Tremelimumab

J01 - Antibacterials for systemic use Antibody approved 2022 Parenteral

JFDA label: Imjudo 300mg/15ml Concentrate for Solution for IV Infusion

Mechanism of Action

Inhibitor of Cytotoxic T-lymphocyte protein 4 — Cytotoxic T-lymphocyte protein 4 inhibitor

Target	Action	Gene / class
Cytotoxic T-lymphocyte protein 4 efficacy	INHIBITOR	CTLA4 · Surface antigen

Indications

Approved

Carcinoma, Hepatocellular — hepatocellular carcinoma
Carcinoma, Non-Small-Cell Lung — non-small cell lung carcinoma
Neoplasms — neoplasm

Off-label

Adenocarcinoma, Follicular
Bile Duct Neoplasms
Biliary Tract Neoplasms
Breast Neoplasms
Carcinoma, Pancreatic Ductal
Carcinoma, Renal Cell
Carcinoma, Squamous Cell
Cholangiocarcinoma
Colorectal Neoplasms
Dysgerminoma
Fallopian Tube Neoplasms
Genital Neoplasms, Female
Glioblastoma
HIV Infections
Head and Neck Neoplasms
Lung Neoplasms
Melanoma
Mesothelioma
Neoplasms, Germ Cell and Embryonal
Neuroendocrine Tumors
Ovarian Neoplasms
Pancreatic Neoplasms
Prostatic Neoplasms
Prostatic Neoplasms, Castration-Resistant
Sarcoma
Seminoma
Small Cell Lung Carcinoma
Squamous Cell Carcinoma of Head and Neck
Stomach Neoplasms
Thyroid Neoplasms
Urinary Bladder Neoplasms
Uveal Melanoma

Contraindications

Source: openFDA

None. None. ( 4 ) Absolute

Adverse Reactions

Very Common >10%Common 1–10%Uncommon 0.1–1% Rare 0.01–0.1%Very Rare <0.01%Not Known

Cardiac disorders (1)

Uncommon Cardiac Arrest

Vascular disorders (2)

Common Of Patients Included Hemorrhage · Were Hemorrhage

Nervous system disorders (1)

Uncommon Hemorrhage Intracranial

Hepatobiliary disorders (6)

Common And Hepatitis · Ast Increased · Hepatitis · Of Patients Included Alt Increased

Uncommon And Immune-Mediated Hepatitis · Hepatic Failure

Renal and urinary disorders (2)

Common Acute Kidney Injury · And Blood Creatinine Increased

Blood and lymphatic system disorders (7)

Very Common And Thrombocytopenia · Anemia · Laboratory Abnormalities Were Neutropenia · Leukopenia

Common And Anemia · And Febrile Neutropenia · Thrombocytopenia

Endocrine disorders (1)

Common Hyperthyroidism

Metabolism and nutrition disorders (1)

Very Common Hyponatremia

Gastrointestinal disorders (4)

Very Common Adverse Reactions Were Nausea · Decreased Appetite

Common Diarrhea · Vomiting

Skin and subcutaneous tissue disorders (1)

Common Rash

Infections and infestations (3)

Very Common Of Patients Were Pneumonia

Common Pneumonia · Sepsis

Investigations (2)

Very Common Lipase Increased

Common Amylase Increased

General disorders and administration site conditions (4)

Very Common And Fatigue · Lymphocytopenia

Common Including Death · Pyrexia

Respiratory, thoracic and mediastinal disorders (1)

Uncommon Pneumonitis

Dosing

Source: openFDA

• Administer IMJUDO as an intravenous infusion over 60 minutes after dilution. ( 2.3 ) • uHCC: Weight 30 kg and more: IMJUDO 300 mg as a single dose in combination with durvalumab 1,500 mg at Cycle 1/Day 1, followed by durvalumab as a single agent every 4 weeks ( 2.1 ) Weight less than 30 kg: IMJUDO 4 mg/kg as a single dose in combination with durvalumab 20 mg/kg at Cycle 1/Day 1, followed by durvalumab as a single agent every 4 weeks ( 2.1 ) • Metastatic NSCLC: Weight 30 kg and more: 75 mg every 3 weeks in combination with durvalumab 1,500 mg and platinum-based chemotherapy for 4 cycles, and then administer durvalumab 1,500 mg every 4 weeks as a single agent with histology-based pemetrexed therapy every 4 weeks, and a fifth dose of IMJUDO 75 mg in combination with durvalumab dose 6 at week 16 ( 2.1 ) Weight less than 30 kg: 1 mg/kg every 3 weeks in combination with durvalumab 20 mg/kg and platinum-based chemotherapy for 4 cycles, and then administer durvalumab 20 mg/kg every 4 weeks as a single agent with histology-based pemetrexed therapy every 4 weeks, and a fifth dose of IMJUDO 1 mg/kg in combination with durvalumab dose 6 at week 16 ( 2.1 ) • See full Prescribing Information for preparation and administration instructions and dosage modifications for adverse reactions. 2.1 Recommended Dosage The recommended dosages of IMJUDO are presented in Tables 1, 2 and 3. Administer IMJUDO as an intravenous infusion after dilution as recommended [see Dosage and Administration (2.3) ]. IMJUDO in Combination with Durvalumab Table 1. Recommended dosage of IMJUDO Indication Recommended IMJUDO Dosage Duration of Therapy uHCC Patients with a body weight of 30 kg and more : • A single dose of IMJUDO Administer IMJUDO prior to durvalumab on the same day. 300 mg followed by durvalumab Refer to the Prescribing Information for durvalumab dosing information. 1,500 mg at Day 1 of Cycle 1; • Continue durvalumab 1,500 mg as a single agent every 4 weeks Patients with a body weight of less than 30 kg: • A single dose of IMJUDO 4 mg/kg followed by durvalumab 20 mg/kg at Day 1 of Cycle 1; • Continue durvalumab 20 mg/kg as a single agent every 4 weeks After Cycle 1 of combination therapy, administer durvalumab as a single agent every 4 weeks until disease progression or unacceptable toxicity IMJUDO in Combination with Durvalumab and Platinum-Based Chemotherapy The recommended dosage schedule and regimens for IMJUDO for the treatment of metastatic non-small cell lung cancer (NSCLC) are provided in Tables 2 and 3. Weigh patients prior to each infusion. Calculate the appropriate dose using Table 3 below based on the patient’s weight and tumor histology. Table 2: Recommended Dosage Schedule Week continue durvalumab until disease progression or intolerable toxicity. , dosing interval change from every 3 weeks to every 4 weeks starting at cycle 5. 0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 Cycle: 1 2 3 4 5 6 7 8 IMJUDO intravenous infusion over 60 minutes [see Dosage and Administration (2.3) ]. , if patients receive fewer than 4 cycles of platinum-based chemotherapy, the remaining cycles of IMJUDO (up to a total of 5) should be given after the platinum-based chemotherapy phase, in combination with durvalumab, every 4 weeks. X X X X X Durvalumab , X X X X X X X X Chemotherapy X X X X X optional pemetrexed therapy from week 12 until disease progression or intolerable toxicity for patients with non-squamous disease who received treatment with pemetrexed and carboplatin/cisplatin. X X X Table 3: Recommended Regimen and Dosage Tumor Histology Patient Weight IMJUDO Dosage Durvalumab Refer to the Prescribing Information for dosing information. Dosage Platinum-based Chemotherapy Regimen Non-Squamous ≥ 30 kg 75 mg 1,500 mg • carboplatin & nab-paclitaxel OR • carboplatin or cisplatin & pemetrexed < 30 kg 1 mg/kg 20 mg/kg Squamous ≥ 30 kg 75 mg 1,500 mg • carboplatin & nab-paclitaxel OR • carboplatin or cisplatin & gemcitabine < 30 kg 1 mg/kg 20 mg

Warnings & Precautions

Source: openFDA

Warnings & Precautions

• Immune-Mediated Adverse Reactions ( 5.1 ) Immune-mediated adverse reactions, which may be severe or fatal, can occur in any organ system or tissue, including the following: immune-mediated pneumonitis, immune-mediated colitis, immune-mediated hepatitis, immune-mediated endocrinopathies, immune-mediated nephritis with renal dysfunction, immune-mediated dermatologic adverse reactions and immune-mediated pancreatitis. o Monitor for early identification and management. Evaluate liver enzymes, creatinine, adrenocorticotropic hormone level and thyroid function at baseline and before each dose. o Withhold or permanently discontinue based on severity and type of reaction. • Infusion-Related Reactions: Interrupt, slow the rate of infusion, or permanently discontinue treatment based on the severity of the reaction. ( 5.2 ) • Embryo-Fetal Toxicity: Can cause fetal harm. Advise females of reproductive potential of the potential risk to a fetus and use of effective contraception. ( 5.3 , 8.1 , 8.3 )

Severe and Fatal Immune-Mediated Adverse Reactions IMJUDO is a monoclo

Severe and Fatal Immune-Mediated Adverse Reactions IMJUDO is a monoclonal antibody that blocks T-cell inhibitory signals induced by the CTLA-4 pathway, thereby removing inhibition of the immune response. In combination with durvalumab, a PD-L1 inhibitor, these drugs have the potential for induction of immune-mediated adverse reactions. Immune-mediated adverse reactions listed herein may not be inclusive of all possible severe and fatal immune-mediated reactions. Immune-mediated adverse reactions, which may be severe or fatal, can occur in any organ system or tissue. Immune-mediated adverse reactions can occur at any time after starting IMJUDO in combination with durvalumab. While immune-mediated adverse reactions usually manifest during treatment, immune-mediated adverse reactions can also manifest after discontinuation of IMJUDO and/or durvalumab. Early identification and management of immune-mediated adverse reactions are essential to ensure safe use of IMJUDO in combination with durvalumab. Monitor for signs and symptoms that may be clinical manifestations of underlying immune-mediated adverse reactions. Evaluate clinical chemistries including liver enzymes, creatinine, adrenocorticotropic hormone (ACTH) level, and thyroid function at baseline and before each dose. Institute medical management promptly, including specialty consultation as appropriate. Withhold or permanently discontinue IMJUDO and durvalumab depending on severity [see Dosage and Administration (2.2) ] . In general, if combination of IMJUDO and durvalumab requires interruption or discontinuation, administer systemic corticosteroid therapy (1 to 2 mg/kg/day prednisone or equivalent) until improvement to Grade 1 or less. Upon improvement to Grade 1 or less, initiate corticosteroid taper and continue to taper over at least 1 month. Consider administration of other systemic immunosuppressants in patients whose immune-mediated adverse reactions are not controlled with corticosteroid therapy. Toxicity management guidelines for adverse reactions that do not necessarily require systemic steroids (e.g., endocrinopathies and dermatologic reactions) are discussed below. Immune-Mediated Pneumonitis IMJUDO in combination with durvalumab can cause immune-mediated pneumonitis, which may be fatal. IMJUDO with Durvalumab Immune-mediated pneumonitis occurred in 1.3% (5/388) of patients receiving IMJUDO in combination with durvalumab, including fatal (0.3%) and Grade 3 (0.2%) adverse reactions. Events reso

Infusion-Related Reactions IMJUDO in combination with durvalumab can c

Infusion-Related Reactions IMJUDO in combination with durvalumab can cause severe or life-threatening infusion-related reactions. Monitor for signs and symptoms of infusion-related reactions. Interrupt, slow the rate of, or permanently discontinue IMJUDO and durvalumab based on the severity [see Dosage and Administration (2.2) ] . For Grade 1 or 2 infusion-related reactions, consider using pre-medications with subsequent doses. IMJUDO with Durvalumab Infusion-related reactions occurred in 10 (2.6%) patients receiving IMJUDO in combination with durvalumab. IMJUDO with Durvalumab and Platinum-Based Chemotherapy Infusion-related reactions occurred in 2.9% (17/596) of patients receiving IMJUDO in combination with durvalumab and platinum-based chemotherapy, including Grade 3 (0.3%) adverse reactions.

Embryo-Fetal Toxicity Based on findings from animal studies and its me

Embryo-Fetal Toxicity Based on findings from animal studies and its mechanism of action, IMJUDO can cause fetal harm when administered to a pregnant woman. In animal studies, CTLA-4 blockade is associated with higher incidence of pregnancy loss. Advise pregnant women and females of reproductive potential of the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during treatment with IMJUDO and for 3 months after the last dose of IMJUDO [see Use in Specific Populations (8.1 , 8.3 )].

Pregnancy & Lactation

Lactation

Probably Unsafe Hale L4

No information is available on the clinical use of tremelimumab during breastfeeding.

Registered Products (2)

Brand	Form / strength	Pack	Agent	Citizen (JOD)
Imjudo 25mg/1.25ml Concentrate for Solution for for IV infusion	Infusion Tremelimumab 25 mg/1.25 ml	1 vial	Shawi & Rushedat Drug Store	—
Imjudo 300mg/15ml Concentrate for Solution for IV Infusion	Infusion Tremelimumab 300 mg/15 ml	1 vial	Shawi & Rushedat Drug Store	—