Formulation and specifications: Injection: 40mg (4ml)/bottle, 100mg (10ml)/bottle
Indications.
1. This product alone is indicated for the treatment of adult patients with EGFR mutation-negative and ALK-negative locally advanced or metastatic NSCLC whose disease has progressed or is intolerable after prior chemotherapy with platinum-containing regimens.
2. This product is used in combination with epilimumab in adult patients with non-surgically resectable, primary non-epithelial malignant pleural mesothelioma.
Key points for rational drug use:
1. Adult patients with locally advanced or metastatic NSCLC with disease progression or intolerability after prior chemotherapy with platinum-containing regimens.
2. Patients must be EGFR-negative and ALK-negative.
3. Navulizumab therapy should be continued as long as clinical benefit is observed until the patient is intolerant and an atypical response is likely to be observed (e.g., temporary tumor enlargement or the appearance of new small lesions during the first few months, followed by tumor shrinkage). If the patient’s clinical symptoms are stable or continue to decrease, even if there is preliminary evidence of disease progression, continued treatment with this product may be considered based on the judgment of overall clinical benefit until disease progression is confirmed.
4. Navulizumab is approved for single-agent use in China based on the CheckMate 078 study at a dose of 3 mg/kg or a fixed dose of 240 mg administered every 2 weeks as a 30-minute infusion. In Europe and the United States, nabolutumab has been approved at a fixed dose of 480 mg every 4 weeks or 240 mg every 2 weeks as a 30-minute infusion based on the PPK study.
The product can be infused directly with 10mg/ml solution or diluted with sodium chloride solution for injection (9mg/ml, 0.9%) or glucose solution for injection (50mg/ml, 5%) at concentrations as low as 1mg/ml. the total infusion volume must not exceed 160ml.
6. The recommended dose in combination with epilimumab for malignant pleural mesothelioma is 360 mg every 3 weeks or 3 mg/kg every 2 weeks by intravenous infusion over 30 minutes, combined with epilimumab 1 mg/kg every 6 weeks by intravenous infusion over 30 minutes. Treatment continues for up to 24 months in patients without disease progression. When used in combination with epilimumab, the product should be infused first, followed by epilimumab on the same day. Use a separate infusion bag and filter for each infusion and flush the infusion line at the end of the infusion.
7. Dosing may be suspended or discontinued depending on the safety and tolerability of the individual patient. Dose increases or decreases are not recommended.
8. The occurrence of grade 4 or recurrent grade 3 adverse reactions and the persistence of grade 2 or 3 adverse reactions despite therapeutic modifications should result in permanent discontinuation of nabumetinumab.
9. No dose adjustment is required in elderly patients (≥65 years).
10. No dose adjustment is required in patients with mild to moderate renal impairment. Limited data are available for patients with severe renal impairment. No dose adjustment is required in patients with mild to moderate hepatic impairment. No studies have been performed in patients with severe hepatic impairment and this product must be used with caution in patients with severe (total bilirubin, ALT or AST > 3 times the upper limit of normal) hepatic impairment.
11. Navulizumab may cause immune-related adverse reactions. Because adverse reactions may occur at any time during or after discontinuation of nabumetumab therapy, patients should be monitored continuously (at least until 5 months after the last dose).
12. For suspected immune-related adverse reactions, adequate evaluation should be performed to confirm the etiology or to exclude other etiologies. Depending on the severity of the adverse reaction, nabumetinumab therapy should be suspended and glucocorticoids administered. If glucocorticoid immunosuppressive therapy is used to treat adverse reactions, a taper to discontinuation is required for at least 1 month after symptoms improve. Rapid dose reduction may cause worsening or recurrence of adverse reactions. If glucocorticosteroids are used but still worsen or do not improve, non-glucocorticoid immunosuppressive therapy should be added.
13. Navulizumab therapy should not be resumed while the patient is receiving immunosuppressive doses of glucocorticosteroids or other immunosuppressive therapy.
14. If any severe, recurrent immune-related adverse reactions and any life-threatening immune-related adverse reactions occur, nabumetinumab therapy must be permanently discontinued.
15. Navulizumab injection contains 0.1 mmol (or 2.5 mg) of sodium per mL and this should be considered when treating patients with controlled sodium intake.
16. Navulizumab is a human monoclonal antibody, and because monoclonal antibodies are not metabolized by CYP450 or other drug-metabolizing enzymes, inhibition or induction of these enzymes by the drugs used in combination is not expected to affect the pharmacokinetic properties of navulizumab.
17. When this product is given in combination with epirimumab, if either drug is suspended, the other drug should be suspended at the same time. If dosing is restarted after suspension, either combination therapy or this product monotherapy should be restarted based on the individual patient’s assessment.
※18. The US FDA approved nabolutumab in combination with epirimizumab for the first-line treatment of tumors with positive PD-L1 expression (defined as ≥1% of tumor cells expressing PD-L1), negative EGFR mutation and ALK-negative, advanced or metastatic NSCLC. This indication is not yet approved in China and may be used with adequate communication with the patient. Navulizumab is administered at 3 mg/kg every 2 weeks, and epirimizumab is administered at 1 mg/kg every 6 weeks. In addition, the US FDA and EU EMA have approved nabritumomab in combination with epirimumab and two cycles of platinum-containing two-drug chemotherapy for the first-line treatment of EGFR mutation-negative and ALK-negative, advanced or metastatic NSCLC, which is not yet approved in China and can be used with adequate communication with patients. Navulizumab is administered at a fixed dose of 360 mg every 3 weeks, and epirimizumab is administered at 1 mg/kg every 6 weeks.