WARNINGS AND PRECAUTIONS SECTION.

5 WARNINGS AND PRECAUTIONS oHypersensitivity reactions including serious anaphylaxis reactions and serious and fatal infusion-related reactions have occurred. Monitor patients during and for at least hours after infusion with VYLOY. Interrupt, slow the rate of infusion or permanently discontinue VYLOY based on severity and type of reaction. Premedicate with antihistamines for subsequent infusions after hypersensitivity reaction. (2.4, 5.1)oSevere nausea and vomiting: Premedicate patients with antiemetics prior to each infusion. Interrupt or permanently discontinue VYLOY based on the severity of the nausea and/or vomiting. Manage patients during and after infusion with antiemetics or fluid replacement. (2.4, 5.2). oHypersensitivity reactions including serious anaphylaxis reactions and serious and fatal infusion-related reactions have occurred. Monitor patients during and for at least hours after infusion with VYLOY. Interrupt, slow the rate of infusion or permanently discontinue VYLOY based on severity and type of reaction. Premedicate with antihistamines for subsequent infusions after hypersensitivity reaction. (2.4, 5.1). oSevere nausea and vomiting: Premedicate patients with antiemetics prior to each infusion. Interrupt or permanently discontinue VYLOY based on the severity of the nausea and/or vomiting. Manage patients during and after infusion with antiemetics or fluid replacement. (2.4, 5.2). 5.1 Hypersensitivity reactions, including anaphylaxis reactions, and infusion related reactions Hypersensitivity reactions, including serious anaphylaxis reactions, and serious and fatal infusion-related reactions (IRR) have been reported in clinical studies when VYLOY has been administered. Any grade hypersensitivity reactions, including anaphylactic reactions, occurring with VYLOY in combination with mFOLFOX6 or CAPOX was 18%. Severe (Grade or 4) hypersensitivity reactions, including anaphylactic reactions, occurred in 2% of patients. Seven patients (1.3%) permanently discontinued VYLOY for hypersensitivity reactions, including two patients (0.4%) who permanently discontinued VYLOY due to anaphylactic reactions. Seventeen (3.2%) patients required dose interruption, and three patients (0.6%) required infusion rate reduction due to hypersensitivity reactions.All grade IRRs occurred in 3.2% in patients administered VYLOY in combination with mFOLFOX6 or CAPOX. Severe (Grade 3) IRRs occurred in (0.4%) patients who received VYLOY. An IRR led to permanent discontinuation of VYLOY in (0.4%) patients and dose interruption in (1.3%) patients. The infusion rate was reduced for VYLOY for (0.4%) patients due to an IRR. Monitor patients during infusion with VYLOY and for hours after completion of infusion or longer if clinically indicated, for hypersensitivity reactions with symptoms and signs that are highly suggestive of anaphylaxis (urticaria, repetitive cough, wheeze and throat tightness/change in voice). Monitor patients for signs and symptoms of IRRs including nausea, vomiting, abdominal pain, salivary hypersecretion, pyrexia, chest discomfort, chills, back pain, cough and hypertension.If severe or life-threatening hypersensitivity or IRR reaction occurs, discontinue VYLOY permanently, treat symptoms according to standard medical care, and monitor until symptoms resolve. For any Grade hypersensitivity or IRR, interrupt the VYLOY infusion until Grade <=1, then resume at reduced infusion rate for the remaining infusion. Premedicate the patient with antihistamines for the subsequent infusions, administer per the infusion rates in Table and closely monitor the patient for symptoms and signs of hypersensitivity reaction. The infusion rate may be gradually increased as tolerated [see Dosage and Administration (2.4)].. 5.2 Severe Nausea and Vomiting VYLOY is emetogenic. Nausea and vomiting occurred more often during the first cycle of treatment. All grade nausea and vomiting occurred in 82% and 67%, respectively, of patients treated with VYLOY in combination with mFOLFOX6 and 69% and 66% in combination with CAPOX, respectively. Severe (Grade 3) nausea occurred in 16% and 9% of patients treated with VYLOY in combination with mFOLFOX6 or CAPOX respectively. Severe (Grade 3) vomiting occurred in 16% and 12% of patients treated with VYLOY in combination with mFOLFOX6 or CAPOX. Nausea led to permanent discontinuation of VYLOY in combination with mFOLFOX6 or CAPOX in 18 (3.4%) patients and dose interruption in 147 (28%) patients. Vomiting led to permanent discontinuation of VYLOY in combination with mFOLFOX6 or CAPOX in 20 (3.8%) patients and dose interruption in 150 (28%) patients. Pretreat with antiemetics prior to each infusion of VYLOY [see Dosage and Administration (2.2)]. Manage patients during and after infusion with antiemetics or fluid replacement.Interrupt the infusion, or permanently discontinue VYLOY based on severity [see Dosage and Administration (2.4)].

SPL UNCLASSIFIED SECTION.

2.1 Patient Selection Select adult patients with locally advanced unresectable or metastatic HER2-negative gastric or GEJ adenocarcinoma whose tumors are CLDN18.2 positive (defined as >=75% of tumor cells demonstrating moderate to strong membranous CLDN18 immunohistochemical staining) for treatment with VYLOY in combination with fluoropyrimidine- and platinum-containing chemotherapy using an FDA-approved test [see Clinical Studies (14)]. Information on FDA-approved tests for the detection of CLDN18.2 is available at https://www.fda.gov/CompanionDiagnostics.

USE IN SPECIFIC POPULATIONS SECTION.

8 USE IN SPECIFIC POPULATIONS Lactation: Advise not to breastfeed. (8.2) 8.1 Pregnancy Risk SummaryThere are no data with VYLOY use in pregnant women to inform any drug-associated risks. Embryo-fetal toxicity was not observed in pregnant mice intravenously administered zolbetuximab-clzb [see Data]. VYLOY should only be given to pregnant woman if the benefit outweighs the potential risk.The background risk of major birth defects and miscarriage for the indicated population is unknown. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2%-4% and 15%-20%, respectively.DataAnimal DataIn an embryo-fetal development toxicity study, zolbetuximab-clzb was intravenously administered to pregnant mice during the period of organogenesis and did not result in embryo-fetal toxicity at doses up to 300 mg/kg (approximately 1.9 times the recommended clinical dose based on AUC). Zolbetuximab-clzb crossed the placental barrier resulting in higher fetal serum concentrations on Day 18 of gestation than maternal serum concentrations on Day 16 of gestation. 8.2 Lactation Risk SummaryThere are no data on the presence of zolbetuximab-clzb in human milk, the effects on the breastfed child, or the effects on milk production. Because antibodies may be excreted in human milk and because of the potential for adverse reactions in breastfed child, advise lactating woman not to breastfeed during treatment with VYLOY and for months after the last dose.. 8.3 Females and Males of Reproductive Potential VYLOY is used in combination with fluoropyrimidine- or platinum-containing chemotherapy. Refer to the Full Prescribing Information of fluoropyrimidine- and platinum-containing chemotherapy products for pregnancy testing, contraception, and infertility information. 8.4 Pediatric Use The safety and effectiveness of VYLOY in pediatric patients have not been established.. 8.5 Geriatric Use Of the 533 patients in clinical studies of VYLOY in combination with mFOLFOX6 or CAPOX, 34% (n=179) were over 65 years, and 5% were over 75 years (n=28) [see Clinical Studies (14)]. No overall differences in safety or effectiveness were observed between patients aged 65 years or older and younger patients.

DESCRIPTION SECTION.

11 DESCRIPTION Zolbetuximab-clzb is chimeric (mouse/human) antibody composed of variable regions derived from mouse anti-human claudin-18 isoform monoclonal antibody and constant regions derived from human IgG1. The molecular weight is approximately 147 kDa. VYLOY (zolbetuximab-clzb) for injection is provided as sterile, preservative-free, white to off-white lyophilized powder in single-dose vials for intravenous use. VYLOY is supplied as 100 mg or 300 mg per vial and requires reconstitution with Sterile Water for Injection, USP, (5 mL or 15 mL) resulting in clear to slightly opalescent, colorless to slightly yellow solution with final concentration of 20 mg/mL. Each mL of reconstituted solution contains 20 mg of zolbetuximab-clzb, arginine (23.24 mg), polysorbate 80 (0.21 mg), sucrose (51.30 mg), and phosphoric acid to adjust pH to 6.0.

DOSAGE & ADMINISTRATION SECTION.

2 DOSAGE AND ADMINISTRATION oAdminister by intravenous infusion only. Do not administer VYLOY as an intravenous push or bolus. (2.6)oThe recommended first dose of VYLOY is 800 mg/m2 followed by 600 mg/m2 every weeks or 400 mg/m2 every weeks. (2.3). oAdminister by intravenous infusion only. Do not administer VYLOY as an intravenous push or bolus. (2.6). oThe recommended first dose of VYLOY is 800 mg/m2 followed by 600 mg/m2 every weeks or 400 mg/m2 every weeks. (2.3). 2.1 Patient Selection Select adult patients with locally advanced unresectable or metastatic HER2-negative gastric or GEJ adenocarcinoma whose tumors are CLDN18.2 positive (defined as >=75% of tumor cells demonstrating moderate to strong membranous CLDN18 immunohistochemical staining) for treatment with VYLOY in combination with fluoropyrimidine- and platinum-containing chemotherapy using an FDA-approved test [see Clinical Studies (14)]. Information on FDA-approved tests for the detection of CLDN18.2 is available at https://www.fda.gov/CompanionDiagnostics.. 2.2 Prior to Administration If patient is experiencing nausea and/or vomiting prior to administration of VYLOY, the symptoms should be resolved to Grade <=1 before administering the first infusion.PremedicationPrior to each infusion of VYLOY, premedicate patients with combination of antiemetics (e.g., NK-1 receptor blockers and/or 5-HT3 receptor blockers, as well as other drugs as indicated) for the prevention of nausea and vomiting [see Warnings and Precautions (5.2)]. 2.3 Recommended Dosage Administer VYLOY in combination with fluoropyrimidine- and platinum-containing chemotherapy as follows:oFirst dose: 800 mg/m2 intravenously. oSubsequent doses: o600 mg/m2 intravenously every weeks, oro400 mg/m2 intravenously every weeks.oContinue treatment until disease progression or unacceptable toxicity.. oFirst dose: 800 mg/m2 intravenously. oSubsequent doses: o600 mg/m2 intravenously every weeks, oro400 mg/m2 intravenously every weeks.. o600 mg/m2 intravenously every weeks, or. o400 mg/m2 intravenously every weeks.. oContinue treatment until disease progression or unacceptable toxicity.. 2.4 Dosage Modifications for Adverse Reactions No dose reduction for VYLOY is recommended. Adverse reactions for VYLOY are managed by reducing the infusion rate, interruption of the infusion, withholding the dose, and/or permanently discontinuing VYLOY as described in Table 1.Table 1. Recommended Dose Modifications for VYLOY for Adverse ReactionsAdverse ReactionSeverityToxicity was graded per National Cancer Institute Common Terminology Criteria for Adverse Events Version 5.0 (NCI-CTCAE v5.0). Dose ModificationHypersensitivity or Infusion-related reactions [see Warnings and Precautions (5.1)]. Grade oInterrupt the infusion until Grade <=1, then resume at reduced infusion rate for the remaining infusion.oPremedicate and administer the next infusion per the infusion rates in Table 2.Grade 3Follow Grade management for Grade infusion-related nausea and vomiting. or or anaphylaxisoImmediately stop the infusion and permanently discontinue.. oInterrupt the infusion until Grade <=1, then resume at reduced infusion rate for the remaining infusion.. oPremedicate and administer the next infusion per the infusion rates in Table 2.. oImmediately stop the infusion and permanently discontinue.. 2.5 Preparation Reconstitution oCalculate the recommended dose based on the patients body surface area as described in Section 2.3 to determine the total volume and number of vials needed. oReconstitute each vial of VYLOY to achieve concentration of 20 mg/mL as follows: o100 mg vial add mL of Sterile Water for Injection. o300 mg vial add 15 mL of Sterile Water for Injection. oSlowly add the Sterile Water for Injection into the VYLOY vial, and direct the stream toward the inside wall of the vial. Do not inject directly onto the lyophilized powder. oSlowly swirl each vial until the contents are completely dissolved. Allow the reconstituted vial(s) to settle until the bubbles are gone. Do not shake the vial.oVisually inspect the reconstituted solution for particulate matter and discoloration. The reconstituted solution should be clear to slightly opalescent, colorless to slight yellow and free of visible particles. Discard any vial with visible particles or discoloration.oStore reconstituted vial(s) at room temperature 15C to 30C (59F to 86F) for up to hours if not used immediately. This product does not contain preservative. Dilution oWithdraw the required volume of reconstituted VYLOY vial(s) and transfer into an infusion bag containing 0.9% Sodium Chloride Injection, to final concentration of mg/mL.oThe diluted solution of VYLOY is compatible with intravenous infusion bags composed of 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.oThe diluted solution of VYLOY is compatible with infusion tubing composed of PE, PVC [with DEHP, TOTM or Di(2-ethylhexyl) terephthalate plasticizers], polybutadiene (PB), or elastomer modified polypropylene with in-line filter membranes composed of polyethersulfone (PES) or polysulfone. oMix diluted solution by gentle inversion. Do not shake the bag. oVisually inspect the infusion bag for any particulate matter prior to use. The diluted solution should be free of visible particles. Do not use the infusion bag if particulate matter is observed.oDiscard any unused portion left in the single-dose vials.Storage of diluted infusionoStore the prepared infusion bag:oAt room temperature 15C to 30C (59F to 86F) for no longer than hours from the end of the preparation of the infusion bag to the completion of the infusion.oUnder refrigeration at 2C to 8C (36F to 46F) for no longer than 16 hours from the end of the preparation of the infusion bag to the completion of the infusion. Do not freeze.. oCalculate the recommended dose based on the patients body surface area as described in Section 2.3 to determine the total volume and number of vials needed. oReconstitute each vial of VYLOY to achieve concentration of 20 mg/mL as follows: o100 mg vial add mL of Sterile Water for Injection. o300 mg vial add 15 mL of Sterile Water for Injection. o100 mg vial add mL of Sterile Water for Injection. o300 mg vial add 15 mL of Sterile Water for Injection. oSlowly add the Sterile Water for Injection into the VYLOY vial, and direct the stream toward the inside wall of the vial. Do not inject directly onto the lyophilized powder. oSlowly swirl each vial until the contents are completely dissolved. Allow the reconstituted vial(s) to settle until the bubbles are gone. Do not shake the vial.. oVisually inspect the reconstituted solution for particulate matter and discoloration. The reconstituted solution should be clear to slightly opalescent, colorless to slight yellow and free of visible particles. Discard any vial with visible particles or discoloration.. oStore reconstituted vial(s) at room temperature 15C to 30C (59F to 86F) for up to hours if not used immediately. This product does not contain preservative. oWithdraw the required volume of reconstituted VYLOY vial(s) and transfer into an infusion bag containing 0.9% Sodium Chloride Injection, to final concentration of mg/mL.oThe diluted solution of VYLOY is compatible with intravenous infusion bags composed of 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.oThe diluted solution of VYLOY is compatible with infusion tubing composed of PE, PVC [with DEHP, TOTM or Di(2-ethylhexyl) terephthalate plasticizers], polybutadiene (PB), or elastomer modified polypropylene with in-line filter membranes composed of polyethersulfone (PES) or polysulfone. oThe diluted solution of VYLOY is compatible with intravenous infusion bags composed of 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.. oThe diluted solution of VYLOY is compatible with infusion tubing composed of PE, PVC [with DEHP, TOTM or Di(2-ethylhexyl) terephthalate plasticizers], polybutadiene (PB), or elastomer modified polypropylene with in-line filter membranes composed of polyethersulfone (PES) or polysulfone.. oMix diluted solution by gentle inversion. Do not shake the bag. oVisually inspect the infusion bag for any particulate matter prior to use. The diluted solution should be free of visible particles. Do not use the infusion bag if particulate matter is observed.. oDiscard any unused portion left in the single-dose vials.. oStore the prepared infusion bag:oAt room temperature 15C to 30C (59F to 86F) for no longer than hours from the end of the preparation of the infusion bag to the completion of the infusion.oUnder refrigeration at 2C to 8C (36F to 46F) for no longer than 16 hours from the end of the preparation of the infusion bag to the completion of the infusion. Do not freeze.. oAt room temperature 15C to 30C (59F to 86F) for no longer than hours from the end of the preparation of the infusion bag to the completion of the infusion.. oUnder refrigeration at 2C to 8C (36F to 46F) for no longer than 16 hours from the end of the preparation of the infusion bag to the completion of the infusion. Do not freeze.. 2.6 Administration oAdminister VYLOY as an intravenous infusion only. Do NOT administer as an intravenous push or bolus.oIf VYLOY and fluoropyrimidine- and platinum-containing chemotherapy are administered on the same day, VYLOY must be administered first.oNo incompatibilities have been observed with oclosed system transfer devices composed of PP, PE, stainless steel, silicone (rubber/oil/resin), polyisoprene, PVC with TOTM plasticizer, acrylonitrile-butadiene-styrene (ABS) copolymer, methyl methacrylate-ABS copolymer, thermoplastic elastomer, polytetrafluoroethylene, polycarbonate, PES, acrylic copolymer, polybutylene terephthalate, PB, or EVA copolymer.ocentral ports composed of silicone rubber, titanium alloy or PVC with TOTM plasticizer.oIn-line filters (pore size of 0.2 um composed of materials listed above) are recommended to be used during administration.oDo NOT co-administer other drugs through the same infusion line.oImmediately administer the infusion as described in Table 2. To minimize the risk of adverse reactions, begin each infusion at slower rate for 30 to 60 minutes; if tolerated, gradually increase the rate as described in Table 2. oIf the infusion time exceeds the recommended storage time (6 hours from end of preparation of infusion solution at room temperature or 16 hours from end of preparation of infusion solution under refrigeration), the infusion bag must be discarded and new infusion bag prepared to continue the infusion.Infusion Rate RecommendationsTable 2. Infusion Rates Recommended for Each VYLOY InfusionVYLOY DoseInitial Infusion Rate(first 30-60 minutes)In the absence of adverse reactions after 30 to 60 minutes, the infusion rate can be increased to the subsequent infusion rate as tolerated.Subsequent Infusion RateFirst Dose800 mg/m2 100 mg/m2/hr200-265 mg/m2/hrSubsequent Doses600 mg/m2 every weeks75 mg/m2/hr150-265 mg/m2/hrororor400 mg/m2 every weeks50 mg/m2/hr100-200 mg/m2/hr. oAdminister VYLOY as an intravenous infusion only. Do NOT administer as an intravenous push or bolus.. oIf VYLOY and fluoropyrimidine- and platinum-containing chemotherapy are administered on the same day, VYLOY must be administered first.. oNo incompatibilities have been observed with oclosed system transfer devices composed of PP, PE, stainless steel, silicone (rubber/oil/resin), polyisoprene, PVC with TOTM plasticizer, acrylonitrile-butadiene-styrene (ABS) copolymer, methyl methacrylate-ABS copolymer, thermoplastic elastomer, polytetrafluoroethylene, polycarbonate, PES, acrylic copolymer, polybutylene terephthalate, PB, or EVA copolymer.ocentral ports composed of silicone rubber, titanium alloy or PVC with TOTM plasticizer.. oclosed system transfer devices composed of PP, PE, stainless steel, silicone (rubber/oil/resin), polyisoprene, PVC with TOTM plasticizer, acrylonitrile-butadiene-styrene (ABS) copolymer, methyl methacrylate-ABS copolymer, thermoplastic elastomer, polytetrafluoroethylene, polycarbonate, PES, acrylic copolymer, polybutylene terephthalate, PB, or EVA copolymer.. ocentral ports composed of silicone rubber, titanium alloy or PVC with TOTM plasticizer.. oIn-line filters (pore size of 0.2 um composed of materials listed above) are recommended to be used during administration.. oDo NOT co-administer other drugs through the same infusion line.. oImmediately administer the infusion as described in Table 2. To minimize the risk of adverse reactions, begin each infusion at slower rate for 30 to 60 minutes; if tolerated, gradually increase the rate as described in Table 2. oIf the infusion time exceeds the recommended storage time (6 hours from end of preparation of infusion solution at room temperature or 16 hours from end of preparation of infusion solution under refrigeration), the infusion bag must be discarded and new infusion bag prepared to continue the infusion.

DOSAGE FORMS & STRENGTHS SECTION.

3 DOSAGE FORMS AND STRENGTHS For injection: 100 mg and 300 mg of zolbetuximab-clzb as white to off-white lyophilized powder in single-dose vial. For injection: 100 mg and 300 mg lyophilized powder in single-dose vial. (3).

GERIATRIC USE SECTION.

8.5 Geriatric Use Of the 533 patients in clinical studies of VYLOY in combination with mFOLFOX6 or CAPOX, 34% (n=179) were over 65 years, and 5% were over 75 years (n=28) [see Clinical Studies (14)]. No overall differences in safety or effectiveness were observed between patients aged 65 years or older and younger patients.

IMMUNOGENICITY.

12.6 Immunogenicity The observed incidence of anti-drug antibody (ADA) is highly dependent on the sensitivity and specificity of the assay. Differences in assay methods preclude meaningful comparisons of the incidence of ADA in the studies described below with the incidence of ADA in other studies, including those of VYLOY or of other zolbetuximab products.During the approximately 30-month period of treatment with VYLOY 800/600 mg/m2 every weeks in combination with mFOLFOX6 or CAPOX in the clinical studies SPOTLIGHT and GLOW, the incidence of anti-zolbetuximab-clzb antibody formation was 9.5% (46 of 485 ADA-evaluable patients). Because of the low occurrence of ADAs, the effect of these antibodies on the pharmacokinetics, safety and/or effectiveness of VYLOY is unknown.

INDICATIONS & USAGE SECTION.

1 INDICATIONS AND USAGE VYLOY, in combination with fluoropyrimidine- and platinum-containing chemotherapy, is indicated for the first-line treatment of adults with locally advanced unresectable or metastatic human epidermal growth factor receptor (HER2)-negative gastric or gastroesophageal junction (GEJ) adenocarcinoma whose tumors are claudin (CLDN) 18.2 positive as determined by an FDA-approved test [see Dosage and Administration (2.1) and Clinical Studies (14)]. VYLOY is claudin 18.2-directed cytolytic antibody and is indicated in combination with fluoropyrimidine- and platinum-containing chemotherapy for the first-line treatment of adults with locally advanced unresectable or metastatic human epidermal growth factor receptor (HER2)-negative gastric or gastroesophageal junction adenocarcinoma whose tumors are claudin (CLDN) 18.2 positive as determined by an FDA-approved test (1).

ADVERSE REACTIONS SECTION.

6 ADVERSE REACTIONS The following serious adverse reactions are described elsewhere in the labeling:oHypersensitivity Reactions, including anaphylaxis, and infusion related reactions [see Warnings and Precautions (5.1)].oSevere Nausea and Vomiting [see Warnings and Precautions (5.2)].. oHypersensitivity Reactions, including anaphylaxis, and infusion related reactions [see Warnings and Precautions (5.1)].. oSevere Nausea and Vomiting [see Warnings and Precautions (5.2)].. The most common adverse reactions (>=15%) for VYLOY in combination with mFOLFOX6 or CAPOX were nausea, vomiting, fatigue, decreased appetite, diarrhea, peripheral sensory neuropathy, abdominal pain, constipation, decreased weight, hypersensitivity reactions, and pyrexia. The most common laboratory abnormalities (>=15%) for VYLOY in combination with mFOLFOX6 or CAPOX were decreased neutrophil count, decreased leucocyte count, decreased albumin, increased creatinine, decreased hemoglobin, increased glucose, decreased lymphocyte count, increased aspartate aminotransferase, decreased platelets, increased alkaline phosphatase, increased alanine aminotransferase, decreased glucose, decreased sodium, decreased phosphate, decreased potassium, and decreased magnesium (6.1). To report SUSPECTED ADVERSE REACTIONS, contact Astellas Pharma US, Inc. at 1-800-727-7003 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.The pooled safety population described in the WARNINGS AND PRECAUTIONS reflect exposure to VYLOY in 533 patients at an 800 mg/m2 initial dose followed by subsequent doses of 600 mg/m2 every weeks in combination with fluoropyrimidine- and platinum-containing chemotherapy in the SPOTLIGHT (279) and GLOW (254) studies. Among 533 patients who received VYLOY in these studies, 47% were exposed for >=6 months and 20% were exposed for >=12 months.In this pooled population, the most common (>=15%) adverse reactions, were nausea, vomiting, fatigue, decreased appetite, diarrhea, peripheral sensory neuropathy, abdominal pain, constipation, decreased weight, hypersensitivity reactions, and pyrexia. The most common (>=15%) laboratory abnormalities in the pooled population were decreased neutrophil count, decreased leucocyte count, decreased albumin, increased creatinine, decreased hemoglobin, increased glucose, decreased lymphocyte count, increased aspartate aminotransferase, decreased platelets, increased alkaline phosphatase, increased alanine aminotransferase, decreased glucose, decreased sodium, decreased phosphate, decreased potassium, and decreased magnesium.SPOTLIGHTThe safety of VYLOY was evaluated in SPOTLIGHT in patients with locally advanced unresectable or metastatic gastric or GEJ cancer who received at least one dose of VYLOY at an 800 mg/m2 initial dose followed by 600 mg/m2 subsequent doses every weeks in combination with mFOLFOX6 [see Clinical Studies (14)]. The median duration of exposure to VYLOY in combination with mFOLFOX6 was 6.2 months (range: day to 40.9 months).Serious adverse reactions occurred in 45% of patients treated with VYLOY in combination with mFOLFOX6; the most common serious adverse reactions (>=2%) were vomiting (8%), nausea (7%), neutropenia (2.9%), febrile neutropenia (2.9%), diarrhea (2.9%), intestinal obstruction (3.2%), pyrexia (2.5%), pneumonia (2.5%), respiratory failure (2.2%), pulmonary embolism (2.2%), decreased appetite (2.1%) and sepsis (2.0%). Fatal adverse reactions occurred in 5% of patients who received VYLOY in combination with mFOLFOX6 including sepsis (1.4%), pneumonia (1.1%), respiratory failure (1.1%), intestinal obstruction (0.7%), acute hepatic failure (0.4%), acute myocardial infarction (0.4%), death (0.4%), disseminated intravascular coagulation (0.4%), encephalopathy (0.4%), and upper gastrointestinal hemorrhage (0.4%). Permanent discontinuation of VYLOY due to an adverse reaction occurred in 20% of patients; the most common adverse reactions leading to discontinuation (>=2%) were nausea and vomiting.Dosage interruptions of VYLOY due to an adverse reaction occurred in 75% of patients; the most common adverse reactions leading to dose interruption (>=5%) were nausea, vomiting, neutropenia, abdominal pain, fatigue, and hypertension.Tables and summarize the most common (>=15%) adverse reactions and laboratory abnormalities with difference between arms of >=5%, respectively, compared to placebo in SPOTLIGHT.Table 3. Adverse Reactions (>=15%) in Patients Treated with VYLOY in SPOTLIGHT with Difference Between Arms of >=5% Compared to PlaceboAdverse ReactionVYLOYwith mFOLFOX6n=279Placebowith mFOLFOX6n=278All Grades %Grade or 4%All Grades%Grade or 4%Gastrointestinal disordersNausea8216617Vomiting6716366Metabolism and nutrition disordersDecreased appetite476343.2General disorders and administration site conditionsPeripheral edema180.790Table 4. Laboratory Abnormalities (>= 15%) in SPOTLIGHT with Difference Between Arms of >= 5% Compared to PlaceboLaboratory Abnormality VYLOY with mFOLFOX6The denominator used to calculate the rate varied from 271 to 272 based on the number of patients with baseline value and at least one post-treatment value.Placebo with mFOLFOX6All Grades%Grade or 4%All Grades%Grade or 4%Albumin decreased784.4471.1Potassium decreased2811216Glucose decreased450.4350.4Sodium decreased295212.9GLOWThe safety of VYLOY was evaluated in GLOW in patients with locally advanced unresectable or metastatic gastric/GEJ cancer who received at least one dose of VYLOY at an 800 mg/m2 initial dose followed by 600 mg/m2 subsequent doses every weeks in combination with CAPOX [see Clinical Studies (14)]. The median duration of exposure to VYLOY in combination with CAPOX was 4.4 months (range: 0.03 to 30.7 months).Serious adverse reactions occurred in 47% of patients treated with VYLOY in combination with CAPOX; the most common serious adverse reactions (>=2%) were vomiting (6%), nausea (4.3%), decreased appetite (3.9%), decreased platelet count (3.1%), upper gastrointestinal hemorrhage (2.8%), diarrhea (2.8%), pneumonia (2.4%), pulmonary embolism (2.3%), and pyrexia (2.0%). Fatal adverse reactions occurred in 8% of patients who received VYLOY in combination with CAPOX including sepsis (1.2%), pneumonia (0.4%), death (0.8%), upper gastrointestinal hemorrhage (0.8%), cerebral hemorrhage (0.8%), abdominal infection (0.4%), acute respiratory distress syndrome (0.4%), cardio-respiratory arrest (0.4%), decreased platelet count (0.4%), disseminated intravascular coagulation (0.4%), dyspnea (0.4%), gastric perforation (0.4%), hemorrhagic ascites (0.4%), procedural complication (0.4%), sudden death (0.4%), and syncope (0.4%). Permanent discontinuation of VYLOY due to an adverse reaction occurred in 19% of patients; the most common adverse reaction leading to discontinuation (>=2%) was vomiting.Dosage interruption of VYLOY due to an adverse reaction occurred in 55% of patients; the most common adverse reactions leading to dose interruption (>=2%) were nausea, vomiting, neutropenia, thrombocytopenia, anemia, fatigue, infusion-related reaction, and abdominal pain.Tables and summarize the most common (>=15%) adverse reactions and laboratory abnormalities with difference between arms of >=5%, respectively compared to placebo in GLOW.Table 5. Adverse Reactions (>=15%) in Patients Treated with VYLOY in GLOW with Difference Between Arms of >=5% Compared to PlaceboAdverse ReactionVYLOYwith CAPOXn=254Placebowith CAPOXn=249All Grades%Grade or 4%All Grades%Grade or 4%Gastrointestinal disordersNausea699502.4Vomiting6612313.6Metabolism and nutrition disordersDecreased appetite417341.6Blood and lymphatic system disordersNeutropenia207142.8InvestigationsWeight decreased200.4100.4Other clinically relevant adverse reactions (<15%) in GLOW with difference between arms of 5% compared to placebo included peripheral edema.Table 6. Laboratory Abnormalities (>=15%) in Patients Treated with VYLOY in GLOW with Difference Between Arms of >=5% Compared to PlaceboLaboratory Abnormality VYLOY with CAPOXThe denominator used to calculate the rate varied from 237 to 238 based on the number of patients with baseline value and at least one post-treatment value.Placebo with CAPOXAll Grades%Grade or 4%All Grades%Grade or 4%Albumin decreased663.8471.7Leukocytes decreased666608Neutrophils decreased76217014Glucose decreased240180.

CARCINOGENESIS & MUTAGENESIS & IMPAIRMENT OF FERTILITY SECTION.

13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility No studies in animals have been performed with zolbetuximab-clzb to evaluate carcinogenicity, mutagenicity, or impairment of fertility.

CLINICAL PHARMACOLOGY SECTION.

12 CLINICAL PHARMACOLOGY 12.1 Mechanism of Action Zolbetuximab-clzb is claudin 18.2 (CLDN18.2)-directed cytolytic antibody that depletes CLDN18.2-positive cells via antibody-dependent cellular cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC). Zolbetuximab-clzb in combination with chemotherapy had increased antitumor activity in CLDN18.2-expressing mouse tumor models compared to zolbetuximab-clzb or chemotherapy alone.. 12.2 Pharmacodynamics The exposure-response relationships for efficacy and safety at the recommended dosages of zolbetuximab-clzb in patients with locally advanced unresectable or metastatic HER2-negative gastric or gastroesophageal junction adenocarcinoma whose tumors are CLDN18.2 positive have not been fully characterized.. 12.3 Pharmacokinetics Following 2-hour intravenous infusion, zolbetuximab-clzb exhibited dose-proportional pharmacokinetics at doses ranging from 33 mg/m2 to 1000 mg/m2 (0.04 times to 1.25 times the recommended first dose). When administered at first dose of 800 mg/m2 followed by subsequent doses of 600 mg/m2 every weeks, steady state was achieved by 18 weeks with geometric mean (coefficient of variation [CV]%) Cmax of 415 (22%) mcg/mL and AUCtau of 3149 (37%) dayomcg/mL. Distribution The estimated geometric mean (CV%) of the steady state volume of distribution of zolbetuximab-clzb was 14.0 (59%) L.MetabolismZolbetuximab-clzb is expected to be catabolized into small peptides and amino acids.Elimination The estimated geometric mean (CV%) of the clearance (CL) and t1/2 of zolbetuximab-clzb was 0.013 (44%) L/h and 41 (62%) days, respectively. Specific PopulationsThe following factors had no clinically important effect on the clearance of zolbetuximab-clzb: age (range: 22 to 83 years), sex, race including White (50%), Asian (42%), Black (0.8%), mild to moderate (CLcr >=30 to <90 mL/min) renal impairment and mild hepatic impairment (total bilirubin (TB) <=upper limit of normal (ULN) and AST >ULN, or TB >1 to 1.5 ULN and any AST). The effect of severe renal impairment, and moderate to severe hepatic impairment is unknown.. 12.6 Immunogenicity The observed incidence of anti-drug antibody (ADA) is highly dependent on the sensitivity and specificity of the assay. Differences in assay methods preclude meaningful comparisons of the incidence of ADA in the studies described below with the incidence of ADA in other studies, including those of VYLOY or of other zolbetuximab products.During the approximately 30-month period of treatment with VYLOY 800/600 mg/m2 every weeks in combination with mFOLFOX6 or CAPOX in the clinical studies SPOTLIGHT and GLOW, the incidence of anti-zolbetuximab-clzb antibody formation was 9.5% (46 of 485 ADA-evaluable patients). Because of the low occurrence of ADAs, the effect of these antibodies on the pharmacokinetics, safety and/or effectiveness of VYLOY is unknown.

CLINICAL STUDIES SECTION.

14 CLINICAL STUDIES SPOTLIGHT The efficacy of VYLOY in combination with mFOLFOX6 was evaluated in SPOTLIGHT (NCT03504397), double-blind, randomized, multicenter study that enrolled 565 patients with locally advanced unresectable or metastatic HER2-negative gastric or GEJ adenocarcinoma whose tumors were CLDN18.2 positive. CLDN18.2 positivity (defined as >=75% of tumor cells demonstrating moderate to strong membranous CLDN18 staining) was determined by immunohistochemistry on gastric or GEJ tumor tissue specimens from all patients with the VENTANA CLDN18 (43-14A) RxDx Assay performed in central laboratory. Patients were excluded from the study if they had complete or partial gastric outlet syndrome, or history of central nervous system metastases.Patients were randomized 1:1 to receive VYLOY in combination with mFOLFOX6 (n=283) or placebo in combination with mFOLFOX6 (n=282). VYLOY was administered intravenously at an initial dose of 800 mg/m2 (Day of cycle 1) followed by subsequent doses of 600 mg/m2 every weeks in combination with up to 12 treatments (4 cycles) of mFOLFOX6 (oxaliplatin 85 mg/m2, folinic acid (leucovorin or local equivalent) 400 mg/m2, fluorouracil 400 mg/m2 given as bolus and fluorouracil 2400 mg/m2 given as continuous infusion) administered on Days 1, 15 and 29 of 42-day cycle. After 12 treatments, patients were allowed to continue treatment with VYLOY, 5-fluorouracil and folinic acid (leucovorin or local equivalent) at the discretion of the investigator, until progression of disease or unacceptable toxicity.Treatment with VYLOY continued until RECIST v1.1-defined progression of disease as determined by an independent review committee (IRC) or subsequent anticancer treatment was initiated. Tumor assessments were performed every weeks up to and including Week 54, then every 12 weeks thereafter.The major efficacy outcome measure was progression free survival (PFS) as assessed per RECIST v1.1 by IRC. Additional efficacy outcome measures were overall survival (OS), objective response rate (ORR) and duration of response (DOR) as assessed per RECIST v1.1 by IRC. The study population characteristics were median age of 61 (range: 20-86); 62% were male; 48% were White, 34% Asian, 3.0% American Indian or Alaska, 1.2% Black or African American, 4.1% other racial groups, and race in 9% was unknown or missing; 78% non-Hispanic or Latino, 13% Hispanic or Latino, and ethnicity in 10% was missing; 98% had ECOG performance status (PS) of or 1; 76% had gastric cancer, 24% had GEJ cancer; 84% were metastatic, 16% were locally advanced; and 29% had undergone prior gastrectomy. Subsequent anticancer therapy was received by 135 (48%) patients in the VYLOY in combination with mFOLFOX6 arm and 148 (53%) patients in the placebo in combination with mFOLFOX6 arm.VYLOY in combination with mFOLFOX6 demonstrated statistically significant improvement in PFS and OS compared with placebo in combination with mFOLFOX6.Table 7, Figures and summarize the efficacy results for the SPOTLIGHT study.Table 7. Efficacy Results in SPOTLIGHTEndpointVYLOYwith mFOLFOX6n=283Placebowith mFOLFOX6n=282Progression Free SurvivalNumber (%) of patients with events146 (51.6)167 (59.2)Median in months (95% CI)Based on Kaplan-Meier estimate. 10.6 (8.9, 12.5)8.7 (8.2, 10.3)Hazard ratio (95% CI)Stratification factors were region, number of metastatic sites and prior gastrectomy from IRT. Based on stratified Cox proportional hazards model. 0.751 (0.598, 0.942)1-sided p-value Based on 1-sided stratified log-rank test. 0.0066Overall survivalNumber (%) of patients with events149 (52.7)177 (62.8)Median in months (95% CI) 18.2 (16.4, 22.9)15.5 (13.5, 16.5)Hazard ratio (95% CI) 0.750 (0.601, 0.936)1-sided p-value 0.0053Objective Response Rate (CR PR)Based on confirmed response.ORR (%) (95% CI)Based on binomial distribution (Clopper-Pearson). 40.3 (34.5, 46.3)39.7 (34.0, 45.7) Complete response rate (%)14 (4.9)8 (2.8) Partial response rate (%)100 (35.3)104 (36.9)Duration of ResponseN=114N=112Median in months (95% CI)10.3 (8.3, 10.9)10.5 (7.7, 13.3)Figure 1. Kaplan Meier Plot of Progression Free Survival, SPOTLIGHT StudyFigure 2. Kaplan Meier Plot of Overall Survival, SPOTLIGHT StudyGLOW The efficacy of VYLOY in combination with CAPOX was evaluated in GLOW (NCT03653507), double-blind, randomized, multicenter study that enrolled 507 patients with locally advanced unresectable or metastatic HER2-negative gastric or GEJ adenocarcinoma whose tumors were CLDN18.2 positive. CLDN18.2 positivity (defined as >=75% of tumor cells demonstrating moderate to strong membranous CLDN18 staining) was determined by immunohistochemistry on gastric or GEJ tumor tissue specimens from all patients with the VENTANA CLDN18 (43-14A) RxDx Assay performed in central laboratory. Patients were excluded from the study if they had complete or partial gastric outlet syndrome, or history of central nervous system metastases. Patients were randomized 1:1 to receive VYLOY in combination with CAPOX (n=254) or placebo in combination with CAPOX (n=253). VYLOY was administered intravenously at an initial dose of 800 mg/m2 (Day of cycle 1) followed by subsequent dose of 600 mg/m2 every weeks in combination with up to treatments (8 cycles) of CAPOX administered on Day (oxaliplatin 130 mg/m2) and on Days to 14 (capecitabine 1000 mg/m2) of 21-day cycle. After treatments of oxaliplatin, patients were allowed to continue treatment of VYLOY and capecitabine at the discretion of the investigator, until progression of disease or unacceptable toxicity. Treatment with VYLOY continued until RECIST v1.1-defined progression of disease as determined by IRC or subsequent anticancer treatment was initiated. Tumor assessments were performed every weeks up to and including Week 54, then every 12 weeks thereafter.The major efficacy outcome measure was PFS as assessed per RECIST v1.1 by IRC. Additional efficacy outcome measures were OS, ORR, and DOR as assessed per RECIST v1.1 by IRC. The study population characteristics were median age of 60 years (range: 21-83); 62% were male; 62% were Asian, 36% were White and race in 1.4% was missing; 95% non-Hispanic or Latino, 3.4% were Hispanic or Latino and ethnicity in 1.4% was missing; 99% had ECOG performance status (PS) of or 1; 84% had primary gastric cancer, 16% had primary gastroesophageal adenocarcinoma; 88% were metastatic, 12% were locally advanced; and 27% had undergone prior gastrectomy. VYLOY in combination with CAPOX demonstrated statistically significant improvement in PFS and OS compared with placebo in combination with CAPOX. Table 8, Figures and summarize the efficacy results for the GLOW study.Table 8. Efficacy Results in GLOWEndpointVYLOYwith CAPOXn=254Placebo with CAPOXn=253Progression Free SurvivalNumber (%) of patients with events137 (53.9)172 (68.0)Median in months (95% CI)Based on Kaplan-Meier estimate. 8.2 (7.5, 8.8)6.8 (6.1, 8.1)Hazard ratio (95% CI)Stratification factors were region, number of metastatic sites and prior gastrectomy from IRT. Based on stratified Cox proportional hazards model. 0.687 (0.544, 0.866)1-sided p-value Based on 1-sided stratified log-rank test. 0.0007Overall survivalNumber (%) of patients with events144 (56.7)174 (68.8)Median in months (95% CI) 14.4 (12.3, 16.5)12.2 (10.3, 13.7)Hazard ratio (95% CI) 0.771 (0.615, 0.965)1-sided p-value 0.0118Objective Response Rate (CR PR)Based on confirmed response.ORR (%) (95% CI)Based on binomial distribution (Clopper-Pearson). 32.3 (26.6, 38.4)31.2 (25.6, 37.3) Complete response rate (%)6 (2.4)2 (0.8) Partial response rate (%)76 (29.9)77 (30.4)Duration of ResponseN=82N=79Median in months (95% CI)8.3 (6.3, 11.4)6.2 (6.0, 7.6)Figure 3. Kaplan Meier Plot of Progression Free Survival, GLOW StudyFigure 4. Kaplan Meier Plot of Overall Survival, GLOW Study. Figure 1. Figure 2. Figure 3. Figure 4.

CONTRAINDICATIONS SECTION.

4 CONTRAINDICATIONS None.. None. (4).

INFORMATION FOR PATIENTS SECTION.

17 PATIENT COUNSELING INFORMATION Advise the patient to read the FDA-approved patient labeling (Patient Information).Hypersensitivity reactions, including anaphylaxis and infusion-related reactionsAdvise patients of the risk of hypersensitivity reactions including anaphylaxis and infusion-related reactions and to contact their healthcare provider right away if they experience symptoms of hypersensitivity or infusion-related reaction during or after the administration of VYLOY. [see Warnings and Precautions (5.1)].Severe nausea and vomitingAdvise patients of the risk of severe nausea and vomiting and to immediately contact their healthcare provider if they experience persistent or worsening nausea or vomiting [see Warnings and Precautions (5.2)].LactationAdvise women not to breastfeed during treatment with VYLOY and for months after the last dose of VYLOY [see Use in Specific Populations (8.2)].Manufactured by:Astellas Pharma US, Inc. Northbrook, Illinois 60062 U.S. License 2124All trademarks are the property of their respective owners.(C)2025 Astellas Pharma US, Inc.00119-ZOL-USA.

LACTATION SECTION.

8.2 Lactation Risk SummaryThere are no data on the presence of zolbetuximab-clzb in human milk, the effects on the breastfed child, or the effects on milk production. Because antibodies may be excreted in human milk and because of the potential for adverse reactions in breastfed child, advise lactating woman not to breastfeed during treatment with VYLOY and for months after the last dose.

MECHANISM OF ACTION SECTION.

12.1 Mechanism of Action Zolbetuximab-clzb is claudin 18.2 (CLDN18.2)-directed cytolytic antibody that depletes CLDN18.2-positive cells via antibody-dependent cellular cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC). Zolbetuximab-clzb in combination with chemotherapy had increased antitumor activity in CLDN18.2-expressing mouse tumor models compared to zolbetuximab-clzb or chemotherapy alone.

NONCLINICAL TOXICOLOGY SECTION.

13 NONCLINICAL TOXICOLOGY 13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility No studies in animals have been performed with zolbetuximab-clzb to evaluate carcinogenicity, mutagenicity, or impairment of fertility.

PACKAGE LABEL.PRINCIPAL DISPLAY PANEL.

PACKAGE/LABEL PRINCIPAL DISPLAY PANEL- 100 mg/vial NDC 0469-3425-10 Rx Only VYLOY(R) zolbetuximab-clzbFOR INJECTION100 mg/vialFor intravenous infusion onlyMust reconstitute and dilute before useOne Single-dose vial. Discard unused portion. VYLOY (zolbetuximab) 100mg/vial Carton.

PEDIATRIC USE SECTION.

8.4 Pediatric Use The safety and effectiveness of VYLOY in pediatric patients have not been established.

PHARMACODYNAMICS SECTION.

12.2 Pharmacodynamics The exposure-response relationships for efficacy and safety at the recommended dosages of zolbetuximab-clzb in patients with locally advanced unresectable or metastatic HER2-negative gastric or gastroesophageal junction adenocarcinoma whose tumors are CLDN18.2 positive have not been fully characterized.

PHARMACOKINETICS SECTION.

12.3 Pharmacokinetics Following 2-hour intravenous infusion, zolbetuximab-clzb exhibited dose-proportional pharmacokinetics at doses ranging from 33 mg/m2 to 1000 mg/m2 (0.04 times to 1.25 times the recommended first dose). When administered at first dose of 800 mg/m2 followed by subsequent doses of 600 mg/m2 every weeks, steady state was achieved by 18 weeks with geometric mean (coefficient of variation [CV]%) Cmax of 415 (22%) mcg/mL and AUCtau of 3149 (37%) dayomcg/mL. Distribution The estimated geometric mean (CV%) of the steady state volume of distribution of zolbetuximab-clzb was 14.0 (59%) L.MetabolismZolbetuximab-clzb is expected to be catabolized into small peptides and amino acids.Elimination The estimated geometric mean (CV%) of the clearance (CL) and t1/2 of zolbetuximab-clzb was 0.013 (44%) L/h and 41 (62%) days, respectively. Specific PopulationsThe following factors had no clinically important effect on the clearance of zolbetuximab-clzb: age (range: 22 to 83 years), sex, race including White (50%), Asian (42%), Black (0.8%), mild to moderate (CLcr >=30 to <90 mL/min) renal impairment and mild hepatic impairment (total bilirubin (TB) <=upper limit of normal (ULN) and AST >ULN, or TB >1 to 1.5 ULN and any AST). The effect of severe renal impairment, and moderate to severe hepatic impairment is unknown.

PREGNANCY SECTION.

8.1 Pregnancy Risk SummaryThere are no data with VYLOY use in pregnant women to inform any drug-associated risks. Embryo-fetal toxicity was not observed in pregnant mice intravenously administered zolbetuximab-clzb [see Data]. VYLOY should only be given to pregnant woman if the benefit outweighs the potential risk.The background risk of major birth defects and miscarriage for the indicated population is unknown. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2%-4% and 15%-20%, respectively.DataAnimal DataIn an embryo-fetal development toxicity study, zolbetuximab-clzb was intravenously administered to pregnant mice during the period of organogenesis and did not result in embryo-fetal toxicity at doses up to 300 mg/kg (approximately 1.9 times the recommended clinical dose based on AUC). Zolbetuximab-clzb crossed the placental barrier resulting in higher fetal serum concentrations on Day 18 of gestation than maternal serum concentrations on Day 16 of gestation.

SPL PATIENT PACKAGE INSERT SECTION.

PATIENT INFORMATIONVYLOY(R) (vye-LOY)(zolbetuximab-clzb)for injectionWhat is VYLOYVYLOY is prescription medicine used to treat adults with cancer of the stomach (gastric cancer) or cancer located where the esophagus joins the stomach (gastroesophageal junction cancer). VYLOY is used in combination with chemotherapy that contains fluoropyrimidine and platinum as the first treatment when your gastric or gastroesophageal junction cancer:ocannot be removed with surgery or has spread to other parts of the body, ois HER2-negative, andoyour tumor tests positive for claudin (CLDN) 18.2.It is not known if VYLOY is safe and effective in children.Before receiving VYLOY, tell your healthcare provider about all of your medical conditions, including if you:ohave nausea or vomiting.oare pregnant or plan to become pregnant. It is not known if VYLOY will harm your unborn baby. oare breastfeeding or plan to breastfeed. It is not known if VYLOY passes into your breast milk. Do not breastfeed during treatment with VYLOY and for months after the last dose.Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements.How will receive VYLOYoVYLOY will be given to you by intravenous (IV) infusion into your vein.oYour healthcare provider will decide how much VYLOY you will receive.oYou will usually receive VYLOY every or weeks based on the chemotherapy chosen by your healthcare provider.oYour healthcare provider will decide how many treatments you need.What are the possible side effects of VYLOYVYLOY may cause serious side effects, including: oAllergic reactions, including anaphylaxis and infusion related reactions. Allergic reactions are common during treatment with VYLOY and can sometimes be serious. Serious allergic reactions can happen during or after your VYLOY infusion, including life-threatening allergic reactions and serious infusion-related reactions that may lead to death. Your healthcare provider will monitor you during your infusion and for hours after or longer if needed. Tell your healthcare provider or get emergency medical help right away if you get any of the following symptoms of serious allergic reaction during or after your infusion of VYLOY:oitchy, raised bumps on the skin (hives)ocoughing that does not go awayonausea or vomitingostomach (abdominal) painoincreased salivaobreathing problems such as wheezingothroat tightness or change in voiceofeverochest discomfortochills or shakingoback painoSevere nausea and vomiting. Nausea and vomiting are common during treatment with VYLOY and can sometimes be severe. Nausea and vomiting happened more often during the first treatment cycle. Before you receive each VYLOY infusion, your healthcare provider will give you medicines to help prevent nausea and vomiting. Tell your healthcare provider right away if nausea or vomiting does not go away or gets worse.The most common side effects of VYLOY include:otirednessodecreased appetiteodiarrheaotingling or numbness of the arms or legsostomach (abdominal) painoconstipationodecreased weightofeverodecreased white blood cells, red blood cells and plateletsodecreased protein (albumin) in the bloodochanges in kidney function testsochanges in blood sugar (glucose) ochanges in liver function testsochanges in body salts (electrolytes) in your bloodYour healthcare provider may slow the rate of your infusion, temporarily stop, or completely stop treatment with VYLOY if you have certain side effects.These are not all of the possible side effects of VYLOY.Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.General information about the safe and effective use of VYLOY.Medicines are sometimes prescribed for purposes other than those listed in Patient Information leaflet. You can ask your pharmacist or healthcare provider for information about VYLOY that is written for health professionals.What are the ingredients in VYLOYActive ingredient: zolbetuximab-clzbInactive ingredients: arginine, polysorbate 80, sucrose, and phosphoric acid to adjust pH.Manufactured by:Astellas Pharma US, Inc. Northbrook, Illinois 60062 U.S. License 2124(C)2025 Astellas Pharma US, Inc.00119-ZOL-USAFor more information, go to www.VYLOY.com or call 1-888-727-7003.This Patient Information has been approved by the U.S. Food and Drug Administration. Revised: 6/2025. ocannot be removed with surgery or has spread to other parts of the body, ois HER2-negative, and. oyour tumor tests positive for claudin (CLDN) 18.2.. ohave nausea or vomiting.. oare pregnant or plan to become pregnant. It is not known if VYLOY will harm your unborn baby. oare breastfeeding or plan to breastfeed. It is not known if VYLOY passes into your breast milk. Do not breastfeed during treatment with VYLOY and for months after the last dose.. oVYLOY will be given to you by intravenous (IV) infusion into your vein.. oYour healthcare provider will decide how much VYLOY you will receive.. oYou will usually receive VYLOY every or weeks based on the chemotherapy chosen by your healthcare provider.. oYour healthcare provider will decide how many treatments you need.. oAllergic reactions, including anaphylaxis and infusion related reactions. Allergic reactions are common during treatment with VYLOY and can sometimes be serious. Serious allergic reactions can happen during or after your VYLOY infusion, including life-threatening allergic reactions and serious infusion-related reactions that may lead to death. Your healthcare provider will monitor you during your infusion and for hours after or longer if needed. Tell your healthcare provider or get emergency medical help right away if you get any of the following symptoms of serious allergic reaction during or after your infusion of VYLOY:. oitchy, raised bumps on the skin (hives). ocoughing that does not go away. onausea or vomiting. ostomach (abdominal) pain. oincreased saliva. obreathing problems such as wheezing. othroat tightness or change in voice. ofever. ochest discomfort. ochills or shaking. oback pain. oSevere nausea and vomiting. Nausea and vomiting are common during treatment with VYLOY and can sometimes be severe. Nausea and vomiting happened more often during the first treatment cycle. Before you receive each VYLOY infusion, your healthcare provider will give you medicines to help prevent nausea and vomiting. Tell your healthcare provider right away if nausea or vomiting does not go away or gets worse.. otiredness. odecreased appetite. odiarrhea. otingling or numbness of the arms or legs. ostomach (abdominal) pain. oconstipation. odecreased weight. ofever. odecreased white blood cells, red blood cells and platelets. odecreased protein (albumin) in the blood. ochanges in kidney function tests. ochanges in blood sugar (glucose) ochanges in liver function tests. ochanges in body salts (electrolytes) in your blood.