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*PFS was assessed per RECIST v1.1 by independent review committee (IRC).1
†Based on Kaplan-Meier estimate.1
CI=confidence interval; HR=hazard ratio; RECIST=Response Evaluation Criteria in Solid Tumors.
*Based on Kaplan-Meier estimate.1
LIMITATIONS: The results below are from exploratory analyses that were not prespecified within the SPOTLIGHT protocol and were not statistically powered to detect differences between treatment arms; therefore, no conclusions can be drawn. These results are provided only as descriptive clinical information.
Study population: Median age was 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, 9% race unknown or missing; 78% non-Hispanic or Latino, 13% Hispanic or Latino, and 10% ethnicity missing. 98% had ECOG performance status (PS) of 0 or 1. 76% had gastric cancer, 24% had GEJ cancer, 84% were metastatic, 16% were locally advanced, and 29% had prior gastrectomy. Subsequent anticancer therapy: 135 (48%) patients in the VYLOY + mFOLFOX6 arm and 148 (53%) patients in the placebo + mFOLFOX6 arm.1 Lauren classification: 35% diffuse, 24% intestinal, 8% mixed, 16% unknown, 16% other, and 1% missing.2
*Claudin 18.2+ (CLDN18.2 positive) is defined as ≥75% of tumor cells demonstrating moderate to strong membranous CLDN18 staining by IHC.2
†HER2- tumor as determined by local or central testing.2
‡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 1 of Cycle 1) followed by subsequent doses of 600 mg/m2 every 3 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 a bolus and fluorouracil 2400 mg/m2 given as a continuous infusion) administered on Days 1, 15, and 29 of a 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.1
§Treatment continued until RECIST v1.1-defined progression of disease as determined by an independent review committee (IRC).1
||Assessed per RECIST v1.1 by IRC.1
¶Does not include all patient inclusion and exclusion criteria for the SPOTLIGHT trial.2
CLDN18.2=claudin 18.2; CNS=central nervous system; ECOG=Eastern Cooperative Oncology Group; G/GEJ=gastric/gastroesophageal junction; HER2=human epidermal growth factor receptor 2.
Nausea and vomiting have been confirmed as important identified risks. Adverse events, graded according to National Cancer Institute Common Terminology Criteria for Adverse Events version 4.03, were monitored throughout the trial and for 90 days after treatment discontinuation. Adverse event preferred terms were defined according to the Medical Dictionary for Regulatory Activities terminology version 25.0. Grade 4 nausea is not defined in Common Terminology Criteria For Adverse Events v4.03 and was determined and managed at investigator discretion. These data are not generalizable and cannot be used to predict adverse event outcomes. These data are from the safety analysis set (SAS) in a Phase 3, global, randomized, multicenter trial (VYLOY + mFOLFOX6: n=279; Placebo + mFOLFOX6: n=278). The results presented are provided only as descriptive clinical information.
*PFS was assessed per RECIST v1.1 by independent review committee (IRC).1
†Based on Kaplan-Meier estimate.1
CI=confidence interval; HR=hazard ratio; RECIST=Response Evaluation Criteria in Solid Tumors.
*Based on Kaplan-Meier estimate.1
LIMITATIONS: The results below are from exploratory analyses that were not prespecified within the GLOW protocol and were not statistically powered to detect differences between treatment arms; therefore, no conclusions can be drawn. These results are provided only as descriptive clinical information.
*Estimate based on Kaplan-Meier method.4
Study population: Median age was 60 (range: 21-83). 62% were male. 62% were Asian, 36% White, 1.4% race missing; 95% non-Hispanic or Latino, 3.4% Hispanic or Latino, and 1.4% ethnicity missing. 99% had ECOG performance status (PS) of 0 or 1. 84% had primary gastric cancer, 16% had primary GEJ cancer, 88% were metastatic, 12% were locally advanced, and 27% had prior gastrectomy.1 Lauren classification: 37% diffuse, 15% intestinal, 8% mixed, 28% unknown, 12% other, and 1% missing.4
*Claudin 18.2+ (CLDN18.2 positive) is defined as ≥75% of tumor cells demonstrating moderate to strong membranous CLDN18 staining by IHC.4
†HER2- tumor as determined by local or central testing.4
‡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 1 of Cycle 1) followed by subsequent doses of 600 mg/m2 every 3 weeks in combination with up to 8 treatments (8 cycles) of CAPOX administered on Day 1 (oxaliplatin 130 mg/m2) and on Days 1 to 14 (capecitabine 1000 mg/m2) of a 21-day cycle. After 8 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.1
§Treatment continued until RECIST v1.1-defined progression of disease as determined by an independent review committee (IRC).1
||Assessed per RECIST v1.1 by IRC.1
¶Does not include all patient inclusion and exclusion criteria for the GLOW trial.4
CLDN18.2=claudin 18.2; CNS=central nervous system; ECOG=Eastern Cooperative Oncology Group; G/GEJ=gastric/gastroesophageal junction; HER2=human epidermal growth factor receptor 2.
Nausea and vomiting have been confirmed as important identified risks. Adverse events, graded according to National Cancer Institute Common Terminology Criteria for Adverse Events version 4.03, were monitored throughout the trial and for 90 days after treatment discontinuation. Adverse event preferred terms were defined according to the Medical Dictionary for Regulatory Activities terminology version 25.0. Grade 4 nausea is not defined in Common Terminology Criteria For Adverse Events v4.03 and was determined and managed at investigator discretion. These data are not generalizable and cannot be used to predict adverse event outcomes. These data are from the safety analysis set (SAS) in a Phase 3, global, randomized, multicenter trial (VYLOY + CAPOX: n=254; Placebo + CAPOX: n=249). The results presented are provided only as descriptive clinical information.
*The onset day in the onset interval was defined as the date of onset minus the date of first dose plus 1.
Watch a conversation that provides helpful insights and guidance for nurses on managing and monitoring hypersensitivity and infusion-related reactions.
INDICATION
VYLOY® (zolbetuximab-clzb), 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 2 (HER2)-negative gastric or gastroesophageal junction (GEJ) adenocarcinoma whose tumors are claudin (CLDN) 18.2 positive as determined by an FDA-approved test.
IMPORTANT SAFETY INFORMATION
WARNINGS AND PRECAUTIONS
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 3 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 2 (0.4%) patients who received VYLOY. An IRR led to permanent discontinuation of VYLOY in 2 (0.4%) patients and dose interruption in 7 (1.3%) patients. The infusion rate was reduced for VYLOY for 2 (0.4%) patients due to an IRR. Monitor patients during infusion with VYLOY and for 2 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 a 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 2 hypersensitivity or IRR, interrupt the VYLOY infusion until Grade ≤1, then resume at a reduced infusion rate for the remaining infusion. Follow Grade 2 management for Grade 3 infusion-related nausea and vomiting. Premedicate the patient with antihistamines for the subsequent infusions, and closely monitor the patient for symptoms and signs of a hypersensitivity reaction. The infusion rate may be gradually increased as tolerated.
Please see Important Safety Information continued in this video and full Prescribing Information at VYLOYhcp.com.
NURSE 1: One of the common questions I get when patients find out they’ll be receiving VYLOY plus chemo is, “What kind of side effects might I have?”
NURSE 2: I know. They worry about things like nausea and vomiting with treatment. Thankfully there are things we can do before and during treatment to help manage these side effects.
NURSE 1: Did you know in the SPOTLIGHT trial, nausea and vomiting were the most common adverse reactions in patients who received VYLOY and mFOLFOX6?
NURSE 2: That would make sense because the USPI shows that VYLOY is emetogenic. We have to be prepared because in clinical trials, the median time to onset of nausea and/or vomiting was within the first hour after starting the VYLOY infusion. Some patients may experience vomiting before they have any nausea.
I mean, some of these patients may have preexisting nausea and vomiting, and if they do, we have to make sure their symptoms are resolved to Grade 1 or less before we start their first infusion.
NURSE 1: Exactly. And before each VYLOY infusion, the Prescribing Information says to premedicate patients with a combination of antiemetics, like NK-1 receptor blockers and/or 5-HT3 receptor blockers, as well as other drugs as indicated for the prevention of nausea and vomiting. Something also to note is that there are no contraindications for VYLOY.
NURSE 2: You know, one thing that struck me as I was learning about VYLOY is that no dose reduction is recommended for adverse reactions.
NURSE 1: Adverse reactions for VYLOY are managed by reducing the infusion rate, interrupting the infusion, withholding the dose, or permanently discontinuing treatment.
NURSE 2: For hypersensitivity and infusion-related reactions, including nausea and vomiting, the VYLOY Prescribing Information provides guidance for us to follow.
For example, if a patient experiences Grade 2 or 3 infusion-related nausea and vomiting, it’s recommended to interrupt the infusion until the symptoms are resolved to Grade 1 or less. Then we can resume the infusion at a reduced infusion rate for the remaining infusion.
We’ll premedicate and administer the patient’s next infusion at the recommended infusion rates.
NURSE 1: At what point would VYLOY be discontinued because of infusion-related nausea and vomiting?
NURSE 2: If vomiting is Grade 4, it’s recommended to immediately stop the infusion, and treatment would be permanently discontinued.
NURSE 1: What about hypersensitivity and other infusion-related reactions?
NURSE 2: Good question. Besides monitoring patients for infusion-related reactions, including nausea and vomiting, we also need to monitor them for hypersensitivity reactions during the infusion and for at least 2 hours after if clinically indicated.*
*Patients should be monitored during the infusion with VYLOY for hypersensitivity reactions. If clinically indicated, patients should be monitored for 2 hours after the completion of the infusion or longer. This observation period after the infusion is a recommendation (not a requirement) based upon clinician’s judgement and can occur while other chemotherapy agents are being administered.
NURSE 1: You’re talking about anaphylaxis, right? So we should look for things like urticaria, repetitive cough, wheezing, tightness in the throat, or change in voice.
NURSE 2: You got it. The USPI gives us more details on what to watch out for with hypersensitivity and infusion-related reactions like nausea and vomiting.
NURSE 1: When I talk to my patients about nausea and vomiting, I like to share some of the insights I learned from the Prescribing Information and the SPOTLIGHT study.
NURSE 2: I agree. When I reviewed the package insert, I saw that nausea and vomiting should be managed during and after the infusion with antiemetics or fluid replacement. Based on severity, it is recommended to interrupt the infusion or permanently discontinue VYLOY.
NURSE 1: Keep in mind nausea and vomiting were the most common adverse reactions with VYLOY and mFOLFOX6 in the SPOTLIGHT trial, and the majority were Grades 1 and 2.
NURSE 2: Yeah, that’s pretty important for patients to know, but there’s something else I share with my patients…
NURSE 2: … and that’s the fact that nausea occurred more often during the first treatment cycle with VYLOY plus chemotherapy and decreased in incidence with subsequent cycles.
NURSE 2: The same was true for vomiting. It also occurred more frequently in the first cycle.
NURSE 1: I should point out that the Prescribing Information shows that with VYLOY plus mFOLFOX6, 16% of patients experienced Grade 3 or 4 nausea and/or vomiting in the SPOTLIGHT trial.
That being said, nausea or vomiting led to the permanent discontinuation of VYLOY in combination with mFOLFOX6 or CAPOX in less than 4% of patients.
NURSE 2: It’s really helpful to know there are ways we can help manage adverse reactions like nausea and vomiting for our patients receiving VYLOY with chemo.
NURSE 1: And it’s important to let them know it, too.
IMPORTANT SAFETY INFORMATION (continued)
WARNINGS AND PRECAUTIONS (continued)
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. Manage patients during and after infusion with antiemetics or fluid replacement. Interrupt the infusion, or permanently discontinue VYLOY based on severity.
ADVERSE REACTIONS
Most common adverse reactions (≥15%): Nausea, vomiting, fatigue, decreased appetite, diarrhea, peripheral sensory neuropathy, abdominal pain, constipation, decreased weight, hypersensitivity reactions, and pyrexia.
Most common laboratory abnormalities (≥15%): 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, increased phosphate, decreased potassium, and decreased magnesium.
SPOTLIGHT Study: 279 patients with locally advanced unresectable or metastatic HER2-negative gastric or GEJ adenocarcinoma whose tumors were CLDN18.2 positive who received at least one dose of VYLOY in combination with mFOLFOX6
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.
GLOW Study: 254 patients with locally advanced unresectable or metastatic HER2-negative gastric or GEJ adenocarcinoma whose tumors were CLDN18.2 positive who received at least one dose of VYLOY in combination with CAPOX
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.
SPECIFIC POPULATIONS
Lactation Advise lactating women not to breastfeed during treatment with VYLOY and for 8 months after the last dose.
Find more videos, information on VYLOY, and other resources at VYLOYhcp.com.
To see more educational videos on VYLOY, click here.
*Fluoropyrimidine- and platinum-containing chemotherapy.1
IHC=immunohistochemistry.
INDICATION
IMPORTANT SAFETY INFORMATION
INDICATION
VYLOY® (zolbetuximab-clzb), 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 2 (HER2)-negative gastric or gastroesophageal junction (GEJ) adenocarcinoma whose tumors are claudin (CLDN) 18.2 positive as determined by an FDA-approved test.
WARNINGS AND PRECAUTIONS
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 3 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 2 (0.4%) patients who received VYLOY. An IRR led to permanent discontinuation of VYLOY in 2 (0.4%) patients and dose interruption in 7 (1.3%) patients. The infusion rate was reduced for VYLOY for 2 (0.4%) patients due to an IRR. Monitor patients during infusion with VYLOY and for 2 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 a 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 2 hypersensitivity or IRR, interrupt the VYLOY infusion until Grade ≤1, then resume at a reduced infusion rate for the remaining infusion. Follow Grade 2 management for Grade 3 infusion-related nausea and vomiting. Premedicate the patient with antihistamines for the subsequent infusions, and closely monitor the patient for symptoms and signs of a hypersensitivity reaction. The infusion rate may be gradually increased as tolerated.
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. Manage patients during and after infusion with antiemetics or fluid replacement. Interrupt the infusion, or permanently discontinue VYLOY based on severity.
ADVERSE REACTIONS
Most common adverse reactions (≥15%): Nausea, vomiting, fatigue, decreased appetite, diarrhea, peripheral sensory neuropathy, abdominal pain, constipation, decreased weight, hypersensitivity reactions, and pyrexia.
Most common laboratory abnormalities (≥15%): 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, increased phosphate, decreased potassium, and decreased magnesium.
SPOTLIGHT Study: 279 patients with locally advanced unresectable or metastatic HER2-negative gastric or GEJ adenocarcinoma whose tumors were CLDN18.2 positive who received at least one dose of VYLOY in combination with mFOLFOX6
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.
GLOW Study: 254 patients with locally advanced unresectable or metastatic HER2-negative gastric or GEJ adenocarcinoma whose tumors were CLDN18.2 positive who received at least one dose of VYLOY in combination with CAPOX
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.
SPECIFIC POPULATIONS
Lactation Advise lactating women not to breastfeed during treatment with VYLOY and for 8 months after the last dose.
Please see full Prescribing Information.
References:
INDICATION
IMPORTANT SAFETY INFORMATION
INDICATION
VYLOY® (zolbetuximab-clzb), 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 2 (HER2)-negative gastric or gastroesophageal junction (GEJ) adenocarcinoma whose tumors are claudin (CLDN) 18.2 positive as determined by an FDA-approved test.
WARNINGS AND PRECAUTIONS
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 3 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 2 (0.4%) patients who received VYLOY. An IRR led to permanent discontinuation of VYLOY in 2 (0.4%) patients and dose interruption in 7 (1.3%) patients. The infusion rate was reduced for VYLOY for 2 (0.4%) patients due to an IRR. Monitor patients during infusion with VYLOY and for 2 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 a 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 2 hypersensitivity or IRR, interrupt the VYLOY infusion until Grade ≤1, then resume at a reduced infusion rate for the remaining infusion. Follow Grade 2 management for Grade 3 infusion-related nausea and vomiting. Premedicate the patient with antihistamines for the subsequent infusions, and closely monitor the patient for symptoms and signs of a hypersensitivity reaction. The infusion rate may be gradually increased as tolerated.
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. Manage patients during and after infusion with antiemetics or fluid replacement. Interrupt the infusion, or permanently discontinue VYLOY based on severity.
ADVERSE REACTIONS
Most common adverse reactions (≥15%): Nausea, vomiting, fatigue, decreased appetite, diarrhea, peripheral sensory neuropathy, abdominal pain, constipation, decreased weight, hypersensitivity reactions, and pyrexia.
Most common laboratory abnormalities (≥15%): 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, increased phosphate, decreased potassium, and decreased magnesium.
SPOTLIGHT Study: 279 patients with locally advanced unresectable or metastatic HER2-negative gastric or GEJ adenocarcinoma whose tumors were CLDN18.2 positive who received at least one dose of VYLOY in combination with mFOLFOX6
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.
GLOW Study: 254 patients with locally advanced unresectable or metastatic HER2-negative gastric or GEJ adenocarcinoma whose tumors were CLDN18.2 positive who received at least one dose of VYLOY in combination with CAPOX
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.
SPECIFIC POPULATIONS
Lactation Advise lactating women not to breastfeed during treatment with VYLOY and for 8 months after the last dose.
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