Tevimbra

HOS-100279 · has-adverse-reaction-information · PDF-Seite 11

Summary of the safety profile 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. The most common adverse reactions (≥ 20%) were anaemia (27.7%), aspartate aminotransferase increased (24.7%), fatigue (24.6%), and alanine aminotransferase increased (22.0%). The most common Grade 3/4 adverse reactions (≥ 2%) were anaemia (4.8%), aspartate aminotransferase increased (3.7%), pneumonia (3.6%), hyponatraemia (2.9%), blood bilirubin increased (2.8%), hypertension (2.4%), and fatigue (2.1%). 1.0% of patients experienced adverse reactions leading to death. The adverse reactions leading to death were pneumonia (0.61%), pneumonitis (0.10%), hepatitis (0.10%), thrombocytopenia (0.05%), dyspnoea (0.05%) and decreased appetite (0.05%). Among the 1952 patients, 40.7% were exposed to tislelizumab for longer than 6 months, and 24.7% 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. The most common adverse 11 reactions (≥ 20%) were neutropenia (71.6%), anaemia (67.2%), thrombocytopenia (48.7%), nausea (43.3%), fatigue (40.8%), decreased appetite (40.1%), alanine aminotransferase increased (30.6%), aspartate aminotransferase increased (30.3%), rash (21.4%) and diarrhoea (20.3%). The most common Grade 3/4 adverse reactions (≥ 2%) were neutropenia (45.2%), anaemia (14.5%), thrombocytopenia (14.1%), hyponatraemia (4.6%), hypokalaemia (4.5%), fatigue (4.2%), pneumonia (4.0%), lymphopenia (3.1%), rash (2.9%), decreased appetite (2.6%), aspartate aminotransferase increased (2.2%), alanine aminotransferase increased (2.1%). 1.3% of patients experienced adverse reactions leading to death. The adverse reactions leading to death were pneumonia (0.50%), pneumonitis (0.30%), dyspnoea (0.20%), myocarditis (0.20%), hepatitis (0.05%), thrombocytopenia (0.05%), colitis (0.05%), hypokalaemia (0.05%), and myositis (0.05%). Among the 1950 patients, 56.5% were exposed to tislelizumab for 6 months or longer, and 31.9% were exposed for 12 months or longer. Tabulated list of adverse reactions

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HOS-100275 · has-contraindication-information · PDF-Seite 7

Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.

HOS-100274 · has-indication-information · PDF-Seite 2

Non-small cell lung cancer (NSCLC) Tevimbra, in combination with platinum-containing chemotherapy as neoadjuvant treatment and then continued as monotherapy as adjuvant treatment, is indicated for the treatment of adult patients with resectable NSCLC at high risk of recurrence (for selection criteria, see section 5.1). Tevimbra, in combination with pemetrexed and platinum-containing chemotherapy, is indicated for the first-line treatment of adult patients with non-squamous NSCLC whose tumours have PD-L1 expression on ≥50% of tumour cells with no EGFR or ALK positive mutations and who have: • locally advanced NSCLC and are not candidates for surgical resection or platinum-based chemoradiation, or • metastatic NSCLC. 2 Tevimbra, in combination with carboplatin and either paclitaxel or nab-paclitaxel, is indicated for the first-line treatment of adult patients with squamous NSCLC who have: • locally advanced NSCLC and are not candidates for surgical resection or platinum-based chemoradiation, or • metastatic NSCLC. Tevimbra as monotherapy is indicated for the treatment of adult patients with locally advanced or metastatic NSCLC after prior platinum-based therapy. Patients with EGFR mutant or ALK positive NSCLC should also have received targeted therapies before receiving tislelizumab. Small Cell Lung Cancer (SCLC) Tevimbra, in combination with etoposide and platinum chemotherapy, is indicated for the first-line treatment of adult patients with extensive-stage SCLC. Gastric or gastroesophageal junction (G/GEJ) adenocarcinoma Tevimbra, in combination with platinum and fluoropyrimidine-based chemotherapy, is indicated for the first-line treatment of adult patients with HER-2-negative locally advanced unresectable or metastatic gastric or gastroesophageal junction (G/GEJ) adenocarcinoma whose tumours express PD-L1 with a tumour area positivity (TAP) score ≥ 5% (see section 5.1). Oesophageal squamous cell carcinoma (OSCC) Tevimbra, in combination with platinum-based chemotherapy, is indicated for the first-line treatment of adult patients with unresectable, locally advanced or metastatic OSCC whose tumours express PD-L1 with a TAP score ≥ 5% (see section 5.1). Tevimbra as monotherapy is indicated for the treatment of adult patients with unresectable, locally advanced or metastatic OSCC after prior platinum-based chemotherapy. Nasopharyngeal carcinoma (NPC) Tev

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HOS-100277 · has-interaction-information · PDF-Seite 10

Tislelizumab is a humanised monoclonal antibody, cleared from the circulation through catabolism. As such, formal pharmacokinetic interaction studies have not been conducted. As monoclonal antibodies are not metabolised by cytochrome P450 (CYP) enzymes or other drug-metabolising enzymes, inhibition or induction of these enzymes by co-administered medicinal products is not anticipated to affect the pharmacokinetics of tislelizumab. The use of systemic corticosteroids and other immunosuppressants at baseline, before starting tislelizumab, except for low doses of systemic corticosteroid (10 mg/day prednisone or equivalent), should be avoided because of their potential interference with the pharmacodynamic activity and efficacy of tislelizumab. However, systemic corticosteroids and other immunosuppressants can be used after starting tislelizumab to treat immune-related adverse reactions (see section 4.4). Corticosteroids can also be used as pre-medication when tislelizumab is used in combination with chemotherapy, as antiemetic prophylaxis and/or to alleviate chemotherapy-related adverse reactions.

HOS-100278 · has-pregnancy-information · PDF-Seite 10

Women of childbearing potential/Contraception Tislelizumab should not be used in women of childbearing potential not using effective contraception unless the clinical condition of the woman requires treatment with tislelizumab. Women of childbearing potential should use effective contraception (methods that result in less than 1% pregnancy rates) during treatment and for at least 4 months following the last dose of tislelizumab. 10 Pregnancy There are no available data on the use of tislelizumab in pregnant women. Based on its mechanism of action, tislelizumab can cause foetal harm when administered to a pregnant woman. Animal reproduction studies have not been conducted with tislelizumab. However, in murine models of pregnancy, blockade of PD-1/PD-L1 signalling has been shown to disrupt tolerance to the foetus and to result in increased foetal loss. Human IgG4 (immunoglobulins) are known to cross the placental barrier. Therefore, tislelizumab, being an IgG4 variant, has the potential to be transmitted from the mother to the developing foetus. Women should be advised of the potential risk to a foetus. Tislelizumab should not be used during pregnancy unless the clinical condition of the woman requires treatment with tislelizumab. Breast-feeding It is unknown whether tislelizumab is excreted in human milk. Its effects on breast-fed newborns/infants and on milk production are also unknown. Because of the potential for serious adverse drug reactions in breast-fed newborns/infants from Tevimbra, women should be advised not to breast-feed during treatment and for at least 4 months after the last dose of Tevimbra. Fertility No clinical data are available on the possible effects of tislelizumab on fertility. No reproductive and development toxicity studies have been conducted with tislelizumab. Based on a 3-month repeat-dose toxicity study, there were no notable effects in the male and female reproductive organs in cynomolgus monkeys when tislelizumab was given at doses of 3, 10 or 30 mg/kg every 2 weeks for 13 weeks (7 dose administrations) (see section 5.3).

HOS-100276 · has-warning-information · PDF-Seite 7

Traceability In order to improve the traceability of biological medicinal products, the name and the batch number of the administered product should be clearly recorded. Assessment of PD-L1 status When assessing the PD-L1 status of the tumour, it is important that a well validated methodology is chosen to minimise false negative or false positive determinations. Patient Card Patients treated with Tevimbra must be given the Patient Card to be informed about the risks of immune-related adverse reactions during Tevimbra therapy (see also Package Leaflet). The prescriber must discuss the risks of immune-related adverse reactions during Tevimbra therapy with the patient. Immune-related adverse reactions Immune-related adverse reactions have been reported, including fatal cases, during treatment with tislelizumab (see section 4.8). The majority of these events improved with interruption of tislelizumab, administration of corticosteroids and/or supportive care. Immune-related adverse reactions have also been reported after the last dose of tislelizumab. Immune-related adverse reactions affecting more than one body system can occur simultaneously. For suspected immune-related adverse reactions, adequate evaluation to confirm aetiology or exclude alternative aetiologies, including infection, should be ensured. Based on the severity of the adverse reaction, tislelizumab should be withheld and corticosteroids administered (see section 4.2). Based on limited data from clinical studies, administration of other systemic immunosuppressants can be considered in patients whose immune-related adverse reactions are not controlled with corticosteroid use (see sections 4.2 and 4.8). Upon improvement to Grade ≤1, corticosteroid taper should be initiated and continued over at least 1 month. In patients with pre-existing autoimmune disease (AID), data from observational studies suggest that the risk of immune-mediated adverse reactions following immune-checkpoint inhibitor therapy may be increased as compared with the risk in patients without pre-existing AID. In addition, flares of the underlying AID were frequent, but the majority were mild and manageable. Immune-related pneumonitis Immune-related pneumonitis, including fatal cases, has been reported in patients receiving tislelizumab. Patients should be monitored for signs and symptoms of pneumonitis. Patients with suspected pneumonitis should be evaluated with radiographic imaging and infectious or disease- related

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