Source: European Medicines Agency (EU) Revision Year: 2024 Publisher: Astellas Pharma Europe B.V., Sylviusweg 62, 2333 BE Leiden, The Netherlands
Vyloy, 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 (see section 4.2).
Treatment should be prescribed, initiated and supervised by a physician experienced in the use of anti-cancer therapies. Resources for the management of hypersensitivity reactions and/or anaphylactic reactions should be available.
Eligible patients should have CLDN18.2 positive tumour status defined as ≥75% of tumour cells demonstrating moderate to strong membranous CLDN18 immunohistochemical staining, assessed by a CE-marked IVD with the corresponding intended purpose. If the CE-marked IVD is not available, an alternative validated test should be used.
If a patient is experiencing nausea and/or vomiting prior to administration of zolbetuximab, the symptoms should be resolved to Grade ≤1 before administering the first infusion.
Prior to each infusion of zolbetuximab, patients should be pre-medicated with a combination of antiemetics (e.g., NK-1 receptor blockers and 5-HT3 receptor blockers, as well as other medicinal products as indicated).
Pre-medication with a combination of antiemetics is important for the management of nausea and vomiting to prevent early treatment discontinuation of zolbetuximab (see section 4.4). Pre-medication with systemic corticosteroids per local treatment guidelines may also be considered particularly before the first infusion of zolbetuximab.
The recommended dose should be calculated according to body surface area (BSA) for the zolbetuximab loading dose and maintenance doses as provided in Table 1.
Table 1. Recommended zolbetuximab dose based on BSA:
| Single loading dose | Maintenance doses | Duration of therapy |
|---|---|---|
| On Cycle 1, Day 1a, 800 mg/m² intravenously Administer zolbetuximab in combination with fluoropyrimidine- and platinum-containing chemotherapy (see section 5.1).b | Beginning 3 weeks after the single loading dose, 600 mg/m² intravenously every 3 weeks or Beginning 2 weeks after the single loading dose, 400 mg/m² intravenously every 2 weeks Administer zolbetuximab in combination with fluoropyrimidine- and platinum-containing chemotherapy (see section 5.1).b | Until disease progression or unacceptable toxicity. |
a The cycle duration of zolbetuximab is determined based on the respective chemotherapy backbone (see section 5.1).
b Refer to the fluoropyrimidine- or platinum-containing chemotherapy prescribing information regarding the dosing information for chemotherapy.
No dose reduction for zolbetuximab is recommended. Adverse reactions for zolbetuximab are managed by infusion rate reduction, interruption, and/or discontinuation as presented in Table 2.
Table 2. Dose modifications for zolbetuximab:
| Adverse reaction | Severitya | Dose modification |
|---|---|---|
| Hypersensitivity reactions | Anaphylactic reaction, suspected anaphylaxis, Grade 3 or 4 | Immediately stop the infusion and permanently discontinue. |
| Grade 2 | Interrupt the infusion until Grade ≤1, then resume at a reduced infusion rateb for the remaining infusion. For the next infusion, premedicate with antihistamines and administer per the infusion rates in Table 3. | |
| Infusion related reaction | Grade 3 or 4 | Immediately stop the infusion and permanently discontinue. |
| Grade 2 | Interrupt the infusion until Grade ≤1, then resume at a reduced infusion rateb for the remaining infusion. For the next infusion, premedicate with antihistamines and administer per the infusion rates in Table 3. | |
| Nausea | Grade 2 or 3 | Interrupt the infusion until Grade ≤1, then resume at a reduced infusion rateb for the remaining infusion. For the next infusion, administer per the infusion rates in Table 3. |
| Vomiting | Grade 4 | Permanently discontinue. |
| Grade 2 or 3 | Interrupt the infusion until Grade ≤1, then resume at a reduced infusion rateb for the remaining infusion. For the next infusion, administer per the infusion rates in Table 3. |
a Toxicity was graded per National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.03 (NCI-CTCAE v4.03) where Grade 1 is mild, Grade 2 is moderate, Grade 3 is severe, Grade 4 is life-threatening.
b Reduced infusion rate should be determined per physician’s clinical judgment based on patient tolerability, severity of toxicity, and previously tolerated infusion rate (see section 4.4 for patient monitoring recommendations).
No dose adjustment is required in patients ≥65 years of age (see section 5.2). Data for patients aged 75 years and older who received zolbetuximab are limited.
No dose adjustment is required in patients with mild (creatinine clearance [CrCL] ≥60 to <90 mL/min) or moderate (CrCL ≥30 to <60 mL/min) renal impairment. No dose recommendation has been established in patients with severe renal impairment (CrCL ≥15 to <30 mL/min) (see section 5.2).
No dose adjustment is required in patients with mild hepatic impairment (total bilirubin [TB] ≤ upper limit of normal [ULN] and aspartate aminotransferase [AST] >ULN, or TB >1 to 1.5 × ULN and any AST). No dose recommendation has been established in patients with moderate (TB >1.5 to 3 × ULN and any AST) or severe (TB >3 to 10 × ULN and any AST) hepatic impairment (see section 5.2).
There is no relevant use of zolbetuximab in the paediatric population in the treatment of gastric or gastro-oesophageal junction adenocarcinoma.
Zolbetuximab is for intravenous use. The recommended dose is administered by intravenous infusion over a minimum of 2 hours. The medicinal product must not be administered as an intravenous push or bolus injection.
If zolbetuximab and fluoropyrimidine- and platinum-containing chemotherapy are administered on the same day, zolbetuximab must be administered first.
To help minimise potential adverse reactions, it is recommended that each infusion is started at a slower rate for 30-60 minutes, and gradually increased as tolerated during the course of the infusion (see Table 3).
If the infusion time exceeds the recommended storage time at room temperature (≤25°C for 6 hours from end of preparation of infusion solution), the infusion bag must be discarded and a new infusion bag prepared to continue the infusion (see section 6.3 for recommended storage times).
Table 3. Infusion rates recommended for each zolbetuximab infusion:
| Zolbetuximab dose | Infusion rate | ||
|---|---|---|---|
| First 30-60 minutes | Remaining infusion timeb | ||
| Single loading dose (Cycle 1, Day 1)a | 800 mg/m² | 75 mg/m²/hr | 150-300 mg/m²/hr |
| Maintenance doses | 600 mg/m² every 3 weeks Or 400 mg/m² every 2 weeks | 75 mg/m²/hr or 50 mg/m²/hr | 150-300 mg/m²/hr or 100-200 mg/m²/hr |
a The cycle duration of zolbetuximab is determined based on the respective chemotherapy backbone (see section 5.1).
b In the absence of adverse reactions after 30-60 minutes, the infusion rate can be increased as tolerated.
For instructions on reconstitution and dilution of the medicinal product before administration, see section 6.6.
In case of overdose, the patient should be closely monitored for adverse reactions, and supportive treatment should be administered, as appropriate.
Unopened vial:
4 years.
Reconstituted solution in the vial:
Reconstituted vials may be stored at room temperature (≤25°C) for up to 5 hours. Do not freeze them nor expose them to direct sunlight. Discard unused vials with reconstituted solution beyond the recommended storage time.
Diluted solution in the infusion bag:
From a microbiological point of view, the diluted solution in the bag should be administered immediately. If not administered immediately, the prepared infusion bag should be stored:
Do not expose to direct sunlight. Discard unused prepared infusion bags beyond the recommended storage time.
Store in a refrigerator (2ºC–8ºC).
Do not freeze.
Store in the original package in order to protect from light.
For storage conditions after reconstitution and dilution of the medicinal product, see section 6.3.
20 mL Type I glass vial with European blow-back feature, grey bromobutyl rubber stopper with ethylene tetrafluoroethylene film, and aluminum seal with a green cap.
Pack sizes: one carton containing 1 or 3 vials.
Not all pack sizes may be marketed.
Reconstitution in single-dose vial:
Dilution in infusion bag:
Administration:
No incompatibilities have been observed with closed system transfer device composed of PP, PE, stainless steel, silicone (rubber/oil/resin), polyisoprene, PVC or with plasticizer [TOTM], acrylonitrile-butadiene-styrene (ABS) copolymer, methyl methacrylate-ABS copolymer, thermoplastic elastomer, polytetrafluoroethylene, polycarbonate, PES, acrylic copolymer, polybutylene terephthalate, PB, or EVA copolymer.
No incompatibilities have been observed with central port composed of silicone rubber, titanium alloy or PVC with plasticizer [TOTM].
Disposal:
Any unused medicinal product or waste material should be disposed of in accordance with local requirements.
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