Vyloy: Uses, Dosage & Side Effects
A first-in-class monoclonal antibody targeting Claudin 18.2 (CLDN18.2) for the treatment of advanced or metastatic gastric and gastroesophageal junction adenocarcinoma
Vyloy (zolbetuximab) is the first monoclonal antibody to target Claudin 18.2 (CLDN18.2), a tight junction protein expressed on certain gastric and gastroesophageal junction (GEJ) cancer cells. It is approved for adults with locally advanced unresectable or metastatic gastric or GEJ adenocarcinoma whose tumors are CLDN18.2-positive and HER2-negative. Vyloy is administered as an intravenous infusion in combination with fluoropyrimidine and platinum-based chemotherapy. By binding to CLDN18.2, zolbetuximab recruits the immune system to destroy cancer cells through antibody-dependent cellular cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC). Clinical trials (SPOTLIGHT and GLOW) have demonstrated significant improvements in progression-free survival and overall survival with Vyloy-based regimens compared with chemotherapy alone.
Quick Facts: Vyloy
Key Takeaways
- Vyloy (zolbetuximab) is the first approved therapy to target Claudin 18.2 (CLDN18.2), a novel biomarker in gastric and gastroesophageal junction cancer, representing a new class of targeted cancer treatment.
- It is indicated for adults with locally advanced unresectable or metastatic gastric or GEJ adenocarcinoma that is CLDN18.2-positive and HER2-negative, and is always given in combination with fluoropyrimidine and platinum-based chemotherapy.
- Nausea and vomiting are the most common side effects and can be severe; pre-medication with antiemetics before each infusion is essential to help manage these symptoms.
- Patients must undergo biomarker testing to confirm their tumor is CLDN18.2-positive and HER2-negative before starting Vyloy treatment, as the drug only works against cancers expressing this specific protein.
- Clinical trials (SPOTLIGHT and GLOW) demonstrated that adding Vyloy to standard chemotherapy significantly improved both progression-free survival and overall survival compared with chemotherapy alone in eligible patients.
What Is Vyloy and What Is It Used For?
Vyloy contains the active substance zolbetuximab, a chimeric immunoglobulin G1 (IgG1) monoclonal antibody that represents a first-in-class therapeutic approach to gastric cancer treatment. Monoclonal antibodies are laboratory-designed proteins that mimic the immune system’s ability to recognize and attack specific targets. In the case of zolbetuximab, the antibody is engineered to bind with high affinity to Claudin 18.2 (CLDN18.2), a tight junction protein that plays a critical role in cell-to-cell adhesion and is predominantly expressed in normal gastric mucosal cells.
Claudin 18 exists in two isoforms: CLDN18.1, which is primarily found in lung tissue, and CLDN18.2, which is predominantly expressed in differentiated gastric epithelial cells. Under normal physiological conditions, CLDN18.2 is buried within tight junctions between cells and is therefore largely inaccessible to circulating antibodies. However, during malignant transformation in gastric and gastroesophageal junction cancers, the normal tissue architecture is disrupted, exposing CLDN18.2 on the cell surface. Furthermore, many gastric cancers overexpress CLDN18.2, making it an attractive and highly specific therapeutic target. Research indicates that approximately 38% of gastric and GEJ adenocarcinomas are CLDN18.2-positive and HER2-negative, the specific population for which Vyloy is indicated.
When zolbetuximab binds to CLDN18.2 on the surface of tumor cells, it activates two key immune-mediated killing mechanisms. The first is antibody-dependent cellular cytotoxicity (ADCC), in which the antibody recruits natural killer (NK) cells and other immune effector cells to recognize and destroy the cancer cell. The second is complement-dependent cytotoxicity (CDC), in which the antibody activates the complement cascade, a component of the innate immune system, leading to the formation of a membrane attack complex that lyses the tumor cell. Together, these dual mechanisms enable the patient’s own immune system to specifically target and eliminate CLDN18.2-expressing cancer cells.
Vyloy is approved for use in adults with locally advanced unresectable or metastatic gastric or gastroesophageal junction (GEJ) adenocarcinoma. The gastroesophageal junction is the anatomical region where the esophagus (food pipe) meets the stomach. This medication is specifically indicated for patients whose tumors meet two biomarker criteria: they must be positive for CLDN18.2 protein expression and negative for human epidermal growth factor receptor 2 (HER2). The HER2-negative requirement is important because HER2-positive gastric cancers have their own established targeted therapies (such as trastuzumab), and the clinical trials supporting Vyloy’s approval specifically enrolled HER2-negative patients.
Vyloy is always given in combination with other anticancer medicines, specifically fluoropyrimidine-based and/or platinum-based chemotherapy agents. It is not used as a standalone treatment. The approved chemotherapy combinations include mFOLFOX6 (a regimen containing oxaliplatin, leucovorin, and 5-fluorouracil) and CAPOX (capecitabine plus oxaliplatin). The decision on which specific combination to use is made by the treating oncologist based on individual patient factors and clinical guidelines. It is important that patients also read the patient information leaflets for the chemotherapy drugs they are receiving alongside Vyloy.
Before starting Vyloy, your tumor must be tested using a validated immunohistochemistry (IHC) assay to confirm CLDN18.2 positivity and HER2 negativity. This testing is typically performed on a biopsy sample from your tumor. Only patients whose tumors meet both biomarker criteria are eligible for treatment with Vyloy. Your oncologist will arrange this testing as part of the diagnostic workup.
What Should You Know Before Receiving Vyloy?
Contraindications
There is one absolute contraindication for Vyloy. You must not receive this medication if you are allergic (hypersensitive) to zolbetuximab or to any of the other ingredients in the product. The excipients in Vyloy include arginine, phosphoric acid (E 338), sucrose, and polysorbate 80 (E 433). If you have a known allergy to any of these components, inform your doctor before treatment begins.
Warnings and Precautions
Several important warnings and precautions apply to Vyloy treatment. Discuss each of the following with your doctor before and during your course of therapy:
Serious allergic reactions, including anaphylaxis, can occur during or after the infusion of Vyloy. Seek immediate medical attention if you experience hives (itchy, swollen pink or red areas on the skin), persistent cough, breathing difficulties such as wheezing, or throat tightness or voice changes. Your healthcare team will monitor you closely during each infusion and may administer pre-medications to reduce the risk of these reactions.
Severe reactions related to the infusion can occur during or after receiving Vyloy. Symptoms may include nausea, vomiting, abdominal pain, excessive salivation, fever, chest discomfort, chills or rigors, back pain, cough, or hypertension (high blood pressure). If you experience any of these symptoms, tell your doctor or nurse immediately. Your doctor may slow down the infusion rate, temporarily pause the infusion, or discontinue treatment altogether depending on the severity of the reaction.
Nausea and vomiting are very common with Vyloy and can sometimes be severe. Tell your doctor if you are already feeling nauseous before your infusion is scheduled. Your doctor will prescribe antiemetic medications (medicines to prevent nausea and vomiting) before each infusion to help manage these symptoms. If you experience persistent or worsening nausea and vomiting despite pre-medication, contact your healthcare team promptly.
If you experience any of the above symptoms, your doctor may take the following actions depending on the severity:
- Prescribe additional medications to reduce your symptoms or prevent complications
- Reduce the rate at which the infusion is administered
- Temporarily pause or permanently discontinue your Vyloy treatment
Children and Adolescents
There is no relevant use of Vyloy in children and adolescents. Gastric and gastroesophageal junction adenocarcinoma has not been studied in this age group, and the safety and efficacy of zolbetuximab have not been established in patients under 18 years of age.
Pregnancy and Breastfeeding
Vyloy should not be used during pregnancy unless your doctor specifically recommends it after careful consideration of the potential benefits and risks. It is not currently known whether zolbetuximab can harm an unborn baby. If you are pregnant, think you may be pregnant, or are planning to become pregnant, consult your doctor before receiving this medication. Your oncologist will discuss the potential risks and benefits in your individual situation.
Breastfeeding is not recommended during treatment with Vyloy. It is not known whether zolbetuximab or its metabolites pass into human breast milk. Because a risk to the breastfed infant cannot be excluded, you should discuss with your doctor whether to discontinue breastfeeding or to discontinue Vyloy treatment, taking into account the benefit of breastfeeding for your child and the benefit of treatment for you.
Driving and Operating Machinery
Vyloy is not expected to have a significant effect on the ability to drive and use machines. However, if you experience side effects such as nausea, vomiting, fatigue, or dizziness during treatment, exercise caution when driving or operating machinery until these symptoms resolve.
Important Information About Ingredients
Vyloy contains polysorbate 80, which can cause allergic reactions in some individuals. The amount of polysorbate 80 is 1.05 mg per 100 mg dose and 3.15 mg per 300 mg dose. If you have any known allergies to polysorbate or similar substances, inform your doctor before starting treatment.
Vyloy itself does not contain sodium, but a sodium chloride solution (normal saline) is used to dilute the product before infusion. If you have been advised to follow a low-sodium (salt-restricted) diet, discuss this with your doctor or pharmacist.
How Does Vyloy Interact with Other Drugs?
As a monoclonal antibody, zolbetuximab is expected to be eliminated through intracellular catabolism (protein breakdown) rather than by cytochrome P450 (CYP) enzyme metabolism. Therefore, traditional drug-drug interactions mediated by CYP enzymes are unlikely. However, it is important to inform your doctor about all medications you are currently taking, have recently taken, or may plan to take, including prescription drugs, over-the-counter medicines, vitamins, and herbal supplements.
Because Vyloy is always administered in combination with chemotherapy, the potential interactions of the companion chemotherapy agents must also be considered. The fluoropyrimidine and platinum-based drugs used alongside Vyloy have their own interaction profiles, and your oncologist will account for these when planning your treatment regimen.
Known and Potential Interactions
| Interacting Drug / Category | Effect | Clinical Significance |
|---|---|---|
| Live vaccines (e.g., MMR, varicella, BCG, yellow fever) | Risk of vaccine-strain infection due to immunosuppression from combination chemotherapy | Avoid during treatment and for several months after completing therapy |
| Antiemetics (5-HT3 antagonists, NK1 antagonists, corticosteroids) | No negative interaction; recommended as pre-medication | Routinely co-administered before each Vyloy infusion to prevent nausea and vomiting |
| Warfarin / Anticoagulants | Fluoropyrimidine chemotherapy (5-FU, capecitabine) can increase anticoagulant effect | Monitor INR closely; dose adjustment of anticoagulant may be required |
| Phenytoin | Fluoropyrimidines may increase phenytoin levels | Monitor phenytoin levels; dose adjustment may be necessary |
| Nephrotoxic agents (aminoglycosides, NSAIDs) | Combined with oxaliplatin, may increase risk of kidney toxicity | Use with caution; monitor renal function closely |
| Other immunosuppressive agents | Additive immunosuppression, increased infection risk | Monitor for signs of infection; consider prophylactic measures |
Because Vyloy is always given alongside fluoropyrimidine and/or platinum-based chemotherapy, it is essential to also review the drug interaction profiles of those agents. Your oncologist and pharmacist will check for interactions between all components of your treatment regimen and any other medications you are taking.
What Is the Correct Dosage of Vyloy?
Vyloy treatment is always administered in a hospital or clinic setting under the supervision of a physician experienced in the management of cancer patients. The medication is given as an intravenous (IV) infusion (drip) into a vein over a minimum of 2 hours. It must not be administered as an intravenous push or bolus injection.
Adults
The dose of Vyloy is calculated based on the patient’s body surface area (BSA), which is determined from height and weight. Your oncologist will determine the exact dose for each infusion cycle. The treatment schedule (every 2 weeks or every 3 weeks) depends on which chemotherapy combination your oncologist has selected:
With mFOLFOX6 Regimen (Every 2 Weeks)
When Vyloy is combined with mFOLFOX6 (oxaliplatin, leucovorin, and 5-fluorouracil), it is administered on Day 1 of each 14-day cycle. The infusion is given over at least 2 hours, followed by the chemotherapy agents.
With CAPOX Regimen (Every 3 Weeks)
When Vyloy is combined with CAPOX (capecitabine plus oxaliplatin), it is administered on Day 1 of each 21-day cycle. The infusion is given over at least 2 hours, followed by the chemotherapy agents. Capecitabine is then taken orally at home as directed.
Your oncologist will decide how many treatment cycles you will receive based on your response to therapy, disease progression, and tolerability. Treatment is generally continued as long as there is clinical benefit and the side effects remain manageable.
Children and Adolescents
Vyloy has not been studied in patients under 18 years of age. There is no relevant use of this medication in the pediatric population for the treatment of gastric or gastroesophageal junction adenocarcinoma.
Elderly Patients
No specific dose adjustment is required for elderly patients. However, older patients may be more susceptible to certain side effects, particularly nausea, vomiting, and myelosuppression from the combination chemotherapy. Your oncologist will carefully assess your overall health, kidney and liver function, and other medications before determining the most appropriate dose and regimen.
Missed Dose
If you miss a scheduled Vyloy infusion, contact your doctor or treatment team as soon as possible to reschedule. Do not stop treatment without discussing it with your oncologist. Stopping treatment prematurely may reduce the effectiveness of the medication against your cancer. Your doctor will determine the best time to resume your treatment schedule.
Overdose
Because Vyloy is administered by healthcare professionals in a supervised clinical setting, overdose is unlikely. In the event of an overdose, there is no specific antidote for zolbetuximab. Treatment would be supportive, focusing on managing any symptoms that arise, particularly severe nausea, vomiting, and infusion-related reactions. Your medical team will monitor you closely and provide appropriate supportive care.
Before each Vyloy infusion, you will receive anti-nausea medication (antiemetics) to help prevent the nausea and vomiting that commonly occur with this treatment. Your doctor may also prescribe additional medications to take at home to manage any delayed nausea. It is very important to take all pre-medications as directed.
What Are the Side Effects of Vyloy?
Like all medicines, Vyloy can cause side effects, although not everyone will experience them. Some side effects can be serious and require immediate medical attention. The side effects listed below reflect those observed in clinical trials when Vyloy was given in combination with chemotherapy. Some of the listed effects may also be attributable in part to the chemotherapy agents used alongside Vyloy.
Serious Side Effects
The following serious side effects have been reported with Vyloy. If you experience any of these, seek immediate medical attention:
- Hypersensitivity reactions (allergic reactions) including anaphylaxis – common (may affect up to 1 in 10 people). Symptoms include itchy, swollen pink or red areas on the skin (hives), persistent cough, breathing difficulties such as wheezing, or throat tightness with voice changes. Anaphylaxis is a severe, potentially life-threatening allergic reaction that requires emergency treatment.
- Infusion-related reactions – common (may affect up to 1 in 10 people). Symptoms may include nausea, vomiting, abdominal pain, excessive salivation, fever, chest discomfort, chills or rigors, back pain, cough, or high blood pressure.
- Severe nausea and vomiting – very common (may affect more than 1 in 10 people). While nausea and vomiting are expected side effects, they can sometimes become severe enough to require hospitalization, intravenous fluids, or dose modifications.
Side Effects by Frequency
Very Common
May affect more than 1 in 10 people
- Nausea
- Vomiting
- Decreased appetite
- Low white blood cell counts (leukopenia / neutropenia)
- Low albumin levels in the blood (hypoalbuminemia)
- Swelling of the lower legs and hands (peripheral edema)
- Weight loss
- Fever (pyrexia)
Common
May affect up to 1 in 10 people
- Indigestion (dyspepsia)
- Excessive salivation (salivary hypersecretion)
- High blood pressure (hypertension)
- Chills
- Hypersensitivity reactions (allergic reactions)
- Infusion-related reactions
- Anaphylactic reaction
The side effects listed above are those specifically attributed to or commonly observed with Vyloy treatment. When Vyloy is given in combination with chemotherapy, you may also experience additional side effects from the chemotherapy agents. These may include but are not limited to peripheral neuropathy (numbness or tingling in hands and feet), diarrhea, mouth sores, hair changes, fatigue, and low blood cell counts. Your oncologist will explain the complete side effect profile of your entire treatment regimen.
When to Seek Medical Help
Contact your doctor or healthcare team immediately if you experience any of the following during or after treatment with Vyloy:
- Signs of a severe allergic reaction: widespread rash or hives, swelling of the face or throat, difficulty breathing, wheezing, rapid heartbeat, or feeling faint
- Persistent or severe vomiting that prevents you from keeping down fluids or food
- Fever above 38°C (100.4°F), which may indicate an infection related to low white blood cell counts
- Unusual bruising or bleeding, which may indicate low platelet counts
- Severe abdominal pain, especially if accompanied by nausea and vomiting
Reporting suspected side effects after a medicine has been authorized is important. It allows ongoing monitoring of the benefit-risk balance of the medication. Healthcare professionals and patients are encouraged to report suspected adverse reactions to their national regulatory authority or through established pharmacovigilance reporting channels.
How Should Vyloy Be Stored?
The storage and handling of Vyloy are the responsibility of healthcare professionals at the hospital, clinic, or pharmacy where you receive treatment. The following storage conditions apply:
- Temperature: Store in a refrigerator at 2°C to 8°C (36°F to 46°F)
- Freezing: Do not freeze the product
- Light protection: Keep in the original packaging to protect from light
- Expiration: Do not use after the expiration date printed on the carton and vial label (EXP). The expiration date refers to the last day of the stated month
- Single use: Vyloy vials are for single use only. Any unused medication remaining in the vial after dose preparation must be discarded and not saved for later use
Keep this medicine out of the sight and reach of children. Unused medicine and waste should be disposed of in accordance with local regulations for cytotoxic (anticancer) medications.
What Does Vyloy Contain?
Active Ingredient
The active substance in Vyloy is zolbetuximab, a chimeric IgG1 monoclonal antibody produced using recombinant DNA technology. It is available in two vial sizes:
- 100 mg vial: Contains 100 mg of zolbetuximab as a lyophilized (freeze-dried) powder for concentrate for solution for infusion
- 300 mg vial: Contains 300 mg of zolbetuximab as a lyophilized powder for concentrate for solution for infusion
After reconstitution with sterile water for injection, each milliliter of solution contains 20 mg of zolbetuximab.
Other Ingredients (Excipients)
- Arginine
- Phosphoric acid (E 338)
- Sucrose
- Polysorbate 80 (E 433)
Appearance and Packaging
Vyloy powder for concentrate for solution for infusion is a white to off-white lyophilized (freeze-dried) powder. It is supplied in glass vials in cartons containing either 1 or 3 vials. Not all pack sizes may be available in all countries.
Marketing Authorization Holder and Manufacturer
Vyloy is manufactured by Astellas Ireland Co. Limited (Killorglin, Co Kerry, Ireland) and marketed by Astellas Pharma Europe B.V. (Sylviusweg 62, 2333 BE Leiden, Netherlands). For further information about this medicine, contact your local Astellas Pharma representative or consult the European Medicines Agency (EMA) website.
Frequently Asked Questions About Vyloy
Claudin 18.2 (CLDN18.2) is a protein that forms part of tight junctions between cells, helping to hold cells together. It is predominantly found in normal stomach lining cells. In many gastric cancers, CLDN18.2 becomes exposed on the cell surface due to disruption of normal tissue architecture, making it accessible to antibodies like zolbetuximab. Testing for CLDN18.2 expression on your tumor is required before starting Vyloy, because the drug works specifically by binding to this protein to trigger immune-mediated cancer cell destruction. Approximately 38% of gastric and gastroesophageal junction cancers that are HER2-negative are also CLDN18.2-positive.
Each Vyloy infusion is administered over a minimum of 2 hours. Including the pre-medication with antiemetics (anti-nausea drugs) and the post-infusion observation period, you should expect to spend several hours at the treatment center for each session. The chemotherapy agents are typically given after the Vyloy infusion is complete. Your healthcare team will explain the full schedule for each treatment visit.
Vyloy was approved based on results from two pivotal phase III clinical trials: SPOTLIGHT and GLOW. The SPOTLIGHT trial evaluated zolbetuximab in combination with mFOLFOX6 chemotherapy, while the GLOW trial evaluated zolbetuximab with CAPOX chemotherapy. Both trials enrolled patients with CLDN18.2-positive, HER2-negative, locally advanced unresectable or metastatic gastric or GEJ adenocarcinoma. Both trials demonstrated statistically significant improvements in progression-free survival (PFS) and overall survival (OS) when Vyloy was added to chemotherapy compared with placebo plus chemotherapy.
Zolbetuximab is a monoclonal antibody that is cleared through intracellular catabolism rather than hepatic or renal metabolism, so mild to moderate kidney or liver impairment is not expected to significantly affect its clearance. However, the companion chemotherapy agents used with Vyloy (fluoropyrimidines and platinum compounds) are significantly affected by kidney and liver function. Your oncologist will carefully evaluate your kidney and liver function before starting treatment and may adjust the chemotherapy doses accordingly. Regular blood tests will be performed throughout treatment to monitor these organ functions.
If you experience a severe allergic reaction (anaphylaxis) during a Vyloy infusion, your healthcare team is trained to respond immediately. The infusion will be stopped right away, and you will receive emergency treatment which may include epinephrine (adrenaline), corticosteroids, antihistamines, and supportive care. You will be closely monitored until the reaction has fully resolved. If you have had a severe allergic reaction to Vyloy, treatment with this medication will typically be permanently discontinued to prevent recurrence. Milder reactions may be managed with pre-medication and slower infusion rates for subsequent doses, at your doctor’s discretion.
Vyloy (zolbetuximab) is a targeted monoclonal antibody, which is a form of immunotherapy in the broader sense. However, it works differently from checkpoint inhibitors (such as pembrolizumab or nivolumab) that are commonly associated with the term “immunotherapy” in cancer treatment. While checkpoint inhibitors release the brakes on the immune system to attack cancer cells more broadly, zolbetuximab specifically targets the CLDN18.2 protein on cancer cells and recruits immune effector mechanisms (ADCC and CDC) to destroy those specific cells. It is more accurately described as a targeted antibody therapy.
References
- European Medicines Agency (EMA). Vyloy (zolbetuximab) – Summary of Product Characteristics. 2025. Available at: www.ema.europa.eu
- U.S. Food and Drug Administration (FDA). Vyloy (zolbetuximab-clhb) – Prescribing Information. 2024.
- 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.
- Shah MA, Shitara K, Ajani JA, et al. Zolbetuximab plus CAPOX in CLDN18.2-positive, HER2-negative, untreated, locally advanced unresectable or metastatic gastric or gastro-oesophageal junction adenocarcinoma (GLOW): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet. 2023;402(10403):1007–1019.
- European Society for Medical Oncology (ESMO). Clinical Practice Guidelines: Gastric Cancer. 2024. Available at: www.esmo.org
- National Comprehensive Cancer Network (NCCN). Clinical Practice Guidelines in Oncology: Gastric Cancer. Version 2.2025.
- World Health Organization (WHO). Cancer Fact Sheets: Stomach Cancer. 2024. Available at: www.who.int
- Sahin U, Türeci Ö, Manikhas G, et al. FAST: a randomised phase II study of zolbetuximab (IMAB362) plus EOX versus EOX alone for first-line treatment of advanced CLDN18.2-positive gastric and gastro-oesophageal adenocarcinoma. Ann Oncol. 2021;32(5):609–619.
- Lordick F, Carneiro F, Cascinu S, et al. Gastric cancer: ESMO Clinical Practice Guideline for diagnosis, treatment and follow-up. Ann Oncol. 2022;33(10):1005–1020.
Editorial Team
Medical Content
iMedic Medical Editorial Team – Specialists in Oncology and Clinical Pharmacology
Medical Review
iMedic Medical Review Board – Independent panel following WHO, EMA, FDA, and ESMO guidelines
Evidence Standard
Level 1A – Based on systematic reviews and randomized controlled trials (GRADE framework)
Editorial Independence
No commercial funding or pharmaceutical industry sponsorship. All content is editorially independent.
Last reviewed: | Next review scheduled: