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.
Severe (Grade 3) • Hold infusion immediately. • Promptly treat with appropriate therapy. • Resume infusion at the next scheduled dose at 50% of previous infusion rate once symptoms resolve. • Permanently discontinue for recurrent Grade 3 symptoms.
Life threatening (Grade 4) • Hold infusion immediately. • Promptly treat with appropriate therapy. • Permanently discontinue. 4 Dose modifications for pneumonitis Management of pneumonitis may require treatment discontinuation as described in Table 3.
Table 3. 4) Severity Treatment modification Confirmed Grade ≥ 2 • Permanently discontinue. Missed dose If a patient misses a dose of Ziihera, the scheduled dose should be administered as soon as possible. The administration schedule should be adjusted to maintain a 2-week interval between doses.
Special populations Renal impairment Dose adjustments are not required for patients with mild or moderate renal impairment (eGFR 30 to 89 mL/min estimated using the CKD-EPI). Zanidatamab has not been evaluated in patients with severe renal impairment and patients with end-stage renal disease with or without dialysis.
2). 5 times ULN and any AST). 5 to ≤ 3 ULN and any AST) to severe (total bilirubin > 3 ULN and any AST) hepatic impairment. 2). 2). Paediatric population Children under the age of 18 were not included in the clinical trials. Hence, the safety, efficacy and pharmacokinetics of zanidatamab have not been established in this population.
Method of administration Ziihera is administered by intravenous infusion. It must not be administered by intravenous push or as a rapid single bolus injection. 4 to 6 mg/mL zanidatamab. 6. Table 4. Recommended infusion durations Dose Infusion duration First and Second 120-150 minutes Third and Fourth 90 minutes, if previous infusions were well-tolerated Subsequent 60 minutes, if previous infusions were well-tolerated 5