Imjudo · 4.3 Contraindications · 1

HOS-288938 · has-adverse-reaction-information · PDF-Seite 11

Summary of the safety profile IMJUDO in combination with durvalumab 11 The safety of tremelimumab 300 mg as a single dose in combination with durvalumab, is based on pooled data in 462 HCC patients (HCC pool) from the HIMALAYA Study and another study in HCC patients, Study 22. The most common (> 10%) adverse reactions were rash (32.5%), pruritus (25.5%), diarrhoea (25.3%), abdominal pain (19.7%), aspartate aminotransferase increased/alanine aminotransferase increased (18.0%), pyrexia (13.9%), hypothyroidism (13.0%), cough/productive cough (10.8%) and oedema peripheral (10.4%) (see Table 3). The most common (> 3%) severe adverse reactions (NCI CTCAE Grade ≥ 3) were aspartate aminotransferase increased/alanine aminotransferase increased (8.9%), lipase increased (7.1%), amylase increased (4.3%) and diarrhoea (3.9%). The most common (> 2%) serious adverse reactions were colitis (2.6%), diarrhoea (2.4%) and pneumonia (2.2%). The frequency of treatment discontinuation due to adverse reactions is 6.5%. The most common adverse reactions leading to treatment discontinuation were hepatitis (1.5%) and aspartate aminotransferase increased/alanine aminotransferase increased (1.3%). IMJUDO in combination with durvalumab and chemotherapy The safety of tremelimumab given in combination with durvalumab and chemotherapy is based on data in 330 patients with metastatic NSCLC. The most common (> 10%) adverse reactions were anaemia (49.7%), nausea (41.5%), neutropenia (41.2%), fatigue (36.1%), decreased appetite (28.2%), rash (25.8%), thrombocytopenia (24.5%), diarrhoea (21.5%), leukopenia (19.4%), constipation (19.1%), vomiting (18.2%), aspartate aminotransferase increased/alanine aminotransferase increased (17.6%), pyrexia (16.1%), upper respiratory tract infections (15.5%), pneumonia (14.8%), hypothyroidism (13.3%), arthralgia (12.4%), cough/productive cough (12.1%) and pruritus (10.9%). The most common (> 3%) severe adverse reactions (NCI CTCAE Grade ≥ 3) were neutropenia (23.9%), anaemia (20.6%), pneumonia (9.4%), thrombocytopenia (8.2%), leukopenia (5.5%), fatigue (5.2%), lipase increased (3.9%) and amylase increased (3.6%). The most common (> 2%) serious adverse reactions were pneumonia (11.5%), anaemia (5.5%), thrombocytopenia (3%), colitis (2.4%), diarrhoea (2.4%), pyrexia (2.4%) and febrile neutropenia (2.1%). Tremelimumab was discontinued due to adverse reactions in 4.5% of patients. The most common adver

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HOS-288934 · has-contraindication-information · PDF-Seite 7

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

HOS-288933 · has-indication-information · PDF-Seite 2

IMJUDO in combination with durvalumab is indicated for the first line treatment of adults with advanced or unresectable hepatocellular carcinoma (HCC). IMJUDO in combination with durvalumab and platinum-based chemotherapy is indicated for the first- line treatment of adults with metastatic non-small cell lung cancer (NSCLC) with no sensitising EGFR mutations or ALK positive mutations.

HOS-288936 · has-interaction-information · PDF-Seite 11

The use of systemic corticosteroids or immunosuppressants before starting tremelimumab, except physiological dose of systemic corticosteroids (≤ 10 mg/day prednisone or equivalent), is not recommended because of their potential interference with the pharmacodynamic activity and efficacy of tremelimumab. However, systemic corticosteroids or other immunosuppressants can be used after starting tremelimumab to treat immune-related adverse reactions (see section 4.4). No formal pharmacokinetic (PK) drug-drug interaction studies have been conducted with tremelimumab. Since the primary elimination pathways of tremelimumab are protein catabolism via reticuloendothelial system or target-mediated disposition, no metabolic drug-drug interactions are expected. PK drug-drug interactions between tremelimumab in combination with durvalumab and platinum-based chemotherapy were assessed in the POSEIDON study and showed no clinically meaningful PK interactions between tremelimumab, durvalumab, nab-paclitaxel, gemcitabine, pemetrexed, carboplatin or cisplatin in the concomitant treatment.

HOS-288937 · has-pregnancy-information · PDF-Seite 11

Women of childbearing potential/Contraception Women of childbearing potential should use effective contraception during treatment with tremelimumab and for at least 3 months after the last dose of tremelimumab. Pregnancy There are no data on the use of tremelimumab in pregnant women. Based on its mechanism of action, and placental transfer of human IgG2, tremelimumab has the potential to impact maintenance of pregnancy and may cause foetal harm when administered to a pregnant woman. Animal studies do not indicate direct or indirect harmful effects with respect to reproductive toxicity (see section 5.3). IMJUDO is not recommended during pregnancy and in women of childbearing potential not using effective contraception during treatment and for at least 3 months after the last dose. Breast-feeding There is no information regarding the presence of tremelimumab in human milk, the absorption and effects on the breast-fed infant, or the effects on milk production. Human IgG2 is known to be excreted in human milk. A risk to the breastfed child cannot be excluded. Breast-feeding should be discontinued during treatment with IMJUDO and for at least 3 months after the last dose. Fertility There are no data on the potential effects of tremelimumab on fertility in humans or animals. However, mononuclear cell infiltration in prostate and uterus was observed in repeat-dose toxicity studies (see Section 5.3). The clinical relevance of these findings for fertility is unknown.

HOS-288935 · has-warning-information · PDF-Seite 7

Refer to section 4.2, Table 2 for recommended treatment modifications. For suspected immune- mediated adverse reactions, adequate evaluation should be performed to confirm aetiology or exclude alternate aetiologies. Based on the severity of the adverse reaction, IMJUDO in combination with durvalumab should be withheld and corticosteroids administered. Upon improvement to ≤ Grade 1, corticosteroid taper should be initiated and continued over at least 1 month. Consider increasing dose of corticosteroids and/or using additional systemic immunosuppressants if there is worsening or no improvement. Traceability 7 In order to improve the traceability of biological medicinal products, the tradename and the batch number of the administered product should be clearly recorded. Immune-mediated pneumonitis Immune-mediated pneumonitis or interstitial lung disease, defined as requiring use of systemic corticosteroids and with no clear alternate aetiology, occurred in patients receiving tremelimumab in combination with durvalumab, or with durvalumab and chemotherapy (see section 4.8). Patients should be monitored for signs and symptoms of pneumonitis. Suspected pneumonitis should be confirmed with radiographic imaging and other infectious and disease-related aetiologies excluded, and managed as recommended in section 4.2. For Grade 2 events, an initial dose of 1-2 mg/kg/day prednisone or equivalent should be initiated followed by a taper. For Grade 3 or 4 events, an initial dose of 2-4 mg/kg/day methylprednisolone or equivalent should be initiated followed by a taper. Immune-mediated hepatitis Immune-mediated hepatitis, defined as requiring use of systemic corticosteroids and with no clear alternate aetiology, occurred in patients receiving tremelimumab in combination with durvalumab, or with durvalumab and chemotherapy (see section 4.8). Monitor alanine aminotransferase, aspartate aminotransferase, total bilirubin, and alkaline phosphatase levels prior to initiation of treatment and prior to each subsequent infusion. Additional monitoring is to be considered based on clinical evaluation. Immune-mediated hepatitis should be managed as recommended in section 4.2. Corticosteroids should be administered with an initial dose of 1-2 mg/kg/day prednisone or equivalent followed by taper for all grades. Immune-mediated colitis Immune-mediated colitis or diarrhoea, defined as requiring use of systemic corticosteroids and

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