2 interpretation, thereby facilitating individually optimized treatment.

The present study suggests that a subset of patients with CCA exhibited a marked expression of CLDN18.2. These findings underline the need to perform a clinical study evaluating the efficacy of anti-CLDN18.2 therapy in patients suffering from CCA.

Characterizing unresectable, metastatic, or recurrent GC with positive CLDN18.2 expression and evaluating intratumoral heterogeneity and prognostic implications of various therapeutics help advance treatment strategies and develop new therapies for patients with GC.

"Roche...announced today that the VENTANA CLDN18 (43-14A) RxDx Assay is the first U.S. Food and Drug Administration (FDA) approved immunohistochemistry (IHC) companion diagnostic for determining CLDN18 protein expression in tumours of patients with gastric or gastroesophageal junction (GEJ) adenocarcinoma. These patients now may be eligible for treatment with Astellas' targeted therapy VYLOY (zolbetuximab)....VYLOY is the first FDA-approved treatment specifically targeting HER2-negative locally advanced unresectable or metastatic gastric or GEJ cancer patients whose tumours are CLDN18.2-positive."

"Roche...announced today that the VENTANA CLDN18 (43-14A) RxDx Assay is the first immunohistochemistry (IHC) companion diagnostic test to receive CE Mark approval for determining CLDN18 protein expression in tumours of patients with gastric or gastroesophageal junction (GEJ) adenocarcinoma. These patients now may be eligible for treatment with Astellas’ targeted therapy VYLOY (zolbetuximab)...The new VENTANA CLDN18 (43-14A) RxDx Assay can help determine CLDN18.2 status and inform clinicians about the likelihood of patients benefiting from CLDN18.2 targeted therapy...The approval of the VENTANA CLDN18 (43-14A) RxDx Assay is based on the results of the SPOTLIGHT and GLOW clinical studies where it was used as the enrollment assay to identify patients whose tumours were CLDN18.2 positive."

This study provides a comprehensive evaluation of CLDN18.2 status and its correlation with the clinicopathologic characteristics of patients with stages II-IV GC in Korea and with crucial biomarkers. It may be valuable for guiding future drug development, expanding treatment options, and ultimately improving patient outcomes in GC.

CLDN18::ARHGAP fusions characterize GECs with distinct clinical and biologic features. Future studies will determine if these cancers can expand the pool of patients considered for CLDN18-targeted therapy.

We demonstrated a concordant analytical performance between the tested CLDN18/CLDN18.2 IHC assays in GC. Their implementation in the clinical setting might help identify patient candidates that could benefit from treatment with CLDN18.2 targeted therapies. Additional research is needed to confirm similar analytical performance between the three IHC assays in other indications.

CLDN18.2-targeted treatment with zolbetuximab in combination with chemotherapy has recently been assessed in two phase III studies of patients with HER2-negative, locally advanced, unresectable or metastatic gastric or gastroesophageal junction adenocarcinoma...It also failed to meet the threshold for accuracy and sensitivity when used on either the Dako or the Leica platforms. These results demonstrate the reliability of IHC testing for CLDN18 expression in gastric tumor samples, when using commercially available platforms with an appropriate methodology and primary antibody selection.