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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. 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. 3 Posology Prior to administration 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.

, NK-1 receptor blockers and 5-HT3 receptor blockers, as well as other medicinal products as indicated). 4). Pre-medication with systemic corticosteroids per local treatment guidelines may also be considered particularly before the first infusion of zolbetuximab.

Recommended dose 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. b Until disease progression or unacceptable toxicity.

a. 1). b. Refer to the fluoropyrimidine- or platinum-containing chemotherapy prescribing information regarding the dosing information for chemotherapy. Dose modifications 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.

4 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.

6%). Serious adverse reactions occurred in 45% of patients treated with zolbetuximab. 9%). 3%). 1%). Tabulated list of adverse reactions The frequencies of adverse reactions are based on two phase 2 studies and two phase 3 studies in 631 patients who received at least one dose of zolbetuximab 800 mg/m2 as a loading dose followed by 600 mg/m2 maintenance doses every 3 weeks in combination with fluoropyrimidine- and platinum-containing chemotherapy.

Patients were exposed to zolbetuximab for a median duration of 174 days (range: 1 to 1791 days). Adverse reactions observed during clinical studies are listed in this section by frequency category. Frequency categories are defined as follows: very common (≥1/10); common (≥1/100 to <1/10); uncommon (≥1/1 000 to <1/100); rare (≥1/10 000 to <1/1 000); very rare (<1/10 000); not known (cannot be estimated from the available data).

Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness. Table 4. 6%, respectively. 2%. 3% of patients. 3% of patients. 2% of patients due to drug hypersensitivity. 2%. 5% of patients treated with zolbetuximab in combination with fluoropyrimidine and platinum-containing chemotherapy.

6% of patients. 3% of patients due to an IRR. 9%, respectively. Nausea and vomiting occurred more often during the first cycle of treatment but decreased in incidence with subsequent cycles of treatment. The median time to onset of nausea and vomiting was 1 day each with zolbetuximab in combination with fluoropyrimidine and platinum-containing chemotherapy.

The median duration of nausea and vomiting was 3 days and 1 day, respectively, with zolbetuximab in combination with fluoropyrimidine and platinum-containing chemotherapy. 6%. 5% of patients. 6% of patients. 8% of patients due to vomiting.

Reporting of suspected adverse reactions Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the national reporting system listed in Appendix V.

Traceability In order to improve the traceability of biological medicinal products, the name and the batch number of the administered product should be clearly recorded. 8). Patients should be monitored during and after infusion with zolbetuximab (at least 2 hours, 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).

Hypersensitivity reactions should be managed according to the dose modifications as recommended in Table 2. 8). Patients should be monitored for signs and symptoms of infusion-related reactions 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. Infusion-related reactions should be managed according to the dose modifications as recommended in Table 2. 8). 2). During and after infusion, patients should be monitored and managed using standard of care, including antiemetics or fluid replacement, as clinically indicated.

Nausea and vomiting should be managed according to the dose modifications as recommended in Table 2. Mitigation measures before initiating treatment with zolbetuximab Prior to treatment with zolbetuximab in combination with fluoropyrimidine- and platinum-containing chemotherapy, prescribers should evaluate the individual patient’s risk of gastrointestinal toxicities.

It is important to proactively manage nausea and vomiting to mitigate the potential risk of reduced exposure to zolbetuximab and/or chemotherapy. To prevent nausea and vomiting, pre-treatment with a combination of antiemetics is recommended prior to each infusion of zolbetuximab.

During infusion, it is important to closely monitor patients and manage gastrointestinal toxicities by infusion interruption and/or infusion rate reduction to minimize the risk of severe adverse reactions or early treatment discontinuation.

1.