Tizveni

Tizveni treatment must be initiated and supervised by physicians experienced in the treatment of cancer. 1). Posology Tizveni monotherapy The recommended dose of Tizveni is 200 mg administered by intravenous infusion once every 3 weeks.

Tizveni combination therapy 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 pre- medication for the prevention of chemotherapy-related adverse reactions.

Duration of treatment Patients should be treated with Tizveni until disease progression or unacceptable toxicity. 4) 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

Summary of the safety profile The safety of tislelizumab as monotherapy is based on pooled data in 1 534 patients across multiple tumour types who received 200 mg tislelizumab every 3 weeks. 9%). 0%). 2% of patients experienced adverse reactions leading to death.

07%). 2% were exposed for longer than 12 months. The safety of tislelizumab given in combination with chemotherapy is based on data in 497 patients with NSCLC. 4%). 2%). 6% of patients experienced adverse reactions leading to death. 20%).

8% were exposed for longer than 12 months. Tabulated list of adverse reactions Adverse reactions reported in the pooled dataset for patients treated with Tizveni monotherapy (n = 1 534) and in combination with chemotherapy (n = 497) are presented in Table 2.

Adverse reactions are listed according to system organ class in MedDRA. Within each system organ class, the adverse reactions are presented in decreasing frequency. The corresponding frequency category for each adverse reaction is 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 available data).

Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness. Table 2 Adverse reactions with Tizveni as monotherapy (n = 1 534) and in combination with chemotherapy (n = 497) Tislelizumab monotherapy n = 1 534 Tislelizumab plus chemotherapy n = 497 Adverse reactions Frequency category (All grades) Frequency category (All grades) Infections and infestations Pneumonia1 Common* Very common* Blood and lymphatic system disorders Anaemia2 Very common Very common Thrombocytopenia3 Common* Very common Neutropenia4 Common Very common Lymphopenia5 Common Very commonMedicinal product no longer authorised 11 Endocrine disorders Hypothyroidism6 Very common Very common Hyperthyroidism7 Common Very common Thyroiditis8 Common Uncommon Adrenal insufficiency9 Uncommon - Hypophysitis10 Rare - Metabolism and nutrition disorders Hyperglycaemia11 Common Very common Hyponatraemia12 Common Very common Hypokalaemia13 Common Very common* Diabetes mellitus14 Uncommon Common Nervous system disorders Guillain-Barré syndrome - Uncommon Eye disorders Uveitis15 Uncommon - Cardiac disorders Myocarditis16 Uncommon Common* Pericarditis Rare - Vascular disorders Hypertension17 Common Common Respiratory, thoracic and mediastinal disorders Cough Very common Very common Dyspnoea Common* Very common* Pneumonitis18 Common* Very common* Gastrointestinal disorders Nausea Common Very common Diarrhoea19 Common Very common Stomatitis20 Common Common Pancreatitis21 Uncommon Uncommon Colitis22 Uncommon Common Hepatobiliary disorders Hepatitis23 Common* Common Skin and subcutaneous tissue disorders Rash24 Very common Very common Pruritus Very common Common Severe skin reactions25 Rare - Musculoskeletal and connective tissue disorders Arthralgia Common Very common Myalgia Common Common Myositis26 Uncommon Uncommon Arthritis27 Uncommon Common Renal and urinary disorders Nephritis28 Uncommon Uncommon General disorders and administration site conditions Fatigue29 Very common Very common Decreased appetite Very common* Very common Investigations Aspartate aminotransferase increased Very common Very common Alanine aminotransferase increased Very common Very common Blood bilirubin increased30 Very common Very common Blood alkaline phosphatase increased Common Very common Blood creatinine increased Common Very commonMedicinal product no longer authorised 12 Injury, poisoning and procedural complications Infusion-related reaction31 Uncommon Common 1 Pneumonia includes preferred terms (PTs) of pneumonia, lower respiratory tract infection, lower respiratory tract infection bacterial, pneumonia bacterial, pneumonia fungal and pneumocystis jirovecii pneumonia.

4. 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 discontinueMedicinal product no longer authorised 4 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.

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.

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.

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 discontinue3Medicinal product no longer authorised 5 Other adverse drug reactions Infusion-related reactions Grade 1 Consider pre-medication for prophylaxis of subsequent infusion reactions.

Medicinal product no longer authorised 6