Source: European Medicines Agency (EU) Revision Year: 2024 Publisher: Beigene Ireland Limited, 10 Earlsfort Terrace, Dublin 2, D02 T380, Ireland, Tel. +353 1 566 7660, E-mail: bg.ireland@beigene.com
Tizveni in combination with pemetrexed and platinum-containing chemotherapy is indicated for the first-line treatment of adult patients with non-squamous non-small cell lung cancer whose tumours have PD-L1 expression on ≥50% of tumour cells with no EGFR or ALK positive mutations and who have:
Tizveni in combination with carboplatin and either paclitaxel or nab-paclitaxel is indicated for the first-line treatment of adult patients with squamous non-small cell lung cancer who have:
Tizveni as monotherapy is indicated for the treatment of adult patients with locally advanced or metastatic non-small cell lung cancer after prior platinum-based therapy. Patients with EGFR mutant or ALK positive NSCLC should also have received targeted therapies before receiving tislelizumab.
Tizveni treatment must be initiated and supervised by physicians experienced in the treatment of cancer.
Patients with first-line non-squamous non-small cell lung cancer should be evaluated for treatment based on the tumour cell expression of PD-L1 confirmed by a certified in vitro diagnostic medical device test (see section 5.1).
The recommended dose of Tizveni is 200 mg administered by intravenous infusion once every 3 weeks.
The recommended dose of Tizveni is 200 mg administered by intravenous infusion once every 3 weeks, in combination with chemotherapy.
When Tizveni and chemotherapy are administered on the same day, Tizveni should be administered before chemotherapy. The Summary of Product Characteristics (SmPC) for the chemotherapy product should be referred to for dosing as well as for recommendations on corticosteroid use as premedication for the prevention of chemotherapy-related adverse reactions.
Patients should be treated with Tizveni until disease progression or unacceptable toxicity.
No dose reductions of Tizveni as monotherapy or in combination therapy are recommended. Tizveni should be withheld or discontinued as described in Table 1.
Detailed guidelines for the management of immune-related adverse reactions are described in section 4.4.
Table 1. Recommended treatment modifications for Tizveni:
| Immune-related adverse reaction | Severity1 | Tizveni treatment modification |
|---|---|---|
| Pneumonitis | Grade 2 | Withhold2,3 |
| Recurrent grade 2; grade 3 or 4 | Permanently discontinue3 | |
| Hepatitis | ALT or AST >3 to 8 x ULN or total bilirubin >1.5 to 3 x ULN | Withhold2,3 |
| ALT or AST >8 x ULN or total bilirubin >3 x ULN | Permanently discontinue3 | |
| Rash | Grade 3 | Withhold2,3 |
| Grade 4 | Permanently discontinue3 | |
| Severe cutaneous adverse reactions (SCARs) | Suspected SCARs, including SJS or TEN | Withhold2,3 For suspected SJS or TEN, do not resume unless SJS/TEN has been ruled out in consultation with appropriate specialist(s). |
| Confirmed SCARs, including SJS or TEN | Permanently discontinue | |
| Colitis | Grade 2 or 3 | Withold2,3 |
| Recurrent grade 3; grade 4 | Permanently discontinue3 | |
| Myositis/rhabdomyolysis | Grade 2 or 3 | Withhold2,3 |
| Recurrent grade 3; grade 4 | Permanently discontinue3 | |
| Hypothyroidism | Grade 2, 3 or 4 | Hypothyroidism may be managed with replacement therapy without treatment interruption. |
| Hyperthyroidism | Grade 3 or 4 | Withhold2 For grade 3 or 4 that has improved to grade ≤2 and is controlled with anti-thyroid therapy, if indicated continuation of Tizveni may be considered after corticosteroid taper. Otherwise, treatment should be discontinued. |
| Adrenal insufficiency | Grade 2 | Consider withholding treatment until controlled by HRT. |
| Grade 3 or 4 | Withhold3 For grade 3 or 4 that has improved to grade ≤2 and is controlled with HRT, if indicated continuation of Tizveni may be considered after corticosteroid taper. Otherwise, treatment should be discontinued.3 | |
| Hypophysitis | Grade 2 | Consider withholding treatment until controlled by HRT. |
| Grade 3 or 4 | Withhold2,3 For grade 3 or 4 that has improved to grade ≤2 and is controlled with HRT, if indicated continuation of Tizveni may be considered after corticosteroid taper. Otherwise, treatment should be discontinued.3 | |
| Type 1 diabetes mellitus | Type 1 diabetes mellitus associated with grade ≥3 hyperglycaemia (glucose >250 mg/dl or >13.9 mmol/l) or associated with ketoacidosis | Withhold For grade 3 or 4 that has improved to grade ≤2 with insulin therapy, if indicated continuation of Tizveni may be considered once metabolic control is achieved. Otherwise, treatment should be discontinued. |
| Nephritis with renal dysfunction | Grade 2 (creatinine >1.5 to 3 x baseline or >1.5 to 3 x ULN) | Withhold2,3 |
| Grade 3 (creatinine >3 x baseline or >3 to 6 x ULN) or grade 4 (creatinine >6 x ULN) | Permanently discontinue3 | |
| Myocarditis | Grade 2, 3 or 4 | Permanently discontinue3 |
| Neurological toxicities | Grade 2 | Withhold2,3 |
| Grade 3 or 4 | Permanently discontinue3 | |
| Pancreatitis | Grade 3 pancreatitis or grade 3 or 4 serum amylase or lipase levels increased (>2 x ULN) | Withhold2,3 |
| Grade 4 | Permanently discontinue3 | |
| Other immune-related adverse reactions | Grade 3 | Withhold2,3 |
| Recurrent grade 3; grade 4 | Permanently discontinue3 | |
| Infusion-related reactions | Grade 1 | Consider pre-medication for prophylaxis of subsequent infusion reactions. Slow the rate of infusion by 50%. |
| Grade 2 | Interrupt infusion. Resume infusion if resolved or decreased to grade 1, and slow rate of infusion by 50%. | |
| Grade 3 or 4 | Permanently discontinue |
ALT = alanine aminotransferase, AST = aspartate aminotransferase, HRT = hormone replacement therapy, SJS = Stevens-Johnson syndrome, TEN = toxic epidermal necrolysis, ULN = upper limit normal
1 Toxicity grades are in accordance with National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.0 (NCI-CTCAE v4.0). Hypophysitis grade is in accordance with NCI-CTCAE v5.0.
2 Resume in patients with complete or partial resolution (grade 0 to 1) after corticosteroid taper over at least 1 month. Permanently discontinue if no complete or partial resolution within 12 weeks of initiating corticosteroids or inability to reduce prednisone to ≤10 mg/day (or equivalent) within 12 weeks of initiating corticosteroids.
3 Initial dose of 1 to 2 mg/kg/day prednisone or equivalent followed by a taper to ≤10 mg/day (or equivalent) over at least 1 month is recommended, except for pneumonitis, where initial dose of 2 to 4 mg/kg/day is recommended.
The safety and efficacy of Tizveni in patients aged below 18 years have not been established. No data are available.
No dose adjustment is needed for patients aged ≥65 years (see section 4.8).
No dose adjustment is needed for patients with mild or moderate renal impairment. Data from patients with severe renal impairment are too limited to make dosing recommendations for this population (see section 5.2).
No dose adjustment is needed for patients with mild or moderate hepatic impairment. Data from patients with severe hepatic impairment are too limited to make dosing recommendations for this population (see section 5.2).
Tizveni is for intravenous use only. It is to be administered as an infusion and must not be administered as an intravenous push or single bolus injection. For instructions on dilution of the medicinal product before administration, see section 6.6.
The first infusion should be administered over a period of 60 minutes. If this is well tolerated, the subsequent infusions may be administered over a period of 30 minutes. The infusion should be given via an intravenous line containing a sterile, non-pyrogenic, low-protein-binding 0.2 or 0.22 micron in-line or add-on filter.
Other medicinal products must not be mixed or co-administered through the same infusion line.
There is no information on overdose with tislelizumab. In case of overdose, patients should be closely monitored for signs or symptoms of adverse drug reactions, and appropriate symptomatic treatment instituted immediately.
Unopened vial:
3 years.
After opening:
Once opened, the medicinal product should be diluted and infused immediately (see section 6.6 for instructions on dilution of the medicinal product before administration).
After preparation of solution for infusion:
Tizveni does not contain a preservative. Chemical and physical in-use stability has been demonstrated for 24 hours at 2°C to 8°C. The 24 hours include storage of the diluted solution under refrigeration (2°C to 8°C) for no more than 20 hours, time required for returning to room temperature (25°C or below) and time to complete the infusion within 4 hours.
From a microbiological point of view, unless the method of dilution precludes the risk of microbial contamination, the product should be used immediately.
If not used immediately, in-use storage times and conditions are the responsibility of the user. The diluted solution must not be frozen.
Store in a refrigerator (2°C-8°C).
Do not freeze.
Store in the original carton in order to protect from light.
For storage conditions after dilution of the medicinal product, see section 6.3.
10 ml of Tizveni concentrate is provided in a clear Type 1 glass vial, with a grey chlorobutyl stopper with FluroTec coating and seal cap with a flip-off button.
Tizveni is available in unit packs containing 1 vial and in multipacks containing 2 (2 packs of 1) vials.
The diluted solution for infusion should be prepared by a healthcare professional using aseptic technique.
Preparation of solution for infusion:
Administration:
Disposal:
Any unused medicinal product or waste material should be disposed of in accordance with local requirements.
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