EU Green Lights CLDN18 RxDx Assay As Companion Diagnostic for Zolbetuximab in Gastric Cancer

Matt Sause, CEO of Roche Diagnostics

CE certification was granted to the VENTANA CLDN18 (43-14A) RxDx assay for use as a companion diagnostic to determine Claudin 18 (CLDN18) expression in patients with gastric or gastroesophageal junction (GEJ) adenocarcinoma in the European Union (EU), according to a news release from Roche Diagnostics.¹

The company notes that the assay is the first immunohistochemistry (IHC) test to receive CE marking for this patient population. Accordingly, it can now be used to identify patients with CLDN18.2–positive gastric cancer who may be eligible for treatment with zolbetuximab (Vyloy).

The VENTANA CLDN18 RxDx assay is a qualitative IHC test designed to assess CLDN18 expression in gastric cancer. Staining is performed using the OptiView DAB IHC Detection Kit on a BenchMark ULTRA instrument . The assay detects both 2 protein variants of CLDN18: CLDN18.1 and CLDN18.2. Notably, CLDN18.2 is the primary variant in gastric and GEJ cancers.

Data from the phase 3 SPOTLIGHT (NCT03504397) and GLOW (NCT03653507) trials supported this regulatory decision. In both studies, the VENTANA CLDN18 RxDx test was used to identify patients with CLDN18.2-positive tumors for study enrollment. Approximately 38% of patients with gastric or GEJ cancers met the criteria for CLDN18.2 positivity, defined as 75% or more of tumor cells showing moderate to strong membrane staining.

Findings from SPOTLIGHT showed that zolbetuximab plus mFOLFOX6 produced a median PFS of 10.61 months (95% CI, 8.90-12.48) vs 8.67 months (95% CI, 8.21-10.28) with placebo plus mFOLFOX6 (HR, 0.75; 95% CI, 0.60-0.94; P = .0066).² Similarly, patients treated with zolbetuximab plus CAPOX (n = 254) in the GLOW study experienced a 31.3% reduction in the risk of progression or death compared with placebo plus CAPOX (HR, 0.687; 95% CI, 0.544-0.866; P = .0007).³

"Gastric cancer remains a significant global health challenge. In Europe, only three percent of patients with metastatic disease live beyond five years,” Matt Sause, chief executive officer of Roche Diagnostics, stated in the news release.¹ "Our new companion diagnostic is a significant step forward for patients. By identifying those who may benefit from a targeted treatment, this new test can expand treatment possibilities, and aid clinicians to potentially improve outcomes.”

Gastric cancer is frequently diagnosed at a late stage due to symptoms that overlap with other conditions, leading to an overall survival rate of 25% among patients in the EU. Through the detection of CLDN18.2, an emerging biomarker in this disease space, the Ventana CLDN18 RxDx assay could help predict of the likelihood of a patient responding to treatment with targeted therapy.

In September of 2024, the European Commission approved treatment with zolbetuximab plus fluoropyrimidine- and platinum-containing chemotherapy for the same patient population.⁴ This marked zolbetuximab as the first approved therapy in the EU that targets CLDN18.2 in patients with advanced gastric cancer.

Additionally, the FDA accepted the resubmission of a biologics license application (BLA) seeking the approval of zolbetuximab for the first-line treatment of adult patients with locally advanced unresectable or metastatic, CLDN18.2–positive, HER2-negative gastric or GEJ adenocarcinoma in May 2024. The BLA has a future target action date under the Prescription Drug User Fee Act of November 9, 2024. The resubmission came following a complete response letter issued by the FDA in January 2024 due to third-party manufacturing deficiencies.

Results from the SPOTLIGHT and GLOW trials supported both regulatory decisions.^1-3

References

1. Roche obtains CE certification for the first companion diagnostic to identify patients with gastric and gastroesophageal junction cancer eligible for targeted treatment with VYLOY. News release. Roche Diagnostics. October 11, 2024. Accessed October 11, 2024. https://www.biospace.com/press-releases/roche-obtains-ce-certification-for-the-first-companion-diagnostic-to-identify-patients-with-gastric-and-gastroesophageal-junction-cancer-eligible-for-targeted-treatment-with-vyloy
2. Shitara K, Lordick F, Bang YJ, et al. Zolbetuximab plus mFOLFOX6 in patients with CLDN18.2-positive, HER2-negative, untreated, locally advanced unresectable or metastatic gastric or gastro-oesophageal junction adenocarcinoma (SPOTLIGHT): a multicentre, randomised, double-blind, phase 3 trial [published correction appears in Lancet. 2023;402(10398):290. doi:10.1016/S0140-6736(23)00620-7
4. Shah MA, Shitara K, Ajani JA, et al. Zolbetuximab plus CAPOX in CLDN18.2-positive gastric or gastroesophageal junction adenocarcinoma: the randomized, phase 3 GLOW trial. Nat Med. 2023;29(8):2133-2141. doi:10.1038/s41591-023-02465-7
5. Astellas receives approval from the European Commission for VYLOY (zolbetuximab) in combination with chemotherapy for advanced gastric and gastroesophageal junction cancer. News release. Astellas Pharma. September 20, 2024. Accessed October 11, 2024. https://newsroom.astellas.us/2024-09-20-Astellas-Receives-Approval-from-the-European-Commission-for-VYLOY-TM-zolbetuximab-in-Combination-with-Chemotherapy-for-Advanced-Gastric-and-Gastroesophageal-Junction-Cancer
6. U.S. FDA acknowledges Astellas’ resubmission of biologics license application for zolbetuximab and sets new action date. News release. Astellas Pharma. May 31, 2024. Accessed October 11, 2024. https://www.astellas.com/en/news/29186