Imjudo

Each mL of concentrate for solution for infusion contains 20 mg of tremelimumab.
One vial of 1.25 mL of concentrate contains 25 mg of tremelimumab.
One vial of 15 mL of concentrate contains 300 mg of tremelimumab.
Tremelimumab is a human anti-cytotoxic T-lymphocyte antigen 4 (CTLA-4) immunoglobulin G2 IgG2a monoclonal antibody produced in murine myeloma cells by recombinant DNA technology.
Concentrate for solution for infusion (sterile concentrate) (IV).
Clear to slightly opalescent, colourless to slightly yellow solution, free from or practically free from visible particles. The solution has a pH of approximately 5.5 and an osmolality of approximately 285 mOsm/kg.
Excipients/Inactive Ingredients: Histidine, Histidine hydrochloride monohydrate, Trehalose dihydrate, Disodium edetate dihydrate, Polysorbate 80, Water for injections.

Pharmacotherapeutic group: Other monoclonal antibodies and antibody drug conjugates. ATC code: L01FX20.
Pharmacology: Pharmacodynamics: Mechanism of action: Cytotoxic T lymphocyte-associated antigen (CTLA-4) is primarily expressed on the surface of T lymphocytes. Interaction of CTLA-4 with its ligands, CD80 and CD86, limits effector T-cell activation, through a number of potential mechanisms, but primarily by limiting co-stimulatory signaling through CD28.
Tremelimumab is a selective, fully human IgG2 antibody that blocks CTLA-4 interaction with CD80 and CD86, thus enhancing T-cell activation and proliferation, resulting in increased T-cell diversity and enhanced anti-tumour activity.
The combination of tremelimumab, a CTLA-4 inhibitor and durvalumab, a PD-L1 inhibitor results in improved anti-tumour responses in metastatic non-small cell lung cancer and hepatocellular carcinoma.
Clinical efficacy: HCC - HIMALAYA Study: The efficacy of Tremelimumab (IMJUDO) 300 mg as a single dose in combination with durvalumab was evaluated in the HIMALAYA Study, a randomised, open-label, multicentre study in patients with confirmed uHCC who did not receive prior systemic treatment for HCC. The study included patients with Barcelona Clinic Liver Cancer (BCLC) Stage C or B (not eligible for locoregional therapy) and Child-Pugh Score Class A.
The study excluded patients with brain metastases or a history of brain metastases, co-infection of viral hepatitis B and hepatitis C; active or prior documented gastro-intestinal (GI) bleeding within 12 months; ascites requiring non-pharmacologic intervention within 6 months; hepatic encephalopathy within 12 months before the start of treatment; active or prior documented autoimmune or inflammatory disorders.
Patients with esophageal varices were included except those with active or prior documented GI bleeding within 12 months prior to study entry.
Randomisation was stratified by macrovascular invasion (MVI) (yes vs. no), aetiology of liver disease (confirmed hepatitis B virus vs. confirmed hepatitis C virus vs. others) and ECOG performance status (0 vs. 1). The HIMALAYA study randomised 1171 patients 1:1:1 to receive: Durvalumab 1500 mg every 4 weeks; Tremelimumab (IMJUDO) 300 mg as a single dose + durvalumab 1500 mg; followed by durvalumab 1500 mg every 4 weeks; Sorafenib 400 mg twice daily.
Tumour assessments were conducted every 8 weeks for the first 12 months and then every 12 weeks thereafter. Survival assessments were conducted every month for the first 3 months following treatment discontinuation and then every 2 months.
The primary endpoint was Overall Survival (OS) for the comparison of Tremelimumab (IMJUDO) 300 mg as a single dose in combination with durvalumab vs. sorafenib. Secondary endpoints included Progression-Free Survival (PFS), Investigator-assessed Objective Response Rate (ORR) and Duration of Response (DoR) according to RECIST v1.1.
The demographics and baseline disease characteristics were well balanced between study arms. The baseline demographics of the overall study population were as follows: male (83.7%), age <65 years (50.4%), White (44.6%), Asian (50.7%), Black or African American (1.7%), Other race (2.3%), ECOG PS 0 (62.6%); Child-Pugh Class score A (99.5%), macrovascular invasion (25.2%), extrahepatic spread (53.4%), baseline AFP <400 ng/mL (63.7%), baseline AFP ≥400 ng/mL (34.5%), viral aetiology; hepatitis B (30.6%), hepatitis C (27.2%), uninfected (42.2%), evaluable PD-L1 data (86.3%), PD-L1 Tumour area positivity (TAP) ≥1% (38.9%), PD-L1 TAP <1% (48.3%) [Ventana PD-L1 (SP263) assay].
Results are presented in Table 1 and Figure 1. (See Table 1 and Figure 1.)

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NSCLC - POSEIDON study: POSEIDON was a study designed to evaluate the efficacy of durvalumab with or without Tremelimumab (IMJUDO) in combination with platinum-based chemotherapy. POSEIDON was a randomised, open-label, multicentre study in 1013 metastatic NSCLC patients with no sensitising epidermal growth factor receptor (EGFR) mutation or anaplastic lymphoma kinase (ALK) genomic tumour aberrations. Patients with histologically or cytologically documented metastatic NSCLC were eligible for enrolment. Patients had no prior chemotherapy or any other systemic therapy for metastatic NSCLC. Prior to randomisation, patients had tumour PD-L1 status confirmed by using the Ventana PD-L1 (SP263) assay. Patients had a World Health Organization (WHO)/Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 at enrolment.
The study excluded patients with active or prior documented autoimmune disease; active and/or untreated brain metastases; a history of immunodeficiency; administration of systemic immunosuppression within 14 days before the start of Tremelimumab (IMJUDO) or durvalumab, except physiological dose of systemic corticosteroids; active tuberculosis or hepatitis B or C or HIV infection; or patients receiving live attenuated vaccine within 30 days before or after the start of Tremelimumab (IMJUDO) and/or durvalumab (see Precautions).
Randomisation was stratified by tumour cells (TC) PD-L1 expression (TC ≥50% vs. TC <50%), disease stage (Stage IVA vs. Stage IVB, per the 8th edition of American Joint Committee on Cancer), and histology (non-squamous vs. squamous).
Patients were randomised 1:1:1 to receive: Arm 1: Tremelimumab (IMJUDO) 75 mg with durvalumab 1500 mg and platinum-based chemotherapy every 3 weeks for 4 cycles, followed by durvalumab 1500 mg every 4 weeks as monotherapy. A fifth dose of Tremelimumab (IMJUDO) 75 mg was given at Week 16 alongside durvalumab dose 6.
Arm 2: Durvalumab 1500 mg and platinum-based chemotherapy every 3 weeks for 4 cycles, followed by durvalumab 1500 mg every 4 weeks as monotherapy.
Arm 3: Platinum-based chemotherapy every 3 weeks for 4 cycles. Patients could receive 2 additional cycles (a total of 6 cycles post-randomisation), as clinically indicated, at investigator's discretion.
Patients received one of the following platinum-based chemotherapy regimens: Non-squamous NSCLC: Pemetrexed 500 mg/m² with carboplatin AUC 5-6 or cisplatin 75 mg/m² every 3 weeks. Unless contraindicated by the investigator, pemetrexed maintenance could be given.
Squamous NSCLC: Gemcitabine 1000 or 1250 mg/m² on Days 1 and 8 with cisplatin 75 mg/m² or carboplatin AUC 5-6 on Day 1 every 3 weeks.
Non-squamous or squamous NSCLC: Nab-paclitaxel 100 mg/m² on Days 1, 8, and 15 with carboplatin AUC 5-6 on Day 1 every 3 weeks.
Tremelimumab (IMJUDO) was given up to a maximum of 5 doses unless there was disease progression or unacceptable toxicity. Durvalumab and histology-based pemetrexed maintenance therapy (when applicable) was continued until disease progression or unacceptable toxicity.
Tumour assessments were conducted at Week 6 and Week 12 from the date of randomisation, and then every 8 weeks until confirmed objective disease progression. Survival assessments were conducted every 2 months following treatment discontinuation.
The dual primary endpoints of the study were progression-free survival (PFS) and overall survival (OS) for durvalumab + platinum-based chemotherapy (Arm 2) vs. platinum-based chemotherapy alone (Arm 3). The key secondary endpoints of the study were PFS and OS for Tremelimumab (IMJUDO) + durvalumab + platinum-based chemotherapy (Arm 1) and platinum-based chemotherapy alone (Arm 3). The secondary endpoints included objective response rate (ORR) and duration of response (DoR). PFS, ORR, and DoR were assessed using Blinded Independent Central Review (BICR) according to RECIST v1.1.
The demographics and baseline disease characteristics were well-balanced between study arms. Baseline demographics of the overall study population were as follows: male (76.0%), age ≥65 years (47.1%), age ≥75 years (11.3%) median age 64 years (range: 27 to 87 years), White (55.9%), Asian (34.6%), Black or African American (2.0%), other (7.6%), non-Hispanic or Latino (84.2%), current smoker or past-smoker (78.0%), WHO/ECOG PS 0 (33.4%) and WHO/ECOG PS 1 (66.5%). Disease characteristics were as follows: Stage IVA (50.0%), Stage IVB (49.6%), histological sub-groups of squamous (36.9%), non-squamous (62.9%), brain metastases (10.5%), PD-L1 expression TC ≥50% (28.8%) and PD-L1 expression TC <50% (71.1%).
The study showed a statistically significant improvement in OS with Tremelimumab (IMJUDO) + durvalumab + platinum-based chemotherapy (Arm 1) vs. platinum-based chemotherapy alone (Arm 3). Tremelimumab (IMJUDO) + durvalumab + platinum-based chemotherapy showed a statistically significant improvement in PFS vs. platinum-based chemotherapy alone. The results are summarised as follows. (See Table 2 and Figures 2 and 3.)

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Figure 4 summarises efficacy results of OS by tumour PD-L1 expression in prespecified subgroup analyses. (See Figure 4.)

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Elderly population: A total of 75 patients aged ≥75 years were enrolled in the Tremelimumab (IMJUDO) in combination with durvalumab and platinum-based chemotherapy (n=35) and platinum-based chemotherapy only (n=40) arms of the POSEIDON study. An exploratory HR of 1.05 (95% CI: 0.64, 1.71) for OS was observed for Tremelimumab (IMJUDO) in combination with durvalumab and platinum-based chemotherapy vs. platinum-based chemotherapy within this study subgroup. Due to the exploratory nature of this subgroup analysis no definitive conclusions can be drawn, but caution is suggested when considering this regimen for elderly patients.
Paediatric population: The European Medicines Agency has deferred the obligation to submit the results of studies with tremelimumab in all subsets of the paediatric population in the treatment of malignant neoplasms (except central nervous system tumours, haematopoietic and lymphoid tissue neoplasms). See Dosage & Administration for information on paediatric use.
Pharmacokinetics: The pharmacokinetics (PK) of tremelimumab was assessed for tremelimumab as monotherapy, in combination with durvalumab and in combination with platinum-based chemotherapy.
The PK of tremelimumab was studied in patients with doses ranging from 75 mg to 750 mg or 10 mg/kg administered intravenously once every 4 or 12 weeks as monotherapy, or at a single dose of 300 mg. PK exposure increased dose proportionally (linear PK) at doses ≥75 mg. Steady state was achieved at approximately 12 weeks. Based on population PK analysis that included patients (n=1605) who received tremelimumab monotherapy or in combination with other medicinal products in the dose range of ≥75 mg (or 1 mg/kg) every 3 or 4 weeks, the estimated tremelimumab clearance (CL) and volume of distribution (Vd) were 0.309 l/day and 6.33 l, respectively. The terminal half-life was approximately 14.2 days. The primary elimination pathways of tremelimumab are protein catabolism via reticuloendothelial system or target mediated disposition.
Special populations: Age (18-87 years), body weight (34-149 kg), gender, positive anti-drug antibody (ADA) status, albumin levels, LDH levels, creatinine levels, tumour type, race or ECOG/WHO status had no clinically significant effect on the PK of tremelimumab.
Renal impairment: Mild (creatinine clearance (CrCL) 60 to 89 mL/min) and moderate renal impairment (creatinine clearance (CrCL) 30 to 59 mL/min) had no clinically significant effect on the PK of tremelimumab. The effect of severe renal impairment (CrCL 15 to 29 mL/min) on the PK of tremelimumab is unknown; the potential need for dose adjustment cannot be determined. However, as IgG monoclonal antibodies are not primarily cleared via renal pathways, a change in renal function is not expected to influence tremelimumab exposure.
Hepatic impairment: Mild hepatic impairment (bilirubin ≤ ULN and AST > ULN or bilirubin >1.0 to 1.5 x ULN and any AST) and moderate hepatic impairment (bilirubin >1.5 to 3 x ULN and any AST) had no clinically significant effect on the PK of tremelimumab. The effect of severe hepatic impairment (bilirubin >3.0 x ULN and any AST) on the PK of tremelimumab is unknown; the potential need for dose adjustment cannot be determined. However, as IgG monoclonal antibodies are not primarily cleared via hepatic pathways, a change in hepatic function is not expected to influence tremelimumab exposure.
Toxicology: Preclinical safety data: Animal toxicology: In the chronic 6-month study in cynomolgus monkeys, treatment with tremelimumab was associated with dose-related incidence in persistent diarrhoea and skin rash, scabs and open sores, which were dose-limiting. These clinical signs were also associated with decreased appetite and body weight and swollen peripheral lymph nodes. Histopathological findings correlating with the observed clinical signs included reversible chronic inflammation in the cecum and colon, mononuclear cell infiltration in the skin and hyperplasia in lymphoid tissues.
A dose-dependent increase in the incidence and severity of mononuclear cell infiltration with or without mononuclear cell inflammation was observed in the salivary gland, pancreas (acinar), thyroid, parathyroid, adrenal, heart, esophagus, tongue, periportal liver area, skeletal muscle, prostate, uterus, pituitary, eye (conjunctiva, extra ocular muscles), and choroid plexus of the brain. No NOAEL was found in this study with animals treated with the lowest dose of 5 mg/kg/week, however the intermediate dose of 15 mg/kg week was considered the highest non-severely toxic dose (HNSTD). This dose provided an exposure-based safety margin of 1.77-5.33 to clinical relevant exposure based on the clinical dosing regimen of either a 300 mg single dose or 75 mg every three weeks.
Carcinogenicity and mutagenicity: The carcinogenic and genotoxic potential of tremelimumab has not been evaluated.
Reproductive toxicology: Mononuclear cell infiltration in prostate and uterus was observed in repeat dose toxicity studies. Since animal fertility studies have not been conducted with tremelimumab, the relevance of these findings for fertility is unknown. In reproduction studies, administration of tremelimumab to pregnant cynomolgus monkeys during the period of organogenesis was not associated with maternal toxicity or effects on pregnancy losses, foetal weights, or external, visceral, skeletal abnormalities or weights of selected foetal organs.

Tremelimumab (IMJUDO) in combination with durvalumab is indicated for the first line treatment of adults with advanced or unresectable hepatocellular carcinoma (HCC).
Tremelimumab (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.

Treatment must be initiated and supervised by a physician experienced in the treatment of cancer.
Posology: The recommended dose of Tremelimumab (IMJUDO) is presented in Table 3. Tremelimumab (IMJUDO) is administered as an intravenous infusion over 1 hour. (See Table 3.)

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Dose escalation or reduction is not recommended during treatment with Tremelimumab (IMJUDO) in combination with durvalumab. Treatment withholding or discontinuation may be required based on individual safety and tolerability.
Guidelines for management of immune-mediated adverse reactions are described in Table 4 (see Precautions). Refer also to the SmPC for durvalumab. (See Table 4.)

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For suspected immune-mediated adverse reactions, adequate evaluation should be performed to confirm aetiology or exclude alternate aetiologies.
Special populations: Paediatric population: The safety and efficacy of Tremelimumab (IMJUDO) in children and adolescents below 18 years of age have not been established. No data are available.
Elderly: No dose adjustment is required for elderly patients (≥65 years of age) (see Pharmacology: Pharmacokinetics under Actions). Data on patients aged 75 years or older with metastatic NSCLC are limited (see Precautions).
Renal impairment: No dose adjustment of Tremelimumab (IMJUDO) is recommended in patients with mild or moderate renal impairment. Data from patients with severe renal impairment are too limited to draw conclusions on this population (see Pharmacology: Pharmacokinetics under Actions).
Hepatic impairment: No dose adjustment of Tremelimumab (IMJUDO) is recommended for patients with mild or moderate hepatic impairment. Tremelimumab (IMJUDO) has not been studied in patients with severe hepatic impairment (see Pharmacology: Pharmacokinetics under Actions).
Method of administration: Tremelimumab (IMJUDO) is for intravenous use, it is administered as an intravenous infusion after dilution, over 1 hour (see Special precautions for disposal and other handling under Cautions for Usage).
For instructions on dilution of the medicinal product before administration, see Special precautions for disposal and other handling under Cautions for Usage.
Tremelimumab (IMJUDO) in combination with durvalumab: When Tremelimumab (IMJUDO) is given in combination with durvalumab, administer Tremelimumab (IMJUDO) as a separate intravenous infusion prior to durvalumab on the same day. Refer to the SmPC for durvalumab administration information.
Tremelimumab (IMJUDO) in combination with durvalumab and platinum-based chemotherapy: When Tremelimumab (IMJUDO) is given in combination with durvalumab and platinum-based chemotherapy, Tremelimumab (IMJUDO) is given first, followed by durvalumab and then platinum-based chemotherapy on the day of dosing.
When Tremelimumab (IMJUDO) is given as a fifth dose in combination with durvalumab and pemetrexed maintenance therapy at week 16, Tremelimumab (IMJUDO) is given first, followed by durvalumab and then pemetrexed maintenance therapy on the day of dosing.
Tremelimumab (IMJUDO), durvalumab, and platinum-based chemotherapy are administered as separate intravenous infusions. Tremelimumab (IMJUDO) and durvalumab are each given over 1 hour. For platinum-based chemotherapy, refer to the SmPC for administration information. For pemetrexed maintenance therapy, refer to the SmPC for administration information. Separate infusion bags and filters for each infusion should be used.
During cycle 1, Tremelimumab (IMJUDO) is to be followed by durvalumab starting approximately 1 hour (maximum 2 hours) after the end of the Tremelimumab (IMJUDO) infusion. Platinum-based chemotherapy infusion should start approximately 1 hour (maximum 2 hours) after the end of the durvalumab infusion. If there are no clinically significant concerns during cycle 1, then at the physician's discretion, subsequent cycles of durvalumab can be given immediately after Tremelimumab (IMJUDO) and the time period between the end of the durvalumab infusion and the start of chemotherapy can be reduced to 30 minutes.

There is no information on overdose with tremelimumab. In case of overdose, patients should be closely monitored for signs or symptoms of adverse reactions, and appropriate symptomatic treatment instituted immediately.

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

Traceability: 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 Adverse Reactions). 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 Dosage & Administration.
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 Adverse Reactions). 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 Dosage & Administration.
Immune-mediated colitis: Immune-mediated colitis or diarrhoea, 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 Adverse Reactions). Intestinal perforation and large intestine perforation were reported in patients receiving tremelimumab in combination with durvalumab. Patients should be monitored for signs and symptoms of colitis/diarrhoea and intestinal perforation and managed as recommended in Dosage & Administration.
Immune-mediated endocrinopathies: Immune-mediated hypothyroidism, hyperthyroidism and thyroiditis: Immune-mediated hypothyroidism, hyperthyroidism and thyroiditis occurred in patients receiving tremelimumab in combination with durvalumab, or with durvalumab and chemotherapy, and hypothyroidism may follow hyperthyroidism (see Adverse Reactions). Patients should be monitored for abnormal thyroid function tests prior to and periodically during treatment and as indicated based on clinical evaluation. Immune-mediated hypothyroidism, hyperthyroidism, and thyroiditis should be managed as recommended in Dosage & Administration.
Immune-mediated adrenal insufficiency: Immune-mediated adrenal insufficiency occurred in patients receiving tremelimumab in combination with durvalumab, or with durvalumab and chemotherapy (see Adverse Reactions). Patients should be monitored for clinical signs and symptoms of adrenal insufficiency. For symptomatic adrenal insufficiency, patients should be managed as recommended in Dosage & Administration.
Immune-mediated type 1 diabetes mellitus: Immune-mediated type 1 diabetes mellitus, which can first present as diabetic ketoacidosis that can be fatal if not detected early, occurred in patients receiving tremelimumab in combination with durvalumab, or with durvalumab and chemotherapy (see Adverse Reactions). Patients should be monitored for clinical signs and symptoms of type 1 diabetes mellitus. For symptomatic type 1 diabetes mellitus, patients should be managed as recommended in Dosage & Administration.
Immune-mediated hypophysitis/hypopituitarism: Immune-mediated hypophysitis or hypopituitarism occurred in patients receiving tremelimumab in combination with durvalumab, or with durvalumab and chemotherapy (see Adverse Reactions). Patients should be monitored for clinical signs and symptoms of hypophysitis or hypopituitarism. For symptomatic hypophysitis or hypopituitarism, patients should be managed as recommended in Dosage & Administration.
Immune-mediated nephritis: Immune-mediated nephritis, 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 Adverse Reactions). Patients should be monitored for abnormal renal function tests prior to and periodically during treatment and managed as recommended in Dosage & Administration.
Immune-mediated rash: Immune-mediated rash or dermatitis (including pemphigoid), 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 Adverse Reactions). Events of Stevens-Johnson Syndrome or toxic epidermal necrolysis have been reported in patients treated with PD-1 and CTLA-4 inhibitors. Patients should be monitored for signs and symptoms of rash or dermatitis and managed as recommended in Dosage & Administration.
Immune-mediated myocarditis: Immune-mediated myocarditis, which can be fatal, occurred in patients receiving tremelimumab in combination with durvalumab, or with durvalumab and chemotherapy (see Adverse Reactions). Patients should be monitored for signs and symptoms of immune-mediated myocarditis and managed as recommended in Dosage & Administration.
Immune-mediated pancreatitis: Immune-mediated pancreatitis, occurred in patients receiving tremelimumab in combination with durvalumab and chemotherapy (see Adverse Reactions). Patients should be monitored for signs and symptoms of immune-mediated pancreatitis and managed as recommended in Dosage & Administration.
Other immune-mediated adverse reactions: Given the mechanism of action of tremelimumab in combination with durvalumab, other potential immune-mediated adverse reactions may occur. The following immune-related adverse reactions have been observed in patients treated with tremelimumab in combination with durvalumab, or with durvalumab and chemotherapy: myasthenia gravis, myositis, polymyositis, meningitis, encephalitis, Guillain-Barré syndrome, immune thrombocytopenia, cystitis noninfective and pancreatitis (see Adverse Reactions). Patients should be monitored for signs and symptoms and managed as recommended in Dosage & Administration.
Infusion-related reactions: Patients should be monitored for signs and symptoms of infusion-related reactions. Severe infusion-related reactions have been reported in patients receiving tremelimumab in combination with durvalumab (see Adverse Reactions). Infusion-related reactions should be managed as recommended in Dosage & Administration.
Disease-specific precaution: Metastatic NSCLC: Limited data are available in elderly patients (≥75 years) treated with tremelimumab in combination with durvalumab and platinum-based chemotherapy (see Adverse Reactions and Pharmacology: Pharmacodynamics under Actions). Careful consideration of the potential benefit/risk of this regimen on an individual basis is recommended.
Patients excluded from clinical studies: Advanced or unresectable HCC: Patients with the following were excluded from clinical studies: Child-Pugh Score B or C, main portal vein thrombosis, liver transplant, uncontrolled hypertension, history of, or current brain metastases, spinal cord compression, co-infection of viral hepatitis B and hepatitis C, active or prior documented gastrointestinal (GI) bleeding within 12 months, ascites requiring non-pharmacologic intervention within 6 months, hepatic encephalopathy within 12 months before the start of treatment, active or prior documented autoimmune or inflammatory disorders. In the absence of data, tremelimumab should be used with caution in these populations after careful consideration of the potential benefit/risk on an individual basis.
Metastatic NSCLC: Patients with the following were excluded from clinical studies: active or prior documented autoimmune disease; active and/or untreated brain metastases; a history of immunodeficiency; administration of systemic immunosuppression within 14 days before the start of tremelimumab or durvalumab, except physiological dose of systemic corticosteroids (<10 mg/day prednisone or equivalent); uncontrolled intercurrent illness; active tuberculosis or hepatitis B or C or HIV infection or patients receiving live attenuated vaccine within 30 days before or after the start of tremelimumab or durvalumab. In the absence of data, tremelimumab should be used with caution in these populations after careful consideration of the potential benefit/risk on an individual basis.
Sodium content: This medicinal product contains less than 1 mmol sodium (23 mg) per dose, that is to say essentially 'sodium-free'.
Effects on ability to drive and use machines: Tremelimumab has no or negligible influence on the ability to drive and use machines.

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 Pharmacology: Toxicology: Preclinical safety data under Actions.) Tremelimumab (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 Tremelimumab (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 Pharmacology: Toxicology: Preclinical safety data under Actions). The clinical relevance of these findings for fertility is unknown.

Summary of the safety profile: Tremelimumab (IMJUDO) in combination with durvalumab: 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 Tables 5a and 5b.)
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%).
Tremelimumab (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 adverse reactions leading to treatment discontinuation were pneumonia (1.2%) and colitis (0.9%).
Tremelimumab was interrupted due to adverse reactions in 40.6% of patients. The most common adverse reactions leading to dose interruption were neutropenia (13.6%), thrombocytopenia (5.8%), leukopenia (4.5%), diarrhoea (3.0%), pneumonia (2.7%), aspartate aminotransferase increased/alanine aminotransferase increased (2.4%), fatigue (2.4%), lipase increased (2.4%), colitis (2.1%), hepatitis (2.1%) and rash (2.1%).
Tabulated list of adverse reactions: Tables 5a and 5b, unless otherwise stated, lists the incidence of adverse reactions (ADRs) in patients treated with tremelimumab 300 mg in combination with durvalumab in the HCC pool of 462 patients, and Tremelimumab (IMJUDO) in combination with durvalumab and platinum-based chemotherapy in the POSEIDON Study, in which 330 patients received tremelimumab. In the POSEIDON study, patients were exposed to tremelimumab during a median of 20 weeks.
Adverse reactions are listed according to system organ class in MedDRA. Within each system organ class, the ADRs are presented in decreasing frequency. The corresponding frequency category for each ADR 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 <1/1000); very rare (<1/10,000); not known (cannot be estimated from available data). Within each frequency grouping, ADRs are presented in order of decreasing seriousness. (See Tables 5a and 5b.)

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Description of selected adverse reactions: Tremelimumab is associated with immune-mediated adverse reactions. Most of these, including severe reactions, resolved following initiation of appropriate medical therapy or withdrawal of tremelimumab. The data for the following immune-mediated adverse reactions are based on 2280 patients from nine studies across multiple tumour types who received tremelimumab 75 mg every 4 weeks or 1 mg/kg every 4 weeks in combination with durvalumab 1500 mg every 4 weeks, 20 mg/kg every 4 weeks or 10 mg/kg every 2 weeks. This combined safety dataset excludes the POSEIDON Study (and patients treated with tremelimumab in combination with durvalumab and platinum-based chemotherapy). Details for the significant adverse reactions for tremelimumab when given in combination with durvalumab and platinum-based chemotherapy are presented if clinically relevant differences were noted in comparison to tremelimumab in combination with durvalumab.
The data as follows also reflects information for significant adverse reactions for tremelimumab 300 mg in combination with durvalumab in the HCC pool (n=462).
The management guidelines for these adverse reactions are described in Precautions.
Immune-mediated pneumonitis: In the combined safety database with tremelimumab in combination with durvalumab (n=2280), immune-mediated pneumonitis occurred in 86 (3.8%) patients, including Grade 3 in 30 (1.3%) patients, Grade 4 in 1 (<0.1%) patient, and Grade 5 (fatal) in 7 (0.3%) patients. The median time to onset was 57 days (range: 8-912 days). All patients received systemic corticosteroids and 79 of the 86 patients received high-dose corticosteroid treatment (at least 40 mg prednisone or equivalent per day). Seven patients also received other immunosuppressants. Treatment was discontinued in 39 patients. Resolution occurred in 51 patients.
In the HCC pool (n=462), immune-mediated pneumonitis occurred in 6 (1.3%) patients, including Grade 3 in 1 (0.2%) patient and Grade 5 (fatal) in 1 (0.2%) patient. The median time to onset was 29 days (range: 5-774 days). All patients received systemic corticosteroids, and 5 of the 6 patients received high-dose corticosteroid treatment (at least 40 mg prednisone or equivalent per day). One patient also received other immunosuppressants. Treatment was discontinued in 2 patients. Resolution occurred in 3 patients.
Immune-mediated hepatitis: In the combined safety database with tremelimumab in combination with durvalumab (n=2280), immune-mediated hepatitis occurred in 80 (3.5%) patients, including Grade 3 in 48 (2.1%) patients, Grade 4 in 8 (0.4%) patients and Grade 5 (fatal) in 2 (<0.1%) patients. The median time to onset was 36 days (range: 1-533 days). All patients received systemic corticosteroids and 68 of the 80 patients received high-dose corticosteroid treatment (at least 40 mg prednisone or equivalent per day). Eight patients also received other immunosuppressants. Treatment was discontinued in 27 patients. Resolution occurred in 47 patients.
In the HCC pool (n=462), immune-mediated hepatitis occurred in 34 (7.4%) patients, including Grade 3 in 20 (4.3%) patients, Grade 4 in 1 (0.2%) patient and Grade 5 (fatal) in 3 (0.6%) patients. The median time to onset was 29 days (range: 13-313 days). All patients received systemic corticosteroids, and 32 of the 34 patients received high-dose corticosteroid treatment (at least 40 mg prednisone or equivalent per day). Nine patients also received other immunosuppressants. Treatment was discontinued in 10 patients. Resolution occurred in 13 patients.
Immune-mediated colitis: In the combined safety database with tremelimumab in combination with durvalumab (n=2280), immune-mediated colitis or diarrhoea occurred in 167 (7.3%) patients, including Grade 3 in 76 (3.3%) patients and Grade 4 in 3 (0.1%) patients. The median time to onset was 57 days (range: 3-906 days). All patients received systemic corticosteroids and 151 of the 167 patients received high-dose corticosteroid treatment (at least 40 mg prednisone or equivalent per day). Twenty-two patients also received other immunosuppressants. Treatment was discontinued in 54 patients. Resolution occurred in 141 patients.
In the HCC pool (n=462), immune-mediated colitis or diarrhoea occurred in 31 (6.7%) patients, including Grade 3 in 17 (3.7%) patients. The median time to onset was 23 days (range: 2-479 days). All patients received systemic corticosteroids, and 28 of the 31 patients received high-dose corticosteroid treatment (at least 40 mg prednisone or equivalent per day). Four patients also received other immunosuppressants. Treatment was discontinued in 5 patients. Resolution occurred in 29 patients.
Intestinal perforation was observed in patients receiving tremelimumab in combination with durvalumab (rare) in studies outside of the HCC pool.
Immune-mediated endocrinopathies: Immune-mediated hypothyroidism: In the combined safety database with tremelimumab in combination with durvalumab (n=2280), immune-mediated hypothyroidism occurred in 209 (9.2%) patients, including Grade 3 in 6 (0.3%) patients. The median time to onset was 85 days (range: 1-624 days). Thirteen patients received systemic corticosteroids and 8 of the 13 received high-dose corticosteroid treatment (at least 40 mg prednisone or equivalent per day). Treatment discontinued in 3 patients. Resolution occurred in 52 patients. Immune-mediated hypothyroidism was preceded by immune-mediated hyperthyroidism in 25 patients or immune-mediated thyroiditis in 2 patients.
In the HCC pool (n=462), immune-mediated hypothyroidism occurred in 46 (10.0%) patients. The median time to onset was 85 days (range: 26-763 days). One patient received high-dose corticosteroid treatment (at least 40 mg prednisone or equivalent per day). All patients required other therapy including hormone replacement therapy. Resolution occurred in 6 patients. Immune-mediated hypothyroidism was preceded by immune-mediated hyperthyroidism in 4 patients.
Immune-mediated hyperthyroidism: In the combined safety database with tremelimumab in combination with durvalumab (n=2280), immune-mediated hyperthyroidism occurred in 62 (2.7%) patients, including Grade 3 in 5 (0.2%) patients. The median time to onset was 33 days (range: 4-176 days). Eighteen patients received systemic corticosteroids, and 11 of the 18 patients received high-dose corticosteroid treatment (at least 40 mg prednisone or equivalent per day). Fifty-three patients required other therapy (thiamazole, carbimazole, propylthiouracil, perchlorate, calcium channel blocker or beta-blocker). One patient discontinued treatment due to hyperthyroidism. Resolution occurred in 47 patients.
In the HCC pool (n=462), immune-mediated hyperthyroidism occurred in 21 (4.5%) patients, including Grade 3 in 1 (0.2%) patient. The median time to onset was 30 days (range: 13-60 days). Four patients received systemic corticosteroids, and all of the four patients received high-dose corticosteroid treatment (at least 40 mg prednisone or equivalent per day). Twenty patients required other therapy (thiamazole, carbimazole, propylthiouracil, perchlorate, calcium channel blocker, or beta-blocker). One patient discontinued treatment due to hyperthyroidism. Resolution occurred in 17 patients.
Immune-mediated thyroiditis: In the combined safety database with tremelimumab in combination with durvalumab (n=2280), immune-mediated thyroiditis occurred in 15 (0.7%) patients, including Grade 3 in 1 (<0.1%) patient. The median time to onset was 57 days (range: 22-141 days). Five patients received systemic corticosteroids and 2 of the 5 patients received high-dose corticosteroid treatment (at least 40 mg prednisone or equivalent per day). Thirteen patients required other therapy including, hormone replacement therapy, thiamazole, carbimazole, propylthiouracil, perchlorate, calcium channel blocker, or beta-blocker. No patients discontinued treatment due to immune-mediated thyroiditis. Resolution occurred in 5 patients.
In the HCC pool (n=462), immune-mediated thyroiditis occurred in 6 (1.3%) patients. The median time to onset was 56 days (range: 7-84 days). Two patients received systemic corticosteroids, and 1 of the 2 patients received high-dose corticosteroid treatment (at least 40 mg prednisone or equivalent per day). All patients required other therapy including hormone replacement therapy. Resolution occurred in 2 patients.
Immune-mediated adrenal insufficiency: In the combined safety database with tremelimumab in combination with durvalumab (n=2280), immune-mediated adrenal insufficiency occurred in 33 (1.4%) patients, including Grade 3 in 16 (0.7%) patients and Grade 4 in 1 (<0.1%) patient. The median time to onset was 105 days (range: 20-428 days). Thirty-two patients received systemic corticosteroids, and 10 of the 32 patients received high-dose corticosteroid treatment (at least 40 mg prednisone or equivalent per day). Treatment was discontinued in one patient. Resolution occurred in 11 patients.
In the HCC pool (n=462), immune-mediated adrenal insufficiency occurred in 6 (1.3%) patients, including Grade 3 in 1 (0.2%) patient. The median time to onset was 64 days (range: 43-504 days). All patients received systemic corticosteroids, and 1 of the 6 patients received high-dose corticosteroid treatment (at least 40 mg prednisone or equivalent per day). Resolution occurred in 2 patients.
Immune-mediated type 1 diabetes mellitus: In the combined safety database with tremelimumab in combination with durvalumab (n=2280), immune-mediated type 1 diabetes mellitus occurred in 6 (0.3%) patients, including Grade 3 in 1 (<0.1%) patient and Grade 4 in 2 (<0.1%) patients. The median time to onset was 58 days (range: 7-220 days). All patients required insulin. Treatment was discontinued for 1 patient. Resolution occurred in 1 patient.
Immune-mediated type 1 diabetes mellitus was observed in patients receiving tremelimumab in combination with durvalumab (uncommon) in studies outside of the HCC pool.
Immune-mediated hypophysitis/hypopituitarism: In the combined safety database with tremelimumab in combination with durvalumab (n=2280), immune-mediated hypophysitis/hypopituitarism occurred in 16 (0.7%) patients, including Grade 3 in 8 (0.4%) patients. The median time to onset for the events was 123 days (range: 63-388 days). All patients received systemic corticosteroids and 8 of the 16 patients received high-dose corticosteroid treatment (at least 40 mg prednisone or equivalent per day). Four patients also required endocrine therapy. Treatment was discontinued in 2 patients. Resolution occurred in 7 patients.
In the HCC pool (n=462), immune-mediated hypophysitis/hypopituitarism occurred in 5 (1.1%) patients. The median time to onset for the events was 149 days (range: 27-242 days). Four patients received systemic corticosteroids, and 1 of the 4 patients received high-dose corticosteroid treatment (at least 40 mg prednisone or equivalent per day). Three patients also required endocrine therapy. Resolution occurred in 2 patients.
Immune-mediated nephritis: In the combined safety database with tremelimumab in combination with durvalumab (n=2280), immune-mediated nephritis occurred in 9 (0.4%) patients, including Grade 3 in 1 (<0.1%) patient. The median time to onset was 79 days (range: 39-183 days). All patients received systemic corticosteroids and 7 patients received high-dose corticosteroid treatment (at least 40 mg prednisone or equivalent per day). Treatment was discontinued in 3 patients. Resolution occurred in 5 patients.
In the HCC pool (n=462), immune-mediated nephritis occurred in 4 (0.9%) patients, including Grade 3 in 2 (0.4%) patients. The median time to onset was 53 days (range: 26-242 days). All patients received systemic corticosteroids, and 3 of the 4 patients received high-dose corticosteroid treatment (at least 40 mg prednisone or equivalent per day). Treatment was discontinued in 2 patients. Resolution occurred in 3 patients.
Immune-mediated rash: In the combined safety database with tremelimumab in combination with durvalumab (n=2280), immune-mediated rash or dermatitis (including pemphigoid) occurred in 112 (4.9%) patients, including Grade 3 in 17 (0.7%) patients. The median time to onset was 35 days (range: 1-778 days). All patients received systemic corticosteroids, and 57 of the 112 patients received high-dose corticosteroid treatment (at least 40 mg prednisone or equivalent per day). Treatment was discontinued in 10 patients. Resolution occurred in 65 patients.
In the HCC pool (n=462), immune-mediated rash or dermatitis (including pemphigoid) occurred in 26 (5.6%) patients, including Grade 3 in 9 (1.9%) patients and Grade 4 in 1 (0.2%) patient. The median time to onset was 25 days (range: 2-933 days). All patients received systemic corticosteroids and 14 of the 26 patients received high-dose corticosteroid treatment (at least 40 mg prednisone or equivalent per day). One patient received other immunosuppressants. Treatment was discontinued in 3 patients. Resolution occurred in 19 patients.
Infusion-related reactions: In the combined safety database with tremelimumab in combination with durvalumab (n=2280), infusion-related reactions occurred in 45 (2.0%) patients, including Grade 3 in 2 (<0.1%) patients. There were no Grade 4 or 5 events.
Laboratory abnormalities: In patients treated with tremelimumab in combination with durvalumab and platinum-based chemotherapy in the POSEIDON study (n=330), the proportion of patients who experienced a shift from baseline to a Grade 3 or 4 laboratory abnormality was as follows: 6.2% for alanine aminotransferase increased, 5.2% for aspartate aminotransferase increased, 4.0% for blood creatinine increased, 9.4% for amylase increased and 13.6% for lipase increased. The proportion of patients who experienced a TSH shift from baseline that was ≤ ULN to > ULN was 24.8% and a TSH shift from baseline that was ≥ LLN to < LLN was 32.9%.
Immunogenicity: As with all therapeutic proteins, there is a potential for immunogenicity. Immunogenicity of tremelimumab is based on pooled data in 2075 patients who were treated with tremelimumab 75 mg or 1 mg/kg and evaluable for the presence of anti-drug antibodies (ADAs). Two-hundred fifty-two patients (12.1%) tested positive for treatment-emergent ADAs. Neutralising antibodies against tremelimumab were detected in 10.0% (208/2075) patients. The presence of ADAs did not impact tremelimumab pharmacokinetics, and there was no apparent effect safety.
In the HIMALAYA study, of the 182 patients who were treated with tremelimumab 300 mg as a single dose in combination with durvalumab and evaluable for the presence of ADAs against tremelimumab, 20 (11.0%) patients tested positive for treatment-emergent ADAs. Neutralising antibodies against tremelimumab were detected in 4.4% (8/182) patients. The presence of ADAs did not have an apparent effect on pharmacokinetics or safety.
In the POSEIDON study, of the 278 patients who were treated with tremelimumab 75 mg in combination with durvalumab 1500 mg every 3 weeks and platinum-based chemotherapy and evaluable for the presence of ADAs, 38 (13.7%) patients tested positive for treatment-emergent ADAs. Neutralising antibodies against tremelimumab were detected in 11.2% (31/278) of patients. The presence of ADAs did not have an apparent effect on pharmacokinetics or safety.
Elderly: Data from HCC patients 75 years of age or older are limited.
In the POSEIDON study in patients treated with tremelimumab in combination with durvalumab and platinum-based chemotherapy, some differences in safety were reported between elderly (≥65 years) and younger patients. The safety data from patients 75 years of age or older are limited to a total of 74 patients. There was a higher frequency of serious adverse reactions and discontinuation of any study treatment due to adverse reactions in 35 patients aged 75 years of age or older treated with tremelimumab in combination with durvalumab and platinum-based chemotherapy (45.7% and 28.6%, respectively) relative to 39 patients aged 75 years of age or older who received platinum-based chemotherapy only (35.9% and 20.5%, respectively).
Reporting of suspected adverse reactions: Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions.

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 Precautions).
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.

Incompatibilities: In the absence of compatibility studies, this medicinal product must not be mixed with other medicinal products.
Special precautions for disposal and other handling: Preparation of solution: Tremelimumab (IMJUDO) is supplied as a single-dose vial and does not contain any preservatives, aseptic technique must be observed.
Visually inspect medicinal product for particulate matter and discolouration. Tremelimumab (IMJUDO) is clear to slightly opalescent, colourless to slightly yellow solution. Discard the vial if the solution is cloudy, discoloured or visible particles are observed. Do not shake the vial.
Withdraw the required volume from the vial(s) of Tremelimumab (IMJUDO) and transfer into an intravenous bag containing sodium chloride 9 mg/mL (0.9%) solution for injection, or glucose 50 mg/mL (5%) solution for injection. Mix diluted solution by gentle inversion. The final concentration of the diluted solution should be between 0.1 mg/mL and 10 mg/mL. Do not freeze or shake the solution.
Care must be taken to ensure the sterility of the prepared solution.
Do not re-enter the vial after withdrawal of the medicinal product.
Discard any unused portion left in the vial.
Administration: Administer the infusion solution intravenously over 60 minutes through an intravenous line containing a sterile, low-protein binding 0.2 or 0.22 micron in-line filter.
Do not co-administer other medicinal products through the same infusion line.
Disposal: Any unused medicinal product or waste material should be disposed of in accordance with local requirements.

Shelf life: Unopened vial: Refer to the outer carton.
Diluted solution: Chemical and physical in-use stability has been demonstrated for up to 28 days at 2°C to 8°C and for up to 48 hours at room temperature (up to 25°C) from the time of preparation.
From a microbiological point of view, the prepared solution for infusion should be used immediately. If not used immediately, in-use storage times and conditions prior to use are the responsibility of the user and would normally not be longer than 24 hours at 2°C to 8°C or 12 hours at room temperature (up to 25°C), unless dilution has taken place in controlled and validated aseptic conditions.
Lack of microbial growth in the prepared solution for infusion has been demonstrated for up to 28 days at 2°C to 8°C and for up to 48 hours at room temperature (up to 25°C) from the time of preparation.
Special precautions for storage: Store at temperatures between 2-8°C in a refrigerator.
Do not freeze.
Store in the original package in order to protect from light.
For storage conditions after dilution of the medicinal product, see Shelf life as previously mentioned.

Targeted Cancer Therapy / Cancer Immunotherapy

L01FX20 - tremelimumab ; Belongs to the class of other monoclonal antibodies and antibody drug conjugates. Used in the treatment of cancer.

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