TEVIMBRA

Tevimbra treatment must be initiated and supervised by physicians experienced in the treatment of cancer. PD-L1 testing If specified in the indication, patient selection for treatment with Tevimbra based on the tumour expression of PD-L1 should be assessed by a CE-marked IVD with the corresponding intended purpose.

1). Posology Tevimbra monotherapy The recommended dose of Tevimbra is either 200 mg once every 3 weeks or 400 mg once every 6 weeks administered by intravenous infusion. For resectable NSCLC, during the adjuvant treatment phase, the recommended dose of Tevimbra is 400 mg administered by intravenous infusion once every 6 weeks.

Tevimbra combination therapy The recommended dose of Tevimbra is either 200 mg once every 3 weeks or 400 mg once every 6 weeks administered by intravenous infusion, in combination with chemotherapy. When Tevimbra and chemotherapy are administered on the same day, Tevimbra 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.

1). For the neoadjuvant and adjuvant treatment of resectable NSCLC, patients should be treated with neoadjuvant Tevimbra (200 mg every 3 weeks) in combination with chemotherapy for 3 or 4 cycles or until disease progression that precludes definitive surgery or unacceptable toxicity, followed by adjuvant treatment with Tevimbra (400 mg every 6 weeks) as monotherapy for up to 8 cycles or until disease recurrence, metastasis, or unacceptable toxicity.

4) Dose reductions of Tevimbra as monotherapy or in combination therapy are not recommended. Tevimbra should be withheld or discontinued based on safety and tolerability as described in Table 1. Detailed guidelines for the management of immune-related adverse reactions are described in section

The safety of tislelizumab as monotherapy is based on pooled data in 1952 patients across multiple tumour types who received 200 mg tislelizumab every 3 weeks. 0%). 1%). 0% of patients experienced adverse reactions leading to death. 05%).

7% were exposed for longer than 12 months. The safety of tislelizumab given in combination with chemotherapy is based on data in 1950 patients across multiple tumour types who received 200 mg tislelizumab every 3 weeks, with the exception of study BGB A317-315 where patients also received tislelizumab at a dose of 400 mg once every 6 weeks as adjuvant treatment after neoadjuvant therapy and surgery.

3%). 1%). 3% of patients experienced adverse reactions leading to death. 05%). 9% were exposed for 12 months or longer. Tabulated list of adverse reactions Adverse reactions reported in the pooled dataset for patients treated with Tevimbra monotherapy (N= 1952) and in combination with chemotherapy (N = 1950) 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 Tevimbra as monotherapy (N = 1952) and in combination with chemotherapy (N = 1950) Tislelizumab monotherapy N = 1952 Tislelizumab plus chemotherapy N = 1950 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 Very common* Very common* Neutropenia4 Common Very common Lymphopenia5 Common Very common Haemophagocytic lymphohistiocytosis Not known Rare Immune system disorders Sjögren’s syndrome # Uncommon Endocrine disorders Hypothyroidism6 Very common Very common Hyperthyroidism7 Common Common Thyroiditis8 Common Uncommon Adrenal insufficiency9 Uncommon Uncommon Hypophysitis10 Uncommon Uncommon 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 Rare Rare Encephalitis15 # Rare Myasthenia gravis # Rare Eye disorders Uveitis16 Uncommon Uncommon Cardiac disorders Myocarditis17 Uncommon Common* Pericarditis Uncommon Rare Vascular disorders Hypertension18 Common Common Respiratory, thoracic and mediastinal disorders Cough Very common Very common Dyspnoea Common* Common* Pneumonitis19 Common* Common* Gastrointestinal disorders Nausea Very common Very common Diarrhoea20 Very common Very common Stomatitis21 Common Common Pancreatitis22 Uncommon Common Colitis23 Uncommon Common Coeliac disease Rare # Hepatobiliary disorders Hepatitis24 Common* Common* Skin and subcutaneous tissue disorders Rash25 Very common Very common Pruritus Very common Very common Vitiligo26 Uncommon Uncommon Erythema multiforme Uncommon Rare Stevens-Johnson syndrome Rare # Toxic epidermal necrolysis27 Not known* Not known* Musculoskeletal and connective tissue disorders Arthralgia Common Very common Myalgia Common Common Myositis28 Uncommon Uncommon* Arthritis29 Uncommon Common Renal and urinary disorders Nephritis30 Uncommon Uncommon Cystitis noninfective31 Rare # General disorders and administration site conditions Fatigue32 Very common Very common Pyrexia33 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 increased34 Very common Very common Blood alkaline phosphatase increased Common Common Blood creatinine increased Common Very common Injury, poisoning and procedural complications Infusion-related reaction35 Common Common 1 Pneumonia includes preferred terms (PTs) of pneumonia, lower respiratory tract infection, lower respiratory tract infection bacterial, pneumonia bacterial, pneumonia fungal, pneumocystis jirovecii […]

4. 5 to 3 x ULN Withhold2,3 Hepatitis ALT or AST >8 x ULN or total bilirubin >3 x ULN Permanently discontinue3 Grade 3 Withhold2,3 Rash Grade 4 Permanently discontinue3 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).

Severe cutaneous adverse reactions (SCARs) Confirmed SCARs, including SJS or TEN Permanently discontinue Grade 2 or 3 Withold2,3 Colitis Recurrent Grade 3; Grade 4 Permanently discontinue3 Grade 2 or 3 Withhold2,3 Myositis/rhabdomyolysis 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 Tevimbra may be considered after corticosteroid taper. Otherwise, treatment should be discontinued.

Grade 2 Consider withholding treatment until controlled by HRT. Adrenal insufficiency 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 Tevimbra may be considered after corticosteroid taper.

3 Grade 2 Consider withholding treatment until controlled by HRT. Hypophysitis 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 Tevimbra 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 Tevimbra may be considered once metabolic control is achieved. Otherwise, treatment should be discontinued.

5 to 3 x ULN) Withhold2,3 Nephritis with renal dysfunction 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 Grade 2 Withhold2,3 Neurological toxicities Grade 3 or 4 Permanently discontinue3 Grade 3 pancreatitis or Grade 3 or 4 serum amylase or lipase levels increased (>2 x ULN) Withhold2,3 Pancreatitis Grade 4 Permanently discontinue3 Grade 3 Withhold2,3 Other immune-related adverse reactions Recurrent Grade 3; Grade 4 Permanently discontinue3 Other adverse drug reactions Grade 1 Consider pre-medication for prophylaxis of subsequent infusion reactions.

1.