Zolbetuximab-clzb, a humanized immunoglobulin G1 (IgG1), Claudin (CLDN) 18.2-directed cytolytic antibody, is an antineoplastic agent.1, 2, 3
Gastric Cancer and Gastroesophageal Junction Cancer
Zolbetuximab-clzb, in combination with fluoropyrimidine- and platinum-containing chemotherapy, is used for the first-line treatment of adult patients with locally advanced unresectable or metastatic human epithelial receptor 2 (HER2)-negative gastric and gastroesophageal junction (GEJ) cancer whose tumors are CLDN18.2-positive, as determined by an FDA-approved test.1, 2, 3 Information on FDA-approved tests for the detection of CLDN18.2 is available at: [Web].1
Zolbetuximab-clzb has been designated an orphan drug by FDA for the treatment of gastric cancer.4
First-line Treatment of Locally Advanced Unresectable or Metastatic Gastric and GEJ Cancer
The safety and efficacy of zolbetuximab-clzb as first-line treatment of locally advanced unresectable or metastatic HER2-negative, CLDN18.2-positive gastric and GEJ cancer were principally established in 2 phase 3, double-blind, randomized, placebo-controlled trials (SPOTLIGHT and GLOW) evaluating zolbetuximab-clzb versus placebo, in combination with mFOLFOX6 (oxaliplatin, leucovorin, and fluorouracil) and CAPOX (capecitabine and oxaliplatin), respectively.1, 2, 3
Both trials (SPOTLIGHT and GLOW) included adults with locally advanced unresectable or metastatic HER2-negative, CLDN18.2-positive gastric or GEJ adenocarcinoma.1, 2, 3 CLDN18.2 positivity was defined as ≥75% of tumor cells demonstrating moderate-strong membranous CLDN18 staining, and was determined by immunohistochemistry on gastric or GEJ tumor tissue specimens using the VENTANA CLDN18 (43-14A) RxDx Assay, performed in a central laboratory.1, 2, 3 Patients were excluded if they had complete or partial gastric outlet syndrome or a history of central nervous system (CNS) metastases.1, 2, 3
In SPOTLIGHT, patients were randomized 1:1 (stratified by region, number of organs with metastases, and previous gastrectomy) to receive zolbetuximab-clzb in combination with mFOLFOX, or placebo in combination with mFOLFOX6.1, 2 Zolbetuximab-clzb was administered as an IV infusion at an initial dose of 800 mg/m2 (Day 1, Cycle 1) followed by subsequent doses of 600 mg/m2(Day 22, Cycle 1, and Days 1 and 22 of subsequent cycles) in 42-day cycles.1, 2 Patients in the zolbetuximab-clzb and placebo cohorts received up to 12 treatments of mFOLFOX6 (folinic acid [leucovorin] 400 mg/m2; 5-fluorouracil 400 mg/m2 given as a bolus followed by 2400 mg/m2in a 46-48 hour infusion; oxaliplatin 85 mg/m2) administered on Days 1, 15, and 29 of 42-day cycles.1, 2 After 12 treatments, patients were allowed to continue treatment with zolbetuximab-clzb (zolbetuximab-clzb cohort only), 5-fluorouracil, and leucovorin until disease progression or toxicity, start of another anticancer treatment, or other discontinuation criteria were met.1, 2 Tumors were assessed every 9 weeks until Week 54, followed by every 12 weeks thereafter.1, 2 The primary efficacy endpoint was progression free survival (PFS) as assessed by an independent review committee (IRC) per RECIST 1.1.1, 2 Secondary outcomes included overall survival (OS), objective response rate (ORR; defined as patients achieving complete response or partial response), and duration of response (DOR), as assessed by IRC per RECIST 1.1.1, 2
A total of 565 patients were randomized (283 to zolbetuximab-clzb, 282 to placebo).1, 2 The median age was 61 years (20-86 years); the majority were male (62%) and White (48%) with an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 (98%).1, 2 More patients had gastric cancer (76%) than GEJ (24%), and most had metastatic disease (84%); 29% had undergone prior gastrectomy.1, 2
Patients treated with zolbetuximab-clzb plus mFOLFOX6 experienced prolonged median PFS (10.6 months) compared to patients treated with placebo plus mFOLFOX6 (8.7 months).1, 2 Median OS was 18.2 months and 15.5 months in patients treated with zolbetuximab-clzb plus mFOLFOX6 and placebo plus mFOLFOX6, respectively.1, 2 Objective response rate was 40.3% in zolbetuximab-clzb-treated patients compared to 39.7% in placebo.1, 7 In patients who achieved a response (complete or partial response), median DOR was 10.3 months and 10.5 months, respectively, in zolbetuximab-treated patients compared to placebo-treated patients.1, 7
In GLOW, patients were randomized 1:1 (stratified by region, number of organs with metastases, and previous gastrectomy) to receive zolbetuximab-clzb in combination with CAPOX, or placebo in combination with CAPOX.1, 3 Zolbetuximab-clzb was administered as an IV infusion at an initial dose of 800 mg/m2 (Day 1, Cycle 1) followed by subsequent doses of 600 mg/m2 (Day 1 of subsequent cycles) in 21-day cycles.1, 3 CAPOX (oral capecitabine 1000 mg/m2 twice daily on Days 1, 14; IV oxaliplatin 130 mg/m2 on Day 1) was administered for eight 21-day cycles.1, 3 After 8 cycles, patients continued treatment with zolbetuximab-clzb or placebo, plus, at the investigator's discretion, capecitabine, until disease progression, unacceptable toxicity, initiation of another anti-cancer treatment, or discontinuation criteria were met.1, 3 Tumors were assessed every 9 weeks until Week 54, followed by every 12 weeks thereafter.1, 3
The primary efficacy endpoint was PFS as assessed by IRC per RECIST 1.1.1, 3 Secondary outcomes included OS, ORR (defined as patients achieving complete response or partial response), and DOR, as assessed by IRC per RECIST 1.1.1, 3
A total of 507 patients were randomized (254 to zolbetuximab-clzb, 253 to placebo).1, 3 The median age was 60 years (21-83 years); the majority were male (62%) and Asian (62%) with an ECOG performance status of 0 or 1 (99%).1, 3 More patients had gastric cancer (84%) than GEJ (16%), and most had metastatic disease (88%); 27% had undergone prior gastrectomy.1, 3
Patients treated with zolbetuximab-clzb and CAPOX experienced prolonged median PFS (8.2 months) compared to patients treated with placebo and CAPOX (6.8 months).1, 3 Median OS was 14.4 months and 12.2 months in patients treated with zolbetuximab-clzb with CAPOX and placebo with CAPOX, respectively.1, 3 Objective response rate was 32.3% in zolbetuximab-clzb-treated patients compared to 31.2% in placebo.1, 7 In patients who achieved a response (complete or partial response), median DOR was 8.3 months and 6.2 months, respectively, in zolbetuximab-treated patients compared to placebo-treated patients.1, 7
Administer zolbetuximab-clzb via IV infusion in a dedicated line with a low protein-binding 0.2-micron in-line filter.1
If administered on the same day as fluoropyrimidine- and platinum-containing chemotherapy, administer zolbetuximab-clzb first.1
Zolbetuximab-clzb is available as 100 and 300 mg single-dose vials of white to off-white lyophilized powder that must be reconstituted and diluted prior to IV infusion.1 Do not administer via rapid IV bolus injection.1
Do not administer zolbetuximab-clzb in the same IV line with other medications.1
Store vials of zolbetuximab-clzb refrigerated at 2-8°C in original carton.1 Do not freeze.1
Zolbetuximab-clzb is compatible with 0.9% sodium chloride injection.1
Determine the number of zolbetuximab-clzb vials needed to obtain the appropriate dose according to the patient's body surface area.1
Reconstitute each 100 mg and 300 mg vial with 5 mL and 15 mL of sterile water for injection, respectively.1 Direct the stream toward the inside wall of the vial; do not inject directly onto the lyophilized powder.1 Swirl the vial gently until completely dissolved; do not shake.1 The concentration of each reconstituted vial should be 20 mg/mL.1
Inspect the reconstituted solution for particulate matter and discoloration.1 The reconstituted solution should be a colorless to light yellow, clear to slightly opalescent solution with no visible particles.1 Discard if any particulate matter or discoloration is observed.1
The reconstituted solution should be used immediately, or stored at room temperature (15-30°C) for ≤5 hours.1
Following reconstitution, withdraw the necessary volume for the calculated zolbetuximab-clzb dose from each vial.1 Slowly add the necessary dose volume to a polyethylene (PE), polypropylene (PP), polyvinyl chloride (PVC) [with either Di(2-ethylhexyl) phthalate (DEHP) or, Trioctyl trimellitate (TOTM) plasticizers], ethylene propylene copolymer, ethylene-vinyl acetate (EVA) copolymer, PP and styrene-ethylene-butylene-styrene copolymer infusion bag containing 0.9% sodium chloride injection.1 The final concentration should be 5 mg/mL.1 Discard any unused reconstituted solution remaining in the vials.1
Gently invert the infusion bag to mix.1 Do not shake.1
The infusion solution must be a clear, colorless solution with no visible particles.1 Do not use if the solution is discolored or particles are observed.1
Store prepared zolbetuximab-clzb solution at room temperature (15-30°C) for ≤6 hours or in the refrigerator (2-8°C) for ≤16 hours, including time from reconstitution to completion of IV infusion.1
Zolbetuximab-clzb is administered via IV infusion as described in Table 1.1 The infusion rate may be gradually increased as tolerated after the first 30-60 minutes to the subsequent infusion rate.1
Temporary interruption or infusion rate reduction may be necessary for patients who experience infusion-related reactions (IRRs).1
Zolbetuximab-clzb Dose | Initial Infusion Rate (first 30-60 minutes) | Subsequent Infusion Rate |
|---|---|---|
First Dose: 800 mg/m2 | 100 mg/m2 per hour | 200-265 mg/m2 per hour |
Subsequent Doses: 600 mg/m2 every 3 weeks or 400 mg/m2 every 2 weeks | 75 mg/m2 per hour or 50 mg/m2 per hour | 150-265 mg/m2 per hour or 100-200 mg/m2 per hour |
Gastric Cancer and Gastroesophageal Junction Cancer
For the first-line treatment of locally advanced unresectable or metastatic (HER2)-negative, CLDN18.2-positive gastric and gastroesophageal junction (GEJ) cancer, the recommended adult initial dose of zolbetuximab-clzb is 800 mg/m2 IV followed by subsequent doses of either 600 mg/m2 IV every 3 weeks or 400 mg/m2 IV every 2 weeks, in combination with fluoropyrimidine- and platinum-containing chemotherapy.1 Therapy should be continued until disease progression or unacceptable toxicity occurs.1
Dosage Modification for Toxicity
If adverse events occur during zolbetuximab-clzb therapy, reduction of the infusion rate, temporary interruption of the infusion, withholding the drug, and/or discontinuance of the drug may be necessary.1 Dosage reduction is not recommended.1
Adverse event severity is graded per National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) version 5.1
Hypersensitivity or Infusion-Related Reactions
If Grade 2 reactions occurs, interrupt the infusion until Grade ≤1, then resume at a reduced infusion rate for the remaining infusion.1 For subsequent infusions, premedicate and administer per the infusion rates in Table 1.1
If Grade 3 or 4 reactions or anaphylaxis occurs, immediately stop the zolbetuximab-clzb and permanently discontinue.1
If Grade 3 infusion-related nausea and vomiting occurs, interrupt the infusion until Grade ≤1, then resume at a reduced infusion rate for the remaining infusion.1 For subsequent infusions, premedicate and administer per the infusion rates in Table 1.1
The manufacturer makes no specific recommendations for patients with hepatic impairment.1
The manufacturer makes no specific recommendations for patients with renal impairment.1
The manufacturer makes no specific recommendations for geriatric patients.1
Hypersensitivity reactions, including serious anaphylaxis reactions, and serious and fatal infusion-related reactions (IRRs) have been reported in clinical studies with zolbetuximab-clzb.1 In a pooled safety analysis, any grade hypersensitivity reactions, including anaphylactic reactions, occurred in 18% of patients treated with zolbetuximab-clzb concomitantly with mFOLFOX6 or CAPOX.1, 2, 3 Severe (Grade 3 or 4) hypersensitivity reactions, including anaphylaxis, occurred in 2% of patients.1 Seven (1.3%) patients permanently discontinued zolbetuximab-clzb for hypersensitivity reactions, including 2 (0.4%) patients who permanently discontinued zolbetuximab-clzb due to anaphylaxis.1 Dose interruption was required in 17 patients (3.2%); 3 patients (0.6%) required infusion rate reduction due to hypersensitivity reactions.1
Any grade IRRs occurred in 3.2% of patients treated with zolbetuximab-clzb concomitantly with mFOLFOX6 or CAPOX; severe (Grade 3) IRRs occurred in 2 (0.4%) patients.1 Two (0.4%) patients permanently discontinued zolbetuximab-clzb due to IRRs.1 Dose interruption was required in 7 (1.3%) patients; 2 (0.4%) patients required infusion rate reduction due to IRRs.1
Monitor patients for signs and symptoms of hypersensitivity reactions that are highly suggestive of anaphylaxis (urticaria, repetitive cough, wheeze, throat tightness/change in voice) during zolbetuximab-clzb infusion and for ≥2 hours after completion.1
Monitor patients for signs and symptoms of IRRs including nausea, vomiting, abdominal pain, salivary hypersecretion, pyrexia, chest discomfort, chills, back pain, cough, and hypertension.1
If a severe or life-threatening hypersensitivity or IRR occurs, discontinue zolbetuximab-clzb permanently, treat symptoms according to standard medical care, and monitor until symptoms resolve.1
For any Grade 2 hypersensitivity reaction or IRR, temporarily interrupt the zolbetuximab-clzb infusion until signs and symptoms resolve to Grade ≤1, then resume at a reduced infusion rate for the remaining infusion.1 For subsequent infusions, premedicate the patient with antihistamines, administer per the infusion rates in Table 1, and closely monitor the patient for signs and symptoms of a hypersensitivity reaction.1 The infusion rate may be gradually increased as tolerated.1
Zolbetuximab-clzb is emetogenic.1 Nausea and vomiting occurred more often during the first cycle of treatment.1 In SPOTLIGHT, all grade nausea or vomiting occurred in 82% and 67%, respectively, of patients treated with zolbetuximab-clzb in combination with mFOLFOX6 compared to 61% and 36%, respectively, of patients treated with placebo plus mFOLFOX6.1, 2 In GLOW, all grade nausea or vomiting occurred in 69% and 66%, respectively, of patients treated with zolbetuximab-clzb in combination with CAPOX compared to 50% and 31%, respectively, of patients treated with placebo plus CAPOX.1, 3 Severe (Grade 3) nausea occurred in 16% and 9% of patients treated with zolbetuximab-clzb plus mFOLFOX6 or CAPOX, respectively, compared to 6% and 3% of patients treated with placebo plus mFOLFOX6 or CAPOX, respectively.1 Severe (Grade 3) vomiting occurred in 16% and 12% of patients treated with zolbetuximab-clzb plus mFOLFOX6 or CAPOX, respectively, compared to 6% and 4% of patients treated with placebo plus mFOLFOX6 or CAPOX, respectively.1 Nausea led to permanent discontinuation of zolbetuximab-clzb in combination with mFOLFOX6 or CAPOX in 18 patients (3.4%) and dose interruption in 147 patients (28%).1 Vomiting led to permanent discontinuation of zolbetuximab-clzb in combination with mFOLXFOX6 or CAPOX in 20 patients (3.8%) and dose interruption in 150 patients (28%).1
Premedicate with antiemetics prior to each zolbetuximab-clzb infusion.1 Manage patients during and after infusion with antiemetics or fluid replacement.1
Temporary interruption or permanent discontinuance of zolbetuximab-clzb may be necessary based on severity of nausea and/or vomiting.1
There are no human data on zolbetuximab-clzb use in pregnant women to inform any drug-associated risk.1 In animal studies, embryo-fetal toxicity was not observed in pregnant mice following administration of zolbetuximab-clzb at doses ≤300 mg/kg (approximately 1.9 times the recommended clinical dose).1 Zolbetuximab-clzb crosses the placental barrier; in mice, higher fetal serum concentrations were observed on Day 18 of gestation than maternal serum concentrations on Day 16 of gestation.1
It is not known whether zolbetuximab-clzb is distributed into human milk.1 Effects of the drug on breastfed infants or milk production are also not known.1 However, antibodies may be excreted in human milk, leading to potential adverse reactions in a breastfed child.1
Advise lactating women not to breastfeed during zolbetuximab-clzb treatment and for 8 months after the last dose.1
Females and Males of Reproductive Potential
Zolbetuximab-clzb is used in combination with fluoropyrimidine- or platinum-containing chemotherapy.1 Refer to the full prescribing information of fluoropyrimidine- and platinum-containing chemotherapy products for pregnancy testing, contraception, and infertility information.1
Safety and efficacy of zolbetuximab-clzb have not been established in pediatric patients <18 years of age.1
In clinical studies, 34% of patients were >65 years of a 5% were >75 years of age.1 No overall differences in safety or efficacy were observed between geriatric patients (≥65 years of age) and younger adults (<65 years of age).1
Mild hepatic impairment (total bilirubin ≤ the upper limit of normal [ULN] and AST >ULN, or total bilirubin >1-1.5 times ULN and any AST) does not have a clinically important effect on the pharmacokinetics of zolbetuximab-clzb; however, the effects of moderate to severe hepatic impairment have not been studied.1
Mild to moderate renal impairment (creatinine clearance ≥30 to <90 mL/minute) does not have a clinically important effect on the pharmacokinetics of zolbetuximab-clzb; however, the effects of severe renal impairment have not been studied.1
The most common adverse reactions (incidence ≥15%) reported with zolbetuximab-clzb in combination with mFOLFOX6 or CAPOX in clinical studies were nausea, vomiting, fatigue, decreased appetite, diarrhea, peripheral sensory neuropathy, abdominal pain, constipation, decreased weight, hypersensitivity reactions, and pyrexia.1
The most common laboratory abnormalities (incidence ≥15%) reported with zolbetuximab-clzb in combination with mFOLFOX6 or CAPOX in clinical studies were decreased neutrophil count, decreased leukocyte count, decreased albumin, increased creatinine, decreased hemoglobin, increased glucose, decreased lymphocyte count, increased AST, decreased platelets, increased alkaline phosphatase, increased ALT, decreased glucose, decreased sodium, increased phosphate, decreased potassium, and decreased magnesium.1
Zolbetuximab-clzb, an IgG1, CLDN18.2-directed cytolytic antibody, is an antineoplastic agent.1 CLDN18.2 is a tight junction protein normally expressed in gastric mucosa cells and retained in most gastric and GEJ cancers as the dominant isoform expressed in both normal and malignant gastric cells.1, 2, 3 In malignant transformation, it is thought that CLDN18.2 becomes exposed on the surface of gastric and GEJ cells, thus improving antibody accessibility.2, 3 Zolbetuximab-clzb binds to CLDN18.2, mediating cell death of CLDN18.2-positive gastric and GEJ adenocarcinoma cells via antibody-dependent cellular cytotoxicity and complement-dependent cytotoxicity.1, 2, 3 In combination with fluoropyrimidine- and platinum-containing chemotherapy, zolbetuximab-clzb demonstrated increased antitumor activity in CLDN18.2-expressing mouse tumor models compared to zolbetuximab-clzb or chemotherapy alone.1
Zolbetuximab-clzb demonstrates dose-proportional pharmacokinetics.1 Steady state is achieved by approximately 18 weeks following the first dose of 800 mg/m2 and subsequent doses of 600 mg/m2 every 3 weeks.1 Zolbetuximab-clzb is expected to be catabolized into small peptides and amino acids.1 The mean plasma half-life of zolbetuximab-clzb is 41 days.1 Age (22-83 years), race (White, Asian, Black), mild to moderate renal impairment (creatinine clearance ≥30 mL/minute to <90 mL/minute), or mild hepatic impairment (total bilirubin ≤ ULN and AST > ULN, or total bilirubin >1 to 1.5 times the ULN and any AST) do not have clinically important effects on the pharmacokinetics of zolbetuximab-clzb.1
Additional Information
The American Society of Health-System Pharmacists, Inc. represents that the information provided in the accompanying monograph was formulated with a reasonable standard of care, and in conformity with professional standards in the field. Readers are advised that decisions regarding use of drugs are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and that the information contained in the monograph is provided for informational purposes only. The manufacturer's labeling should be consulted for more detailed information. The American Society of Health-System Pharmacists, Inc. does not endorse or recommend the use of any drug. The information contained in the monograph is not a substitute for medical care. For further information on the handling of antineoplastic agents, see the ASHP Guidelines on Handling Hazardous Drugs at [Web].
Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.
Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.
Zolbetuximab-clzb is obtained through specialty pharmacy distributors.8 Contact the manufacturer or consult the zolbetuximab-clzb website [Web] for specific availability information.8
Routes | Dosage Forms | Strengths | Brand Names | Manufacturer |
|---|---|---|---|---|
Parenteral | For injection, for IV infusion | 100 mg | Vyloy® | Astellas Pharma |
300 mg | Vyloy® | Astellas Pharma |
AHFS® Drug Information. © Copyright, 1959-2026, Selected Revisions June 10, 2026. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, MD 20814.
Only references cited for selected revisions after 1984 are available electronically.
1. Astellas Pharma US, Inc. VYLOY® (zolbetuximab-clzb) injection prescribing information. Northbrook, IL; 2025 June.
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 gatro-oesophageal junction adenocarcinoma (SPOTLIGHT): a multicentre, randomised, double-blind, phase 3 trial. Lancet. 2023;401(10389):1655-1668. doi:10.1016/S0140-6736(23)00620-7.
3. 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.
4. Food and Drug Administration. Search Orphan Drug Designations and Approvals. Silver Springs, MD. From FDA website. Accessed 2026 Feb 22.
7. US Food and Drug Administration. Center for Drug Evaluation and Research. Application 761365Orig1s000. Multi-discipline review. October 2024. From FDA website.
8. Vyloy Access and Resources. Accessed 7 March 2026. http://www.vyloyhcp.com/access-and-resources.