Summary: Roche’s VENTANA CLDN18 (43-14A) RxDx Assay, now FDA-approved, identifies CLDN18 protein expression in gastric and gastroesophageal junction cancer patients, to determine eligibility for targeted treatment with VYLOY (zolbetuximab).

Takeaways:

  1. The VENTANA CLDN18 (43-14A) RxDx Assay is the first FDA-approved companion diagnostic for identifying patients with CLDN18.2-positive gastric or GEJ adenocarcinoma, eligible for targeted therapy with VYLOY.
  2. The assay helps guide treatment decisions, particularly for patients with HER2-negative advanced or metastatic gastric/GEJ cancers, offering personalized care options.
  3. Clinical studies showed that patients with CLDN18.2-positive tumors treated with zolbetuximab and chemotherapy experienced up to a 31% reduction in disease progression or death.

Roche announced 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 tumors of patients with gastric or gastroesophageal junction (GEJ) adenocarcinoma. 

These patients now may be eligible for treatment with Astellas’ targeted therapy VYLOYTM (zolbetuximab).

CDx for Gastric or Gastroesophageal Junction Cancer Patients

“Patients who are diagnosed with gastric or gastroesophageal junction cancer are often diagnosed in an advanced stage as early symptoms can be similar across several conditions,” says Jill German, head of Pathology Lab at Roche Diagnostics. “Our companion diagnostic for CLDN18 can help identify patients eligible for targeted treatment and provide them with additional therapeutic options. With the launch of this test, Roche continues to advance personalised healthcare by expanding our innovative companion diagnostic portfolio.”

Current guidelines for gastric/GEJ cancer recommend using biomarkers to guide therapeutic decision making. 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. VYLOY is the first FDA-approved treatment specifically targeting HER2-negative locally advanced unresectable or metastatic gastric or GEJ cancer patients whose tumors are CLDN18.2-positive. 

Gastric cancer is the fifth most common cancer and the fourth leading cause of cancer deaths worldwide.(1) In the U.S., 62% of gastric/GEJ cancer cases are advanced when initially diagnosed, contributing to a five-year overall survival rate of only 6%.(2,3) Although gastric/GEJ cancer is less prevalent in the U.S. than in other parts of the world, it is often diagnosed late as signs and symptoms are common to other conditions.(4)

Further reading: Roche Expands Digital Pathology Platform with AI-Driven Algorithms

VENTANA CLDN18 (43-14A) RxDx Assay

The VENTANA CLDN18 (43-14A) RxDx Assay is a qualitative immunohistochemical assay intended to be used in the assessment of Claudin 18 (CLDN18) protein in gastric adenocarcinoma including gastroesophageal junction (GEJ) adenocarcinoma. 

The OptiView DAB IHC Detection Kit is used for staining on a BenchMark ULTRA instrument. The assay is indicated as an aid in identifying patients with gastric or GEJ adenocarcinoma who may be eligible for treatment with VYLOY (zolbetuximab) in accordance with the approved therapeutic product labelling. The Roche test measures expression of both variants of the CLDN18 protein (18.1 and 18.2 isoforms). CLDN18.2 is the predominant variant expressed in gastric and GEJ cancers.(5,6)

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 tumors were CLDN18.2 positive. CLDN18.2 positivity is defined as ≥ 75% of tumor cells demonstrating moderate to strong membrane CLDN18 staining as measured by the VENTANA CLDN18 (43-14A) RxDx Assay.  In these studies, approximately 38% of gastric/GEJ cancer patients expressed high levels of CLDN18 and were considered CLDN18.2 positive by the VENTANA CLDN18 (43-14A) RxDx Assay. Patients who received a combination of zolbetuximab and chemotherapy experienced a 25-31% reduction in disease progression or death.(7,8) 

References:

  1. Sung H et al. CA Cancer J Clin 2021;71:209-49.
  2. ACS. Cancer Facts & Figures 2022. https://www.cancer.org/content/dam/cancer-org/research/cancer-facts-and-statistics/annual-cancer-facts-and-figures/2022/2022-cancer-facts-and-figures.pdf. Accessed 01-12-2022.
  3. NCI SEER Cancer stat facts: stomach cancer. https://seer.cancer.gov/statfacts/html/stomach.html. Accessed 11-30-2023.
  4. National Cancer Institute. Gastric Cancer Treatment (PDQ)-Patient Version. Accessed at https://www.cancer.gov/types/stomach/patient/stomach-treatment-pdq on March 8, 2023.
  5. Saito, T. Matsuda, D. Moran, P-114 Claudin 18 isoform expression in gastric  adenocarcinoma and pancreatic adenocarcinoma, Annals of Oncology, Volume 32, Supplement 3, 2021, Page S138, ISSN 0923-7534, https://doi.org/10.1016/j.annonc.2021.05.169.
  6. VENTANA CLDN18 (43-14A) RxDx Assay Package Insert, 2023
  7. Astellas press release, Astellas to Present Positive Findings from Phase 3 SPOTLIGHT Trial of Zolbetuximab during 2023 ASCO GI Cancers Symposium. https://www.astellas.com/en/news/26946. Accessed June 12, 2023.
  8. Astellas press release, Astellas Announces Positive Findings from Phase 3 GLOW Trial of Zolbetuximab during March ASCO Plenary Series. https://www.astellas.com/en/news/27481. Accessed June 12, 2023.