VYLOY

Treatment with Vyloy should be initiated and supervised by a physician experienced in the use of anticancer therapies. 1). Prior to administration If a patient is experiencing nausea and/or vomiting prior to administration of Vyloy, the symptoms should be resolved to Grade ≤1 before administering the first infusion.

4). Recommended dose 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. c.

2). Dose modifications No dose reduction for Vyloy is recommended. Adverse reactions for Vyloy are managed by infusion rate reduction, interruption, and/or discontinuation as presented in Table 2. Table 2. Dose modifications for Vyloy Adverse reaction Severitya Dose modification Adverse reaction Severitya Dose modification Anaphylactic reaction, suspected anaphylaxis, Grade 3 or 4 Immediately stop the infusion and permanently discontinue.

4) Grade 2 • Interrupt the infusion until Grade ≤1, then resume at a reduced infusion rate for the remaining infusion. • For the next infusion, premedicate and administer per the infusion rates in Table 3. Grade 3 or 4 Immediately stop the infusion and permanently discontinue.

4) Grade 2 • Interrupt the infusion until Grade ≤1, then resume at a reduced infusion rate for the remaining infusion. • For the next infusion, premedicate and administer per the infusion rates in Table 3. 4) Grade 2 or 3 • Interrupt the 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 Table 3. Grade 4 Permanently discontinue. 4) Grade 2 or 3 • Interrupt the 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 Table 3.

a. 03) where Grade 1 is mild, Grade 2 is moderate, Grade 3 is severe, Grade 4 is life-threatening. 2). 2). Vyloy has only been evaluated in a limited number of patients with severe renal impairment. 2). Vyloy has only been evaluated in a limited number of patients with moderate hepatic impairment and has not been evaluated in patients with severe hepatic impairment.

Paediatric population The safety and efficacy of Vyloy in the paediatric population have not been established. Method of administration Vyloy is for intravenous use. The recommended dose is administered by intravenous infusion over a minimum of 2 hours.

Vyloy must not be administered as an intravenous push or bolus injection. If Vyloy and fluoropyrimidine- and platinum-containing chemotherapy are administered on the same day, Vyloy must be administered first. To help minimise potential adverse reactions, it is recommended that each infusion should be started at a slower rate than the initially calculated rate for the entire infusion, and gradually increased as tolerated during the course of the infusion (see Table 3).

3 for recommended storage times). Table 3. Infusion rates recommended for each Vyloy infusion Infusion Rate Vyloy dose First 30- 60 minutes Remaining infusion timeb Single loading dose (Cycle 1, Day 1)a 800 mg/m2 100 mg/m2/hr 200-400 mg/m2/hr 600 mg/m2 every 3 weeks 75 mg/m2/hr 150-300 mg/m2/hr or or orMaintenance doses 400 mg/m2 every 2 weeks 50 mg/m2/hr 100-200 mg/m2/hr a.

1). b. In the absence of adverse reactions after 30-60 minutes, the infusion rate can be increased as tolerated. 6.

Summary of the safety profile The safety of Vyloy was evaluated in the integrated safety population from two phase 2 studies (FAST, ILUSTRO) and two phase 3 studies (SPOTLIGHT, GLOW) in 631 patients who received at least one dose of Vyloy 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.

The median duration of exposure to zolbetuximab was 174 days (range: 1 to 1791 days). Serious adverse events occurred in 45% of patients treated with Vyloy and/or fluoropyrimidine and platinum-containing chemotherapy. 9%). 3%). 6%). 8%).

Tabulated list of adverse reactions 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% (10/611)]. 2% (1/611)]. The median time to first onset of anaphylactic reaction or drug hypersensitivity with Vyloy and/or fluoropyrimidine and platinum-containing chemotherapy was 22 days or 113 days, respectively.

5%) permanently discontinued Vyloy and/or fluoropyrimidine and platinum-containing chemotherapy due to anaphylactic reaction. 0%). 2%) due to drug hypersensitivity. 1% (7/611). 5% (3/631)] compared with the placebo in combination with fluoropyrimidine and platinum-containing chemotherapy arm [0% (0/611)].

The median time to first onset of infusion-related reaction with Vyloy in combination with fluoropyrimidine and platinum- containing chemotherapy was 22 days. 6%) patients. 3%) due to an IRR. 8% (225/611)]. 7% (29/611)]. The median time to first onset of nausea or vomiting with Vyloy in combination with fluoropyrimidine and platinum-containing chemotherapy was 1 day or 1 day, respectively.

4%) patients. Vomiting led to […]

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). 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 (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 Table 3, and closely monitor the patient for symptoms and signs of a hypersensitivity reaction.

2). 8). 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 Table 3, and closely monitor the patient for symptoms and signs of an IRR. 2). 8). Nausea and vomiting occurred more often during the first cycle of treatment but decreased in incidence with subsequent cycles of treatment.

2). 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 Table 3, and closely monitor the patient for symptoms and signs of nausea or vomiting. 2). 05 mg of polysorbate 80 in each vial. Polysorbates may cause allergic reactions.

1.