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- SPOTLIGHT Trial (mFOLFOX6)
- GLOW Trial (CAPOX)
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Progression-free Survival -
Overall Survival -
Response Data -
Exploratory Data -
Study Design -
Safety Profile
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Median PFS was 10.6 months with VYLOY + mFOLFOX6 vs 8.7 months with mFOLFOX6 alone (HR=0.75 [95% CI: 0.60-0.94]; P=0.0066).1
*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.
Overall survival (OS) was significantly improved with VYLOY + mFOLFOX6 vs mFOLFOX6 alone1
Median OS was 18.2 months with VYLOY + mFOLFOX6 vs 15.5 months with mFOLFOX6 alone (HR=0.75 [95% CI: 0.60-0.94]; P=0.0053).1
*Based on Kaplan-Meier estimate.1
Response rates from the SPOTLIGHT Phase 3 trial
*ORR based on binomial distribution (Clopper-Pearson).1
†ORR and DOR were assessed by IRC per RECIST v1.1.1
DOR=duration of response; ORR=objective response rate.
Progression-free survival and overall survival at 12 and 24 months2
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.
PFS at 12 and 24 months2*
| DURATION | VYLOY + mFOLFOX6 | PLACEBO + mFOLFOX6 |
|---|---|---|
| At 12 months | 49% | 35% |
| At 24 months | 24% | 15% |
OS at 12 and 24 months2*
| DURATION | VYLOY + mFOLFOX6 | PLACEBO + mFOLFOX6 |
|---|---|---|
| At 12 months | 68% | 60% |
| At 24 months | 39% | 28% |
*Estimate based on Kaplan-Meier method.2
In the SPOTLIGHT Phase 3 trial, VYLOY + mFOLFOX6 was evaluated against mFOLFOX6 alone1,2
SPOTLIGHT was a double-blind, randomized, global, multicenter study.1,2
ELIGIBILITY CRITERIA2¶
- CLDN18.2+, HER2-, previously untreated adult patients
- Radiological evaluable disease per RECIST v1.1
- ECOG performance status 0 or 1
- Adequate organ function
SELECT EXCLUSION CRITERIA1,2¶
- Received prior treatment for locally advanced unresectable or metastatic G/GEJ adenocarcinoma
- Complete or partial gastric outlet syndrome
- History of CNS metastases
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.
Safety profile for VYLOY + chemo in SPOTLIGHT1
Adverse reactions reported in ≥15% of patients treated with VYLOY with a difference between arms of ≥5% compared to placebo1
| ADVERSE REACTION | VYLOY with mFOLFOX6 (n=279) | PLACEBO with mFOLFOX6 (n=278) | |||
|---|---|---|---|---|---|
| All Grades (%) | Grade 3-4 (%) | All Grades (%) | Grade 3-4 (%) | ||
| Gastrointestinal disorders | Nausea | 82 | 16 | 61 | 7 |
| Vomiting | 67 | 16 | 36 | 6 | |
| Metabolism and nutrition disorders | Decreased appetite | 47 | 6 | 34 | 3.2 |
| General disorders and administration site conditions | Peripheral edema | 18 | 0.7 | 9 | 0 |
- 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
- Median duration of exposure to VYLOY in combination with mFOLFOX6 was 6.2 months (range: 1 day to 40.9 months)
Laboratory abnormalities (≥15%) in SPOTLIGHT with a difference between arms of ≥5% compared to placebo1
| LABORATORY ABNORMALITY | VYLOY with mFOLFOX6* | PLACEBO with mFOLFOX6* | |||
|---|---|---|---|---|---|
| All Grades (%) | Grade 3-4 (%) | All Grades (%) | Grade 3-4 (%) | ||
| Albumin decreased | 78 | 4.4 | 47 | 1.1 | |
| Potassium decreased | 28 | 11 | 21 | 6 | |
| Glucose decreased | 45 | 0.4 | 35 | 0.4 | |
| Sodium decreased | 29 | 5 | 21 | 2.9 | |
*The denominator used to calculate the rate varied from 271 to 272 based on the number of patients with a baseline value and at least 1 post-treatment value.
Nausea and vomiting occurred more often during the first cycle of treatment1
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.
*The onset day in the onset interval was defined as the date of onset minus the date of first dose plus 1.
VYLOY® (zolbetuximab-clzb) + CAPOX significantly improved progression-free survival (PFS) vs CAPOX alone1
Median PFS was 8.2 months with VYLOY + CAPOX vs 6.8 months with CAPOX alone (HR=0.69 [95% CI: 0.54-0.87]; P=0.0007).1
*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.
Overall survival (OS) was significantly improved with VYLOY + CAPOX vs CAPOX alone1
Median OS was 14.4 months with VYLOY + CAPOX vs 12.2 months with CAPOX alone (HR=0.77 [95% CI: 0.62-0.97]; P=0.0118).1
*Based on Kaplan-Meier estimate.1
Response rates from the GLOW Phase 3 trial
*ORR based on binomial distribution (Clopper-Pearson).1
†ORR and DOR were assessed by IRC per RECIST v1.1.1
DOR=duration of response; ORR=objective response rate.
Progression-free survival and overall survival at 12 and 24 months2
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.
PFS at 12 and 24 months2*
| DURATION | VYLOY + CAPOX | PLACEBO + CAPOX |
|---|---|---|
| At 12 months | 35% | 19% |
| At 24 months | 14% | 7% |
OS at 12 and 24 months2*
| DURATION | VYLOY + CAPOX | PLACEBO + CAPOX |
|---|---|---|
| At 12 months | 58% | 51% |
| At 24 months | 29% | 17% |
*Estimate based on Kaplan-Meier method.2
In the GLOW Phase 3 trial, VYLOY + CAPOX was evaluated against CAPOX alone1,2
GLOW was a double-blind, randomized, global, multicenter study.1,2
ELIGIBILITY CRITERIA2¶
- CLDN18.2+, HER2-, previously untreated adult patients
- Radiological evaluable disease per RECIST v1.1
- ECOG performance status 0 or 1
- Adequate organ function
SELECT EXCLUSION CRITERIA1,2¶
- Received prior treatment for locally advanced unresectable or metastatic G/GEJ adenocarcinoma
- Complete or partial gastric outlet syndrome
- History of CNS metastases
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.2
*Claudin 18.2+ (claudin 18.2 positive) is defined as ≥75% of tumor cells demonstrating moderate to strong membranous CLDN18 staining by IHC.2
†HER2-negative tumor as determined by local or central testing.2
‡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 IRC1.
¶Does not include all patient inclusion and exclusion criteria for the GLOW 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.
Safety profile for VYLOY + chemo in GLOW1
Adverse reactions reported in ≥15% of patients treated with VYLOY with a difference between arms of ≥5% compared to placebo1
| ADVERSE REACTION | VYLOY with CAPOX (n=254) |
PLACEBO with CAPOX (n=249) |
|||
|---|---|---|---|---|---|
| All Grades (%) | Grade 3-4 (%) | All Grades (%) | Grade 3-4 (%) | ||
| Gastrointestinal disorders | Nausea | 69 | 9 | 50 | 2.4 |
| Vomiting | 66 | 12 | 31 | 3.6 | |
| Metabolism and nutrition disorders | Decreased appetite | 41 | 7 | 34 | 1.6 |
| Blood and lymphatic system disorders | Neutropenia | 20 | 7 | 14 | 2.8 |
| Investigations | Weight decreased | 20 | 0.4 | 10 | 0.4 |
- 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
- Other clinically relevant adverse reactions (<15%) in GLOW with a difference between arms of 5% compared to placebo included peripheral edema
- Median duration of exposure to VYLOY in combination with CAPOX was 4.4 months (range: 0.03 to 30.7 months)
Laboratory abnormalities (≥15%) in patients treated with VYLOY in GLOW with a difference between arms of ≥5% compared to placebo1
| LABORATORY ABNORMALITY | VYLOY with CAPOX* |
PLACEBO with CAPOX* |
||
|---|---|---|---|---|
| All Grades (%) | Grade 3-4 (%) | All Grades (%) | Grade 3-4 (%) | |
| Albumin decreased | 66 | 3.8 | 47 | 1.7 |
| Leukocytes decreased | 66 | 6 | 60 | 8 |
| Neutrophils decreased | 76 | 21 | 70 | 14 |
| Glucose decreased | 24 | 0 | 18 | 0 |
*The denominator used to calculate the rate varied from 237 to 238 based on the number of patients with a baseline value and at least 1 post-treatment value.
Nausea and vomiting occurred more often during the first cycle of treatment1
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.
Find out how IHC testing for CLDN18.2+ status is used to determine which patients may be candidates for VYLOY + chemo.*
*Fluoropyrimidine- and platinum-containing chemotherapy.1
IHC=immunohistochemistry.
*Fluoropyrimidine- and platinum-containing chemotherapy.1
IHC=immunohistochemistry.
References:
- VYLOY [package insert]. Northbrook, IL: Astellas Pharma US, Inc.
- Shitara K, Lordick F, Bang YJ, et al. Zolbetuximab plus mFOLFOX6 in patients with CLDN18.2-positive, HER2-negative, untreated, locally advanced unresectable or metastatic gastric or gastro-oesophageal junction adenocarcinoma (SPOTLIGHT): a multicentre, randomised, double-blind, phase 3 trial. Lancet 2023;401(10389):1655-1668. Errata in: Lancet 2023;402(10398):290; Lancet 2024;403(10421):30.
- Supplement to: Shitara K, Lordick F, Bang YJ, et al. Zolbetuximab plus mFOLFOX6 in patients with CLDN18.2-positive, HER2- negative, untreated, locally advanced unresectable or metastatic gastric or gastro-oesophageal junction adenocarcinoma (SPOTLIGHT): a multicentre, randomised, double-blind, Phase 3 trial. Lancet (Epub ahead of print) 04-14-2023.
*Fluoropyrimidine- and platinum-containing chemotherapy.1
IHC=immunohistochemistry.
References:
- VYLOY [package insert]. Northbrook, IL: Astellas Pharma US, Inc.
- Shah MA, Shitara K, Ajani JA, et al. Zolbetuximab plus CAPOX in CLDN18.2-positive gastric or gastroesophageal junction adenocarcinoma: the randomized, phase 3 GLOW trial. Nat Med 2023;29(8):2133-2141.
INDICATION/ IMPORTANT SAFETY INFORMATION
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.
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.
INDICATION/ IMPORTANT SAFETY INFORMATION
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.
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.
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.
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.