Imjudo

Tremelimumab.

Each mL contains 20 mg of tremelimumab.
Each vial of 15 mL contains 300 mg of tremelimumab.
IMJUDO 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; 20 mg/mL in a single-dose vial for intravenous administration.
Sterile, preservative-free, clear to slightly opalescent, colourless to slightly yellow solution, free from or practically free from visible particles.
Excipients/Inactive Ingredients: L-histidine, L-histidine hydrochloride monohydrate, α,α-Trehalose dihydrate, Disodium edetate dihydrate, Polysorbate 80, Water for Injection.

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 signalling 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 antitumour immune activity.
The combination of durvalumab, a PD-L1 inhibitor, and tremelimumab functions to enhance anti-tumour T-cell activation and function at multiple stages of the immune response, enhancing anti-tumour immunity.
The effect of STRIDE on the quantities of proliferative cytotoxic CD8+ T cells was evaluated in Study 22 in patients with uHCC using a CD8+Ki67+ assay. At Day 15 a marked increase of proliferating CD8+ T cell populations was observed in the STRIDE arm compared to the durvalumab monotherapy arm. Patients receiving STRIDE also experienced a higher Objective Response Rate (ORR) compared to other treatment arms and responders across all arms exhibited higher median proliferative cytotoxic CD8+ T cell when compared to non-responding patients.
Clinical efficacy and safety: HCC - HIMALAYA Study: The efficacy of STRIDE was evaluated in the HIMALAYA study, a randomised, open-label, multicenter study in patients with confirmed uHCC who did not receive prior systemic treatment for HCC. The study included patients with 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 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), etiology of liver disease (confirmed hepatitis B virus vs. confirmed hepatitis C virus vs. others) and ECOG performance status (0 vs. 1).
The HIMALAYA study randomized 1171 patients 1:1:1 to receive: D: durvalumab 1500 mg every 4 weeks; STRIDE: IMJUDO 300 mg as a single priming dose + durvalumab 1500 mg; followed by durvalumab 1500 mg every 4 weeks; S: 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 OS. Key secondary endpoints were PFS, Investigator assessed ORR and DoR according to RECIST v1.1. Patient-Reported Outcomes (PROs) were also assessed.
The demographics and baseline disease characteristics were generally representative for patients with uHCC. 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 (2.3%), ECOG PS 0 (62.6%); Child-Pugh Class score A (99.5%), macrovascular invasion (25.2%), extrahepatic spread (53.4%), viral etiology; hepatitis B (30.6%), hepatitis C (27.2%), uninfected (42.2%), 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].
The study demonstrated a statistically significant and clinically meaningful improvement in OS with STRIDE vs. S [HR=0.78 [95% CI 0.66, 0.92]; p=0.0035]. See Table 1 and figure.

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Pharmacokinetics: The pharmacokinetics (PK) of tremelimumab was assessed for IMJUDO in combination with durvalumab.
The pharmacokinetics of tremelimumab was studied in patients with solid tumours at a single priming dose of 300 mg.
There was no clinically meaningful difference between the PK of tremelimumab as monotherapy or in combination with durvalumab.
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, mild renal impairment (creatinine clearance (CRCL) 60 to 89 mL/min), moderate renal impairment (creatinine clearance (CRCL) 30 to 59 mL/min), mild hepatic impairment (bilirubin ≤ ULN and AST > ULN or bilirubin > 1.0 to 1.5 × ULN and any AST), moderate hepatic impairment (bilirubin > 1.5 to 3 x ULN and any AST) or ECOG/WHO status had no clinically significant effect on the PK of tremelimumab.
The effect of severe renal impairment (CRCL 15 to 29 mL/min) or severe hepatic impairment (bilirubin > 3.0 x ULN and any AST) on the PK of tremelimumab is unknown.
Elderly: No dose adjustment is required for elderly patients (≥ 65 years of age). Of the 462 patients with uHCC treated with STRIDE, 173 (37.4%) patients were 65 years or older and 63 (13.6%) patients were 75 years or older. No overall clinically meaningful differences in safety or efficacy were reported between patients ≥ 65 years of age and younger patients.
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 IMJUDO 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. Neutralizing 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 on efficacy and safety.
In the HIMALAYA study, of the 182 patients who were treated with STRIDE and evaluable for the presence of ADAs against tremelimumab, 20 (11.0%) patients tested positive for treatment-emergent ADAs. Neutralizing 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.
Immunogenicity assay results are highly dependent on several factors, including assay sensitivity and specificity, assay methodology, sample handling, timing of sample collection, concomitant medications and underlying disease.
For these reasons, comparison of incidence of antibodies to tremelimumab with the incidence of antibodies to other products may be misleading.
Toxicology: Preclinical safety data: Carcinogenicity and mutagenicity: The carcinogenic and genotoxic potential of tremelimumab has not been evaluated.
Reproductive toxicology: Animal fertility studies have not been conducted with tremelimumab. 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 at exposure levels approximately 4 to 31-times higher than those observed at a recommended dose range of 75 mg to 300 mg based on area under the curve (AUC).
Animal toxicology and/or pharmacology: In the chronic six-month toxicity study in cynomolgus monkeys, weekly intravenous administration of 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, and mononuclear cell infiltration in a wide variety of tissues including the skin and lymphoid tissues, with dose-related incidence and severity.
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 observed adverse effect level (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 to clinical relevant exposure.

Hepatocellular Carcinoma (HCC): IMJUDO in combination with durvalumab is indicated for the treatment of patients with unresectable hepatocellular carcinoma (uHCC) who have not received prior systemic therapy.

The recommended dose of IMJUDO is presented in Table 2.
IMJUDO is administered as an intravenous infusion over 1 hour. (See Table 2.)

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Dose reduction or escalation is not recommended during treatment with IMJUDO in combination with durvalumab. Treatment withholding or discontinuation may be required based on individual safety and tolerability.
Immune-mediated adverse reactions requiring specific treatment modification and management are summarized in Table 3. Refer to Precautions for further monitoring and evaluation information. (See Table 3.)

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For suspected immune-mediated adverse reactions, adequate evaluation should be performed to confirm etiology or exclude alternate etiologies.
For non-immune-mediated adverse reactions, withhold IMJUDO and/or durvalumab for Grade 2 and 3 adverse reactions until ≤ Grade 1 or return to baseline. IMJUDO and durvalumab should be discontinued for Grade 4 adverse reactions (with the exception of Grade 4 laboratory abnormalities, about which the decision to discontinue should be based on accompanying clinical signs/symptoms and clinical judgment).
Special patient populations: Based on a population pharmacokinetic analysis, no dose adjustment of IMJUDO is recommended based on patient age, body weight, gender and race (see Pharmacology: Pharmacokinetics under Actions).
Paediatric and adolescents: The safety and effectiveness of IMJUDO have not been established in children and adolescents aged less than 18 years.
Elderly (≥ 65 years): No dose adjustment is required for elderly patients (≥ 65 years of age) (see Pharmacology: Pharmacodynamics and Pharmacokinetics under Actions).
Renal Impairment: Based on a population pharmacokinetic analysis, no dose adjustment of IMJUDO is recommended in patients with mild to moderate renal impairment. IMJUDO has not been studied in patients with severe renal impairment (see Pharmacology: Pharmacokinetics under Actions).
Hepatic Impairment: Based on a population pharmacokinetic analysis, no dose adjustment of IMJUDO is recommended for patients with mild or moderate hepatic impairment. IMJUDO has not been studied in patients with severe hepatic impairment (see Pharmacology: Pharmacokinetics under Actions).
Method of Administration: For instructions on dilution of the medicinal product before administration, see Instructions for use, handling and disposal under Cautions for Usage.

There is no specific treatment in the event of tremelimumab overdose, and symptoms of overdose are not established. In the event of an overdose, physicians should follow general supportive measures and should treat symptomatically.

Hypersensitivity to the active substance or to any of the excipients.

Refer to Dosage & Administration, Table 3 for recommended treatment modifications and management of immune-mediated adverse reactions.
Immune-mediated pneumonitis: Immune-mediated pneumonitis or interstitial lung disease, defined as requiring use of systemic corticosteroids and with no clear alternate etiology, occurred in patients receiving IMJUDO in combination with durvalumab (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 etiologies 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 etiology, occurred in patients receiving IMJUDO in combination with durvalumab (see Adverse Reactions). Patients should be monitored for abnormal liver prior to initiation of treatment and prior to each subsequent infusion. 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 etiology, occurred in patients receiving IMJUDO in combination with durvalumab (see Adverse Reactions). Cytomegalovirus (CMV) infection/reactivation has been reported in patients with corticosteroid-refractory immune-mediated colitis. In cases of corticosteroid-refractory colitis, consider repeating infectious workup to exclude alternative etiologies. Intestinal perforation and large intestine perforation were reported in patients receiving IMJUDO 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/thyroiditis: Immune-mediated hypothyroidism, hyperthyroidism or thyroiditis have occurred in patients receiving IMJUDO in combination with durvalumab (see Adverse Reactions). Patients should be monitored for abnormal thyroid function tests prior to and periodically during treatment and managed as recommended in Dosage & Administration.
Immune-mediated adrenal insufficiency: Immune-mediated adrenal insufficiency occurred in patients receiving IMJUDO in combination with durvalumab (see Adverse Reactions). Patients should be monitored for clinical signs and symptoms of adrenal insufficiency and managed as recommended in Dosage & Administration.
Immune-mediated type 1 diabetes mellitus: Immune-mediated type 1 diabetes mellitus, which can present with diabetic ketoacidosis that can be fatal if not detected early, occurred in patients receiving IMJUDO in combination with durvalumab (see Adverse Reactions). Patients should be monitored for clinical signs and symptoms of type 1 diabetes mellitus and managed as recommended in Dosage & Administration.
Immune-mediated hypophysitis/hypopituitarism: Immune-mediated hypophysitis or hypopituitarism occurred in patients receiving IMJUDO in combination with durvalumab (see Adverse Reactions). Patients should be monitored for clinical signs and symptoms of hypophysitis or hypopituitarism and managed as recommended in Dosage & Administration.
Immune-mediated nephritis: Immune-mediated nephritis, defined as requiring use of systemic corticosteroids and with no clear alternate etiology, occurred in patients receiving IMJUDO in combination with durvalumab (see Adverse Reactions). Patients should be monitored for abnormal renal function tests prior to and periodically during treatment with IMJUDO in combination with durvalumab 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 etiology, occurred in patients receiving IMJUDO in combination with durvalumab (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 IMJUDO in combination with durvalumab (see Adverse Reactions). Patients should be monitored for signs and symptoms of immune-mediated myocarditis and managed as recommended in Dosage & Administration.
Other immune-mediated adverse reactions: Given the mechanism of action of IMJUDO and durvalumab, other potential immune-mediated adverse reactions may occur in patients receiving the combination of IMJUDO with durvalumab. The following immune-mediated adverse reactions have been observed: myasthenia gravis, myositis, polymyositis, Guillain-Barré syndrome, meningitis, cystitis noninfective, immune thrombocytopenia, pancreatitis, hemophagocytic lymphohistiocytosis, autoimmune hemolytic anemia, aplastic anemia, immune-mediated arthritis, uveitis, and encephalitis (see Adverse Reactions). Iritis, and other ocular inflammatory toxicities can occur. Some cases can be associated with retinal detachment. Various grades of visual impairment to include blindness can occur. If uveitis occurs in combination with other immune-mediated adverse reactions, consider a Vogt-Koyanagi-Harada-like syndrome, as this may require treatment with systemic steroids to reduce the risk of permanent vision loss. 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 and managed as recommended in Dosage & Administration. Severe infusion-related reactions have been reported in patients receiving IMJUDO in combination with durvalumab (see Adverse Reactions).
Effects on ability to drive and use machines: Based on its pharmacodynamic properties, tremelimumab is unlikely to affect the ability to drive and use machines. However, if patients experience adverse reactions affecting their ability to concentrate and react, they should be advised to use caution when driving or operating machinery.

Pregnancy: In animal reproduction studies, administration of tremelimumab to pregnant cynomolgus monkeys during the period of organogenesis was not associated with maternal toxicity or any effects on pregnancy maintenance or embryofoetal development (see Pharmacology: Toxicology: Preclinical safety data under Actions). There are no data on the use of tremelimumab in pregnant women. Based on its mechanism of action, tremelimumab has the potential to impact pregnancy maintenance and may cause foetal harm when administered to a pregnant woman. Human IgG2 is known to cross the placental barrier. Tremelimumab 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 breastfed infant, or the effects on milk production. Human IgG2 is excreted in human milk. Because of the potential for adverse reactions from tremelimumab in breastfed infants, lactating women are advised not to breastfeed during treatment 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.

Overall summary of adverse drug reactions: The safety of STRIDE is based on data in 462 patients from the HIMALAYA study and Study 22 (uHCC, HCC pool).
Tabulated list of adverse reactions: Table 4 lists the incidence of ADRs in patients treated with STRIDE in the HCC pool. Adverse drug reactions are listed according to system organ class in MedDRA. Within each system organ class, the adverse drug reactions are presented in decreasing frequency. Within each frequency grouping, ADRs are presented in order of decreasing seriousness. In addition, the corresponding frequency category for each ADR is based on the CIOMS III convention and 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 determined (cannot be estimated from available data). (See Table 4.)

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Description of selected adverse reactions: The data as follows reflects information for significant adverse reactions for STRIDE in the HCC pool (n=462).
The management guidelines for these adverse reactions are described in Dosage & Adminstration and Precautions.
Immune-mediated pneumonitis: HCC pool: In patients receiving STRIDE, 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: HCC pool: In patients receiving STRIDE, 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: HCC pool: In patients receiving STRIDE, 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 not observed in patients receiving STRIDE but was observed in patients receiving tremelimumab in combination with durvalumab (rare) in studies outside of the HCC pool.
Immune-mediated endocrinopathies: Immune-mediated hypothyroidism: HCC pool: In patients receiving STRIDE, 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 (thiamazole, carbimazole, propylthiouracil, perchlorate, calcium channel blocker, or beta-blocker). Resolution occurred in 6 patients. Immune-mediated hypothyroidism was preceded by immune-mediated hyperthyroidism in 4 patients.
Immune-mediated hyperthyroidism: HCC pool: In patients receiving STRIDE, 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 coticosteriods, 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: HCC pool: In patients receiving STRIDE, 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, thiamazole, carbimazole, propylthiouracil, perchlorate, calcium channel blocker, or beta-blocker. Resolution occurred in 2 patients.
Immune-mediated adrenal insufficiency: HCC pool: In patients receiving STRIDE, 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: HCC pool: In patients receiving STRIDE, immune-mediated type 1 diabetes mellitus was not observed but was observed patients receiving tremelimumab in combination with durvalumab (uncommon) in studies outside of the HCC pool.
Immune-mediated hypophysitis/hypopituitarism: HCC pool: In patients receiving STRIDE, 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: HCC pool: In patients receiving STRIDE, 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 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: HCC pool: In patients receiving STRIDE, 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%) patients. 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: HCC pool: In patients receiving STRIDE, infusion-related reactions occurred in 7 (1.5%) patients.

Tremelimumab is an immunoglobulin and the primary elimination pathways of tremelimumab are protein catabolism via reticuloendothelial system or target-mediated disposition; therefore, no formal pharmacokinetic (PK) drug-drug interaction studies have been conducted with tremelimumab since no metabolic drug-drug interactions are expected. PK drug-drug interaction between tremelimumab in combination with durvalumab was assessed in the HIMALAYA study and no clinically meaningful PK drug-drug interaction was identified.
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.

Incompatibilities: Tremelimumab: No incompatibilities between IMJUDO and 9 g/L (0.9%) sodium chloride or 50 g/L (5%) dextrose in polyvinylchloride or polyolefin intravenous (IV) bags have been observed.
This drug product must not be mixed with other drug products except those mentioned in Instructions for use, handling and disposal.
Do not co-administer other drugs through the same intravenous line.
Instructions for use, handling and disposal: Preparation of solution: IMJUDO is supplied as a single-dose vial and does not contain any preservatives, aseptic technique must be observed.
Visually inspect drug product for particulate matter and discolouration. 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 IMJUDO and transfer into an IV bag containing 0.9% Sodium Chloride Injection, or 5% Dextrose 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 prepared solutions.
Do not re-enter the vial after withdrawal of drug.
Discard any unused portion left in the vial.
Administration: Administer infusion solution intravenously over 1 hour through an intravenous line containing a sterile, low-protein binding 0.2 or 0.22 micron filter.
Do not co-administer other drugs through the same infusion line.
Any unused medicinal product or waste material should be disposed of in accordance with local requirements.

Shelf-life: After preparation of infusion solution: IMJUDO does not contain a preservative. Administer infusion solution immediately once prepared. If infusion solution is not administered immediately and it needs to be stored, follow the below recommendations: 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 30°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 not be longer than 28 days at 2°C to 8°C or 48 hours at room temperature (up to 30°C).
Unopened vial: Store vials under refrigeration at 2°C to 8°C in original carton to protect from light.
Do not freeze.
Do not shake.
Diluted Solution: For storage conditions after preparation of the infusion, see Shelf-life as previously mentioned.

Cancer Immunotherapy

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

POM