Access and resources focused on supporting patients treated with VYLOY

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: As long as I’ve been an oncology nurse, it still gets to me every time I see a patient for their first cancer treatment infusion. The worry on their face breaks my heart.

NURSE 2: I feel the same. They don’t know what to expect, or how they’ll feel. It’s a lot of unknowns.

NURSE 1: But you know what? When I’ve done my homework, I can help my patients be better prepared for infusion day.

NURSE 2: I know, there are several VYLOY resources that have helped me learn what to expect and how to support my patients.

NURSE 1: You know what works for me? I took those resources and came up with an infusion-day check list to help keep me organized.

NURSE 2: How’s that work?

NURSE 1: First I start with the technical things I need to do as far as the infusion goes—like checking the IV line.

NURSE 1: I always make sure I’m using the recommended in-line filter and that I do not co-administer other drugs through the same infusion line as VYLOY.

NURSE 2: But what about patients who have central ports?

NURSE 1: From what I’ve read, no incompatibilities have been observed with closed system transfer devices or central ports with certain materials. The Prescribing Information has the full details.

NURSE 2: That’s really helpful to know.

NURSE 2: So what’s next on your checklist?

NURSE 1: I double check the prepared infusion bag and note the time. The prepared infusion bag can be kept at room temperature, 15 to 30 degrees Celsius or 59 to 86 degrees Fahrenheit, for no longer than 6 hours, from the end of the preparation of the infusion bag to the completion of the infusion. Once I’m done, I start with my patient checklist.

NURSE 2: I bet I know where that starts...

BOTH: Premedication

NURSE 1: Absolutely. These patients can be pretty sick, so I always ask how they’re feeling, especially if it’s their first infusion.

NURSE 1: If they tell me they’re nauseated or they’ve been vomiting, I make sure their symptoms are reduced to Grade 1 or less before we start the first infusion.

VYLOY is emetogenic. In clinical trials, the median time to onset of nausea and/or vomiting was within the first hour after starting the VYLOY infusion. It’s important that patients are premedicated with a combination of antiemetics like NK-1 and/or 5-HT3 receptor blockers, as well as other drugs as indicated, for the prevention of nausea and vomiting. Keep in mind that there are no contraindications for VYLOY. I always let my patients know in advance that they can expect premedication with every VYLOY infusion.

NURSE 2: I think that’s a big reassurance for the patient...to know that we’re doing everything we can to help them.

NURSE 1: Exactly...and if they do experience Grade 2 or 3 nausea or vomiting, I’ll stop the infusion until the symptoms are resolved to Grade 1 or less. Then I resume the infusion at a reduced infusion rate for the remaining infusion. If the patient experiences Grade 4 vomiting, I need to immediately stop the infusion and permanently discontinue VYLOY.

NURSE 1: The prescribing information shows the infusion rates for first and subsequent infusions. I like to use this information to help patients understand how long their infusions might take.

I explain that their first VYLOY dose may take longer than their next infusions—and that all VYLOY infusions start at a slower rate for the first 30 to 60 minutes to help minimize the risk of adverse reactions. For example, for their first VYLOY infusion, the initial infusion rate will be 100 milligrams per meter squared per hour the first 30 to 60 minutes. If there are no adverse reactions after 30 to 60 minutes, the infusion can be increased to the subsequent infusion rate shown in the Prescribing Information as tolerated.

NURSE 1: How long each infusion lasts depends on different things, including potential infusion interruptions or rate modifications. The first infusion is estimated to take a minimum of 3 and a half hours. Subsequent infusions are estimated to take a minimum of 2 and a half hours. 

NURSE 2: That’s good to know because infusion days can be pretty long, so it helps to be able to give patients and caregivers an idea of what to expect.

NURSE 1: Oh! That reminds me... I always check to see if my patient is getting VYLOY and chemo on the same day. If so, VYLOY must be administered first.

NURSE 2: Thanks for all the great advice. I have a patient starting on VYLOY tomorrow. Mind if I use some of your ideas?

NURSE 1: Sure. I’ll bill you later.

(BOTH LAUGH)

NURSE 1: Just to recap, here are a few important things to remember.

Make sure the prepared VYLOY infusion bag is stored no longer than 6 hours at room temperature from the end of the preparation of the infusion bag to the completion of the infusion.

VYLOY is emetogenic. The most common adverse reactions were nausea and vomiting. Patients have to be premedicated with a combination of antiemetics like NK-1 and/or 5-HT3 receptor blockers as well as other drugs as clinically indicated. We can refer to the Prescribing Information for details. 

The infusion should start at a slower rate for the first 30 to 60 minutes. If tolerated, we can gradually increase the rate as recommended. 

If nausea and vomiting become Grade 2 or 3, stop the infusion. Once the symptoms are Grade 1 or less, restart it at a reduced infusion rate for the remaining infusion.

NURSE 1: You can find all of this in the VYLOY Prescribing Information.

NURSE 2: I’m so glad we talked. I know when I feel good about things, I can make a difference for my patient, too. Thanks!

NURSE 1: You’ve got this.

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.

Please see Important Safety Information and full Prescribing Information at VYLOYhcp.com.

Find more videos, information on VYLOY, and other resources at VYLOYhcp-dot-com.

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: When I first started learning about VYLOY, I was glad that there was a CLDN18.2-targeted treatment for our patients with advanced gastric or GEJ cancer.

NURSE 2: Those cancers are pretty rare, and there aren’t a lot of options for most patients. So I’m happy they have another first-line treatment choice available.

NURSE 1: I mean, we’ve never had a treatment to target this biomarker before VYLOY. And then I thought about giving my first infusion with VYLOY and chemo, and I realized…I really should study up!

(BOTH LAUGH)

NURSE 2: I know what you mean. I have a new patient starting on VYLOY soon so I’m trying to learn all I can. The first thing I wanted to know was how the treatment schedules with VYLOY and chemo would affect my patients.

NURSE 1: Me, too. I read in the Infusion and Treatment Management Guide that VYLOY can be given every two or every three weeks, so it’s great to know our patients’ VYLOY treatment aligns with their prescribed chemo schedule.

NURSE 1: In fact, we can give VYLOY and chemo on the same day, but VYLOY must be administered first.

NURSE 2: The first dose is higher at 800 milligrams per meter squared, subsequent doses are either 600 milligrams per meter squared every 3 weeks or 400 milligrams per meter squared every 2 weeks.

NURSE 2: If a patient has preexisting nausea or vomiting, the symptoms should be resolved to Grade 1 or less before we start their first VYLOY infusion. Prior to each infusion, patients should be premedicated with a combination of antiemetics to help prevent nausea and vomiting.

NURSE 1: VYLOY can only be given as an infusion, right?

NURSE 2: One hundred percent. VYLOY cannot be administered as an IV push or bolus. There’s also a matter of storage timing.

NURSE 1: What do you mean?

NURSE 2: Once the VYLOY infusion bag preparation is complete, the diluted infusion should be stored for no longer than 16 hours under refrigeration or no longer than 6 hours at room temperature.

NURSE 1: So that means we have 6 hours from the end of bag preparation to the completion of the infusion.

NURSE 2: Right. And if the infusion time exceeds the recommended storage time, we have to discard the infusion bag and prepare a new one to continue the infusion.

NURSE 1: So with that kind of timeframe, and because my patients always ask, how do you explain how long VYLOY infusions will take?

NURSE 2: I start by letting them know that to minimize risk of adverse reactions, each infusion starts at a slower rate for 30 to 60 minutes, and if tolerated, the rate is gradually increased as recommended in the Prescribing Information.

NURSE 2: The first infusion of VYLOY is estimated to take a minimum of 3 and a half hours. Each following dose may take less time. The timing really depends on potential infusion interruptions or if we have to modify the infusion rate. After the patient’s VYLOY infusion is complete, their chemo infusion could take another 2 to 3 hours based on their prescribed chemotherapy.

NURSE 1: Subsequent doses may be a little shorter but in general it can be a long day for patients. I always tell patients up front so they and their caregivers can arrange transportation, plan for snacks, and pack whatever they’ll need for the day. It’s just something I keep in mind when scheduling patients.

NURSE 2: Good plan. Everyone’s different in what they need and how they feel. Being able to set expectations for our patients and caregivers will help them have a better grasp of what their infusion day will look like.

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.

Please see Important Safety Information and full Prescribing Information at VYLOYhcp.com.

Find more videos, information on VYLOY, and other resources at VYLOYhcp-dot-com.

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.

VYLOY^® (zolbetuximab-clzb): A Novel Treatment That Targets Claudin 18.2-positive (CLDN18.2+), HER2-negative Locally Advanced Unresectable, or Metastatic Gastric or Gastroesophageal Junction Adenocarcinoma

Descriptions of the VYLOY mechanism of action are based on preclinical data.

VYLOY is a first-in-class monoclonal antibody indicated in combination with fluoropyrimidine- and platinum-containing chemotherapy for the first-line treatment of adult patients with locally advanced unresectable or metastatic human epidermal growth factor receptor 2 (HER2)-negative gastric or gastroesophageal junction adenocarcinoma whose tumors are claudin 18.2 positive as determined by an FDA-approved test.

Preclinical studies have shown that VYLOY is a claudin 18.2 directed cytolytic antibody that selectively binds to cells that express claudin 18.2, where cytotoxic immune responses are activated.

Claudin 18.2 Overview

Claudin 18.2 is present in gastric and gastroesophageal junction adenocarcinoma.

According to estimates from two global Phase 3 studies, 38% of patients with locally advanced unresectable or metastatic gastric or gastroesophageal junction adenocarcinoma are claudin 18.2-positive, which was defined as 75% or more of tumor cells demonstrating moderate to strong membranous claudin 18.2 staining by immunohistochemistry.

Claudin 18.2 may become more exposed and accessible to antibodies as gastric tumors develop.

To understand the relevance of this protein to these types of cancers, let’s take a closer look at the role of claudin 18.2 within healthy gastric mucosal tissue.

Claudin 18 in Healthy Gastric Tissue

Claudin 18 is a member of the Claudin family of transmembrane tight junction proteins.

Claudin 18.2 is the dominant claudin 18 isoform found in normal healthy gastric tissue and is typically buried within tight junctions.

As a component of tight junctions, claudins are involved in the regulation of permeability, barrier function, and polarity of epithelial layers.

Claudin 18.2 Overview

Now that we’ve explored the role of claudin 18.2 in normal tissue, let’s examine what happens in gastric adenocarcinomas.

Claudin 18.2 is often retained during malignant transformation, when cell polarity disruptions and structure loss occur.

As a result, claudin 18.2 may become more exposed and accessible to antibodies as gastric tumors develop.

Claudin 18.2 may also be expressed in lymph node metastases of gastric adenocarcinoma as well as other distant metastatic sites.

The Mechanism of Action for VYLOY

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. 

VYLOY is a claudin 18.2-directed cytolytic antibody that selectively binds to cells that express claudin 18.2.

When this binding occurs, cytotoxic immune responses are activated.

This is achieved through the induction of antibody-dependent cell-mediated cytotoxicity, or ADCC, and complement-dependent cytotoxicity, or CDC, leading to the destruction of cancer cells.

Let’s take a look at how VYLOY-mediated activation of ADCC and CDC may result in cancer cell depletion.

During ADCC, effector cells, such as natural killer cells, recognize antibody-targeted tumor cells and release cytotoxic molecules that cause tumor cell lysis. 

At the same time, the induction of CDC gathers complement proteins at the tumor site or sites where they converge and assemble a membrane attack complex which forms pores on the tumor cell surface causing lysis of the tumor cell.

Through VYLOY-induced ADCC and CDC, claudin 18.2-positive gastric tumor cells are depleted.

Combining VYLOY and Chemotherapy

In addition to the action of VYLOY binding to claudin 18.2-positive gastric adenocarcinoma cells, it’s important to consider what happens when this cytolytic antibody is combined with chemotherapy.

In the presence of the combination of chemotherapy and VYLOY, the antitumor effect has been shown to be increased compared to chemotherapy or VYLOY alone (in claudin 18.2-expressing mouse models).

VYLOY represents a novel approach to treating cancer, and is the first-in-class monoclonal antibody to target the novel claudin 18.2 biomarker, mediating the immune system mechanisms, ADCC and CDC, in locally advanced unresectable or metastatic HER2-negative gastric or gastroesophageal junction adenocarcinoma.

IMPORTANT SAFETY INFORMATION

WARNINGS AND PRECAUTIONS

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.