VYLOY™ (zolbetuximab), in combination with fluoropyrimidine- and platinum-containing chemotherapy, is indicated for the first-line treatment of adult patients with locally advanced unresectable or metastatic HER2-negative gastric or gastro-oesophageal junction (GEJ) adenocarcinoma whose tumours are Claudin (CLDN) 18.2 positive
Hypersensitivity reactions in patients treated with VYLOY in combination with fluoropyrimidine and platinum-containing chemotherapy during clinical studies were characterized by anaphylactic reaction or drug hypersensitivity. Monitor patients during and after infusion with VYLOY (at least 2 hours, or longer if clinically indicated) for hypersensitivity reactions with symptoms and signs that are highly suggestive of anaphylaxis (e.g., urticaria, repetitive cough, wheeze and throat tightness/change in voice). If an anaphylactic reaction occurs, administration of VYLOY should be immediately and permanently discontinued and appropriate medical therapy administered.
For any Grade 3 or 4 hypersensitivity reaction or hypersensitivity reaction with features of anaphylaxis, administration of VYLOY should be immediately and permanently discontinued and appropriate medical therapy instituted based on the type of reaction.
For any Grade 2 hypersensitivity reaction, interrupt the VYLOY infusion until Grade ≤1, then resume the infusion at a reduced infusion rate for the remaining infusion. Pre-medicate the patient with antihistamines for the next infusion, administer per the infusion rates in the Singapore Approved Package Insert, and closely monitor the patient for symptoms and signs of a hypersensitivity reaction. The infusion rate may be gradually increased as tolerated.
Infusion-related reaction (IRR) has occurred during clinical studies with VYLOY in combination with fluoropyrimidine and platinum-containing chemotherapy. Monitor patients for signs and symptoms of infusion-related reaction including nausea, vomiting, abdominal pain, salivary hypersecretion, pyrexia, chest discomfort, chills, back pain, cough and hypertension. These signs and symptoms are usually reversible with the interruption of the infusion. For Grade 3 or 4 IRRs, administration of VYLOY should be immediately and permanently discontinued and appropriate medical therapy instituted.
For Grade 2 IRRs, interrupt the VYLOY infusion until Grade ≤1, then resume the infusion at a reduced infusion rate for the remaining infusion. Pre-medicate the patient with antihistamines for the next infusion, administer per the infusion rates in the Singapore Approved Package Insert, and closely monitor the patient for symptoms and signs of an IRR. The infusion rate may be gradually increased as tolerated.
During clinical studies, nausea and vomiting were the most frequently observed gastrointestinal (GI) adverse reactions with VYLOY in combination with fluoropyrimidine and platinum-containing chemotherapy treatment.
Nausea and vomiting occurred more often during the first cycle of treatment but decreased in incidence with subsequent cycles of treatment. To prevent nausea and vomiting, pretreatment with a combination of antiemetics is recommended prior to each infusion of VYLOY. During and after infusion, patients should be monitored and managed using standard of care, including antiemetics or fluid replacement, as clinically indicated.
For Grade 4 vomiting, permanently discontinue treatment with VYLOY.
For Grade 2 or 3 nausea or vomiting, interrupt the VYLOY infusion until Grade ≤1, then resume at a reduced infusion rate for the remaining infusion. For the next infusion, administer per the infusion rates in the Singapore Approved Package Insert, and closely monitor the patient for symptoms and signs of nausea or vomiting. The infusion rate may be gradually increased as tolerated.
Serious upper gastrointestinal (GI) haemorrhage has been observed in patients receiving VYLOY in combination with fluoropyrimidine and platinum-containing chemotherapy. In the clinical studies, serious upper GI haemorrhage occurred more frequently in patients receiving zolbetuximab in combination with fluoropyrimidine and platinum-containing chemotherapy [1.0% (6/631)) in comparison with patients receiving placebo in combination with fluoropyrimidine and platinum-containing chemotherapy [0.2% (1/611)]. Monitor patients for signs and symptoms of upper GI haemorrhage during treatment. Promptly evaluate and treat any suspected upper GI haemorrhage.
One event of PRES has been reported in a patient. This is a rare reversible, neurological disorder that can present with rapidly evolving symptoms including seizure, headache, confusion, visual and neurological disturbances, with or without associated hypertension and altered mental status. If PRES is suspected, it should be confirmed by brain imaging, preferably magnetic resonance imaging (MRI). Discontinuation of zolbetuximab treatment in patients who develop PRES is recommended.
PROGRESSION-FREE SURVIVAL
In CLDN18.2+, HER2-, locally advanced unresectable or mG/GEJ cancer (vs placebo + mFOLFOX6)
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
PROGRESSION-FREE SURVIVAL (PRIMARY ENDPOINT)1*
PROGRESSION-FREE SURVIVAL (PRIMARY ENDPOINT)1*
Sustained benefits in PFS were also seen at 12, 18, and 24 months (vs mFOLFOX6 alone)1
*PFS was assessed per RECIST v1.1 by independent review committee.1
CI=confidence interval; HER2=human epidermal growth factor 2; HR=hazard ratio; mG/GEJ=metastatic gastric/gastro-oesophageal junction.
Sustained benefits in PFS were also seen at 12, 18, and 24 months (vs mFOLFOX6 alone)1
*PFS was assessed per RECIST v1.1 by independent review committee.1
CI=confidence interval; HER2=human epidermal growth factor 2; HR=hazard ratio; mG/GEJ=metastatic gastric/gastro-oesophageal junction.
Overall survival (OS) significantly improved with first-line VYLOY + mFOLFOX61
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
OVERALL SURVIVAL (SECONDARY ENDPOINT)1
VYLOY + mFOLFOX6 demonstrated a higher complete response rate (7%) vs mFOLFOX6 alone (4%).2
OBJECTIVE RESPONSE RATE (SECONDARY ENDPOINT)2†
Median duration of response (mDOR) was similar across treatment arms. (9.0 months with VYLOY + mFOLFOX6 vs 8.1 months with mFOLFOX6 alone).2
MEDIAN DURATION OF RESPONSE (SECONDARY ENDPOINT)2‡
*Assessed in the full analysis set, which comprised all randomised patients.
†ORR was assessed by Independent Review Committee (IRC) per RECIST v1.1.2
‡DOR was assessed by IRC per RECIST v1.1.2
DOR=duration of response; ORR=objective response rate; RECIST=Response Evaluation Criteria in Solid Tumours.
Eligibility Criteria2¶
SELECT Exclusion Criteria1,2¶
*Tumour expresses CLDN18.2 in ≥75% of tumour cells demonstrating moderate to strong membranous staining as determined by central IHC testing.2
†HER2-negative tumour as determined by local or central testing on a gastric or GEJ tumour specimen.2
‡No prior systemic chemotherapy.2
§VYLOY was administered at a loading dose of 800 mg/m2 IV on Cycle 1 Day 1 followed by 600 mg/m2 IV every 3 weeks. Additionally, 12 treatments of mFOLFOX6 were administered over 4 cycles (42 days per cycle) on Days 1, 15, and 29. After 12 mFOLFOX6 treatments, subjects continued to receive fluorouracil (5-FU) and folinic acid at the investigator’s discretion until the subject met study treatment discontinuation criteria. Patients were allowed to continue treatment with VYLOY, 5-fluorouracil and folinic acid (leucovorin or local equivalent) at the discretion of the investigator, until disease progression, development of toxic effects, start of another anticancer treatment, or other discontinuation criteria were met, as specified in the protocol.1,2
||Placebo was administered on Cycle 1 Day 1 and every 3 weeks thereafter. Additionally, 12 treatments of mFOLFOX6 were administered over 4 cycles (42 days per cycle) on Days 1, 15, and 29. After 12 mFOLFOX6 treatments, subjects continued to receive fluorouracil (5-FU) and folinic acid at the investigator’s discretion until the subject met study treatment discontinuation criteria. Patients were allowed to continue treatment with VYLOY, 5-fluorouracil and folinic acid (leucovorin or local equivalent) at the discretion of the investigator, until disease progression, development of toxic effects, start of another anticancer treatment, or other discontinuation criteria were met, as specified in the protocol.1,2
¶Does not include all patient inclusion and exclusion criteria for the SPOTLIGHT trial.1,2
#Congestive heart failure (defined as New York Heart Association Class III or IV), history of significant ventricular arrhythmias, QTc interval >450 msec for males; >470 msec for females.1
CLDN18.2=Claudin18.2; CNS=central nervous system; ECOG=Eastern Cooperative Oncology Group; G/GEJ=gastric/gastro-oesophageal junction; HER2=human epidermal growth factor receptor 2; HIV=human immunodeficiency virus; QTc=heart rate—corrected QT interval; RECIST=Response Evaluation Criteria in Solid Tumours.
OVERALL SURVIVAL (SECONDARY ENDPOINT)1
OS benefits were also sustained at 12, 18, and 24 months (vs mFOLFOX6 alone)1
OBJECTIVE RESPONSE RATE (SECONDARY ENDPOINT)2†
MEDIAN DURATION OF RESPONSE (SECONDARY ENDPOINT)2‡
In the SPOTLIGHT Phase 3 trial, VYLOY + mFOLFOX6 were evaluated against mFOLFOX6 alone1
SPOTLIGHT patient population1
Adverse reactions reported in ≥15% of patients1
SPOTLIGHT: Safety data
Find out how IHC testing for CLDN18.2 helps identify patients who may be candidates for VYLOY + chemotherapy.
IHC=immunohistochemistry.
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