TEST:

VENTANA CLDN18 (43-14A) Assay

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.

The phase 3 SPOTLIGHT (NCT03504397) and GLOW (NCT03653507) studies demonstrated clinically meaningful and statistically significant improvement in progression-free and overall survival with first-line (1L) zolbetuximab (anti-CLDN18.2) + chemotherapy (mFOLFOX6 or CAPOX, respectively) vs placebo + chemotherapy in pts with CLDN18.2+/HER2− disease...Conclusions A high CLDN18.2 prevalence rate (36.4%) was observed in the Asia region which was similar to the global prevalence observed in both the SPOTLIGHT and GLOW phase 3 studies. These data support the relevance of CLDN18.2 as a biomarker in Asian pts with LA unresectable or mG/GEJ adenocarcinoma, for whom zolbetuximab + chemotherapy represents a potential 1L therapy.

Conclusion The VENTANA CLDN18 (43-14A) RxDx Assay met all analytical criteria for performance, demonstrating precision scoring of CLDN18 status in G/GEJ adenocarcinomas. The clinically significant improvements in PFS and OS in CLDN18.2-positive patients, identified by the VENTANA CLDN18 (43-14A) RxDx Assay, support the clinical utility of this assay as a companion diagnostic for reliably identifying patients who may benefit from first-line treatment with the CLDN18.2-targeted therapy zolbetuximab in combination with chemotherapy.

Background Zolbetuximab showed efficacy for gastric cancer with Claudin (CLDN)18.2 expression...Conclusions CLDN18.2 expression was observed in 38% of resected gastric cancer samples, which was consistent with previous reports. CLDN18.2 expression was not related to prognosis and specific relationship was not observed in clinical/molecular characteristics of resected gastric cancer.

The SPOTLIGHT (NCT03504397) and GLOW (NCT03653507) phase 3 studies demonstrated clinically meaningful and statistically significant improvement in PFS and OS with the CLDN18.2-targeted antibody zolbetuximab + chemotherapy (mFOLFOX6 or CAPOX, respectively) vs placebo + chemotherapy as 1L therapy in pts with CLDN18.2+/HER2− disease... Across SPOTLIGHT and GLOW, 3576 pts had valid CLDN18 IHC results; 1399 (39.1%) had CLDN18.2+ tumors. CLDN18.2 prevalence was 43.7% (513/1175) in female pts and 36.9% (886/2401) in male pts. CLDN18.2 prevalence was 44.0% (671/1524) in pts in Europe/Middle East, 37.7% (183/485) in pts in N. America, and 36.5% (479/1314) in pts in Asia Pacific.