A drug called Vyloy (zolbetuximab-clzb) has been approved for use with chemotherapy for the first-line treatment of adults with locally advanced unresectable or metastatic gastric or gastroesophageal junction (GEJ) adenocarcinoma. This treatment combination is for adults whose gastric or GEJ adenocarincoma:
- Is locally advanced and can’t be surgically removed, or has spread to other parts of the body
- Is HER2-negative
- Tests positive for a protein called Claudin 18.2 (CLDN18.2)
FDA also approved the VENTANA CLDN18 (43-14A) RxDx Assay as a companion diagnostic device to identify patients with gastric or GEJ adenocarcinoma who may be eligible for treatment with zolbetuximab.
How It Works
The CLDN18.2 protein is expressed by several types of cancer cells, while not expressed by healthy cells. Zolbetuximab is a chimeric IgG1 monoclonal antibody that binds to CLDN18.2 and mediates cell death through antibody-dependent cellular cytotoxicity and complement-dependent cytotoxicity.
Two Important Studies: SPOTLIGHT and GLOW
These phase 3 trials tested Vyloy combined with different chemotherapy regimens against chemotherapy alone. Both studies met their primary endpoint of progression-free survival and the secondary endpoint of improvement in overall survival. This means patients who received VYLOY lived longer without their cancer getting worse and had better overall survival rates compared to those who only received chemotherapy.
The most common side effects reported in patients taking Vyloy in combination with mFOLFOX6 or CAPOX were nausea, vomiting, fatigue, decreased appetite, diarrhea, peripheral sensory neuropathy, abdominal pain, constipation, decreased wight, hypersensitivity reactions, and pyrexia.
What This Means for Patients
If you have advanced stomach or GEJ cancer, your doctor may test your tumor for the CLDN18.2 protein. Talk to your oncologist about whether this treatment might be right for you. They can explain the potential benefits and side effects, and help you make an informed decision about your care.
More Reading
Zolbetuximab (IMAB362) in Advanced Stomach Cancer
Diagnosed with Gastric Cancer: 10 Tips on How to Get The Most From Your Doctor
Connect With Others for Support and Information
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References
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. Lancet 2023;401(10389):1655-1668. Errata in: Lancet 2023;402(10398):290; Lancet 2024;403(10421):30.
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.
