Ziihera

Ziihera must be initiated by a physician experienced in the diagnosis and treatment of patients with biliary tract cancer. It must be administered by a qualified healthcare professional, with appropriate resuscitation equipment available.

Patient selection Patients treated with Ziihera for BTC should have documented HER2-positive tumour status, defined as a score of 3 + by immunohistochemistry (IHC) assessed by a CE-marked in vitro diagnostic (IVD) medical device with the corresponding intended purpose.

If a CE-marked IVD is not available, an alternate validated test should be used. Posology The recommended dose of Ziihera is 20 mg/kg, administered as an intravenous infusion every 2 weeks (every 14 days) until disease progression or unacceptable toxicity.

For duration of infusion, see Table 4. 3 Premedications Premedication should be administered 30 to 60 minutes prior to each infusion to prevent potential infusion related reaction. 4). Dose modifications for left ventricular dysfunction Left ventricular function must be assessed at baseline and at regular intervals during treatment.

The recommendations on dose modifications in the event of left ventricular ejection fraction (LVEF) decrease are indicated in Table 1. Table 1. 4) Severity Treatment modification Absolute decrease of ≥ 16% points in LVEF from pre- treatment baseline • Withhold treatment for at least 4 weeks.

• Repeat LVEF assessment within 4 weeks. • Resume treatment within 4 to 8 weeks, if LVEF returns to normal limits and the absolute decrease is ≤ 15% points from baseline. • If LVEF has not recovered to within 15% points from baseline, permanently discontinue.

LVEF value below 50% and absolute decrease of ≥ 10% points below pre-treatment baseline Dose modifications for infusion related reactions Management of infusion related reaction (IRRs) may require reduced infusion rate, dose interruption, or treatment discontinuation as described in Table 2.

Table 2. 8) Severity Treatment modification Mild (Grade 1) • Reduce infusion rate by 50%. • Subsequent infusions should start at this reduced rate. • Infusion rate for subsequent infusions may be increased gradually to the rate prior to symptoms, as tolerated.

Moderate (Grade 2) • Hold infusion immediately. • Treat with appropriate therapy. • Resume infusion at 50% of previous infusion rate once symptoms resolve. • Infusion rate for subsequent infusions may be increased gradually to the rate prior to symptoms, as tolerated.

Summary of the safety profile The pooled safety population of Ziihera reflects exposure in 233 patients who were administered Ziihera 20 mg/kg intravenously as a single agent in two single-arm trials. Among 233 patients who 7 received Ziihera, 39% were exposed for 6 months or longer, and 17% were exposed for greater than one year.

2% of patients. 3%). 5%). The safety of Ziihera in adult patients with BTC (N=87) was evaluated in Study 203, an open-label, multi-cohort, multicenter trial. 1% of patients. 3%). 1%). Tabulated list of adverse reactions Unless otherwise stated, the frequencies of adverse reactions are based on all-cause adverse event frequencies identified in 233 patients exposed to Ziihera at 20 mg/kg administered intravenously as a single agent in two single-arm trials.

Frequencies are defined as: 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

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. Embryo-foetal toxicity, pregnancy and contraception Based on the mechanism of action, zanidatamab may cause foetal harm when administered to a pregnant woman.

6). Patients should be advised to avoid becoming pregnant while receiving Ziihera. A pregnancy test should be performed before initiating treatment to exclude pregnancy. 6). Left ventricular dysfunction Decreases in LVEF have been reported with medicinal products that block HER2 activity, including zanidatamab.

LVEF should be assessed prior to initiation of Ziihera by echocardiogram or multigated acquisition (MUGA) scan and at regular intervals during treatment to ensure that LVEF is within normal limits. 2). Zanidatamab has not been studied in patients with a pre-treatment LVEF value of < 50%; history of myocardial infarction or unstable angina within 6 months; troponin levels consistent with myocardial infarction, or clinically significant cardiac disease such as ventricular arrhythmia requiring therapy, uncontrolled hypertension, or any history of symptomatic congestive heart failure (CHF).

8). 2). Patients should be monitored for signs and symptoms of IRRs during administration and as clinically indicated after completion of infusion. 2). Pneumonitis Pneumonitis has been reported with medicinal products that block HER2 activity, including Ziihera.

4% of 233 patients treated with Ziihera 20 mg/kg intravenously as a single agent in clinical studies. Patients should be monitored for signs and symptoms of pneumonitis. 2). Excipients with known effect Sodium This medicinal product contains less than 1 mmol sodium (23 mg) per dose, that is to say essentially ‘sodium-free’.

105 mg/mL. Polysorbates may cause allergic reactions.

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