IMJUDO (Tremelimumab)

What Is IMJUDO and What Is It Used For?

IMJUDO contains the active substance tremelimumab, a fully human monoclonal antibody designed to target and bind to cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4). CTLA-4 is an inhibitory receptor expressed on T-cells that normally acts as a "brake" on the immune system. When CTLA-4 binds to its ligands (CD80 and CD86) on antigen-presenting cells, it sends an inhibitory signal that dampens T-cell activation and proliferation. By blocking this interaction, tremelimumab releases the brake, allowing T-cells to become more fully activated and mount a more robust immune response against cancer cells.

The concept of immune checkpoint inhibition has revolutionized cancer treatment over the past decade. While PD-1/PD-L1 inhibitors target the "effector" phase of T-cell activity, CTLA-4 blockade primarily enhances the "priming" phase of the immune response, occurring in lymph nodes where T-cells are first activated. This complementary mechanism is why IMJUDO is used in combination with durvalumab (an anti-PD-L1 antibody) rather than as a single agent, as the dual checkpoint blockade can produce synergistic anti-tumor effects.

Hepatocellular Carcinoma (Liver Cancer)

IMJUDO in combination with durvalumab (marketed as IMFINZI) is approved for the treatment of adult patients with advanced or unresectable hepatocellular carcinoma (HCC). This indication applies to patients whose liver cancer cannot be removed by surgery (unresectable) and may have spread within the liver or to other parts of the body. The approval was based on the HIMALAYA trial, a landmark phase III study that demonstrated a statistically significant improvement in overall survival with the combination of a single priming dose of tremelimumab plus durvalumab compared to sorafenib, the previous standard of care for first-line HCC treatment.

Hepatocellular carcinoma is the most common form of primary liver cancer and the third leading cause of cancer-related death worldwide. Many patients are diagnosed at an advanced stage when curative treatments such as surgical resection or liver transplantation are no longer feasible. The introduction of immune checkpoint inhibitor combinations has provided a new treatment paradigm for these patients, with IMJUDO plus durvalumab being one of the first immunotherapy regimens to demonstrate a significant overall survival benefit in this setting.

Non-Small Cell Lung Cancer

IMJUDO is also used in combination with durvalumab and platinum-based chemotherapy for the treatment of adult patients with metastatic non-small cell lung cancer (NSCLC) with no sensitizing EGFR mutations or ALK rearrangements. The POSEIDON trial demonstrated that adding tremelimumab to durvalumab plus chemotherapy improved progression-free survival compared to chemotherapy alone. This three-drug regimen offers a new option for patients who may not have adequate PD-L1 expression to benefit from durvalumab alone.

Lung cancer remains the leading cause of cancer-related mortality globally. Non-small cell lung cancer accounts for approximately 80-85% of all lung cancer cases. For patients with advanced disease, systemic therapy is the mainstay of treatment. The addition of CTLA-4 blockade to PD-L1 inhibition and chemotherapy represents an important step forward in the treatment of this disease, particularly for patients whose tumors do not express high levels of PD-L1.

What Should You Know Before Receiving IMJUDO?

Contraindications

IMJUDO must not be given to patients who are allergic (hypersensitive) to tremelimumab or to any of the other ingredients in this medicine. Hypersensitivity reactions, including anaphylaxis, have been reported with immune checkpoint inhibitors. If you have experienced a severe allergic reaction to any monoclonal antibody therapy in the past, be sure to inform your healthcare team before treatment begins. The inactive ingredients in IMJUDO include histidine, histidine hydrochloride monohydrate, trehalose dihydrate, disodium edetate dihydrate, polysorbat 80, and water for injections. Polysorbate 80 may cause allergic reactions in some individuals.

Warnings and Precautions

IMJUDO works by activating the immune system. As a consequence, the immune system may attack healthy tissues and organs, causing potentially serious and even life-threatening immune-mediated adverse reactions. Talk to your doctor before receiving IMJUDO if any of the following conditions apply to you:

• Autoimmune disease: If you have a condition where your immune system attacks your own body (such as rheumatoid arthritis, lupus, inflammatory bowel disease, or multiple sclerosis), IMJUDO may worsen these conditions.
• Organ transplant: If you have received an organ transplant, IMJUDO may increase the risk of organ rejection by enhancing immune activity.
• Lung problems: Pre-existing lung conditions may increase your risk of developing immune-mediated pneumonitis (lung inflammation).
• Liver problems: Since one indication for IMJUDO is liver cancer, many patients already have compromised liver function. Your doctor will carefully monitor your liver function throughout treatment.

During treatment with IMJUDO, your doctor will regularly monitor you for signs and symptoms of immune-mediated adverse reactions. These can affect virtually any organ system. Contact your doctor or seek emergency medical care immediately if you experience any of the following:

Children and Adolescents

IMJUDO should not be given to children and adolescents under 18 years of age. The safety and efficacy of tremelimumab have not been established in pediatric patients. Clinical trials have not been conducted in this population, and its use in children is not currently recommended by any major oncology guideline organization.

Drug Interactions

Tell your doctor about all medicines you are taking, have recently taken, or might take. This includes herbal remedies and over-the-counter medications. While tremelimumab is not metabolized by cytochrome P450 enzymes and is not expected to have traditional pharmacokinetic drug interactions, the combination immunotherapy regimen may interact with certain medications. Systemic corticosteroids or other immunosuppressive agents should generally be avoided before starting IMJUDO, as they may diminish the therapeutic effect. However, corticosteroids are used to manage immune-mediated adverse reactions once treatment has begun.

Pregnancy and Breastfeeding

IMJUDO is not recommended during pregnancy. Based on its mechanism of action, tremelimumab may cause harm to the developing fetus. CTLA-4 plays an important role in immune tolerance during pregnancy, and blocking this pathway could potentially lead to immune-mediated fetal rejection or other developmental complications. Women of childbearing potential must use effective contraception during treatment with IMJUDO and for at least 3 months after the last dose.

It is not known whether tremelimumab passes into breast milk. Because many antibodies are excreted in human milk and because of the potential for serious adverse reactions in breastfed infants, women are advised not to breastfeed during treatment with IMJUDO and for at least 3 months after the last dose. The decision to discontinue breastfeeding or to discontinue treatment should take into account the benefit of breastfeeding for the child and the benefit of therapy for the mother.

Driving and Using Machines

IMJUDO is unlikely to affect your ability to drive or use machines. However, if you experience side effects such as fatigue, dizziness, or any other symptoms that impair your concentration or reaction time, you should exercise caution when driving or operating machinery. Some immune-mediated reactions, such as endocrinopathies, may cause symptoms that affect alertness.

Sodium and Excipient Information

IMJUDO contains less than 1 mmol (23 mg) sodium per dose and is therefore essentially sodium-free. This medicine also contains polysorbate 80 (0.2 mg/ml), which may cause allergic reactions in some individuals. Tell your doctor if you have any known allergies to polysorbate-containing products.

How Does IMJUDO Interact with Other Drugs?

Tremelimumab is a fully human IgG2 monoclonal antibody that is cleared from the body primarily through catabolism (protein degradation) rather than through metabolic pathways involving cytochrome P450 enzymes. As a result, traditional pharmacokinetic drug-drug interactions are not expected. No formal drug interaction studies have been conducted with IMJUDO. However, there are several important pharmacodynamic considerations when using IMJUDO in combination with other medicines.

When IMJUDO is given in combination with durvalumab for liver cancer, the two agents work through complementary mechanisms. Tremelimumab blocks CTLA-4 to enhance T-cell priming, while durvalumab blocks PD-L1 to restore T-cell effector function at the tumor site. This dual checkpoint strategy has been shown to produce deeper and more durable anti-tumor responses than either agent alone in preclinical and clinical studies.

For the lung cancer indication, IMJUDO is combined with both durvalumab and platinum-based chemotherapy (such as carboplatin plus pemetrexed or paclitaxel). The chemotherapy component provides direct cytotoxic activity against cancer cells and may also enhance the immune response by releasing tumor antigens through immunogenic cell death. Patients receiving this triple combination should be aware that myelosuppression (low blood cell counts) is expected and will be monitored closely by the healthcare team.

What Is the Correct Dosage of IMJUDO?

IMJUDO is administered exclusively in a hospital or clinical setting under the supervision of a physician experienced in the treatment of cancer. It is given as an intravenous infusion (drip) into a vein over approximately 1 hour. The dosing regimen differs depending on the cancer type being treated. When IMJUDO is given in combination with durvalumab (and chemotherapy for lung cancer), IMJUDO is always administered first, followed by durvalumab, and then chemotherapy if applicable.

Dosage for Hepatocellular Carcinoma (Liver Cancer)

The single-dose approach for HCC is based on the HIMALAYA trial design, which demonstrated that a single priming dose of tremelimumab was sufficient to enhance the anti-tumor immune response when combined with ongoing durvalumab maintenance. This strategy, known as "STRIDE" (Single Tremelimumab Regular Interval Durvalumab), was specifically designed to maximize the benefit of CTLA-4 blockade during the initial priming phase while minimizing long-term immune-related toxicity.

Dosage for Non-Small Cell Lung Cancer

Children and Adolescents

IMJUDO has not been studied in patients under 18 years of age. There is no established dosing recommendation for pediatric patients. Use in children and adolescents is not recommended.

Missed Dose

It is very important that you do not miss a scheduled dose of IMJUDO. If you miss an appointment, contact your doctor immediately to reschedule. The timing of doses is carefully planned to optimize the immune response, and delays may affect treatment efficacy. Your oncologist will advise you on the best course of action if a dose is missed or delayed.

Overdose

Since IMJUDO is administered by healthcare professionals in a controlled clinical setting, overdose is unlikely. In clinical trials, no maximum tolerated dose has been identified. If an overdose occurs, the patient would be monitored closely for signs and symptoms of immune-mediated adverse reactions, and appropriate supportive treatment would be provided. There is no specific antidote for tremelimumab overdose.

What Are the Side Effects of IMJUDO?

Because IMJUDO activates the immune system, the side effects it causes are often related to immune overactivity. These immune-mediated adverse reactions can affect virtually any organ system in the body. Most immune-mediated side effects are manageable when detected early and treated promptly, usually with corticosteroids or other immunosuppressive agents. In some cases, treatment with IMJUDO may need to be delayed or permanently discontinued.

The side effect profile differs depending on whether IMJUDO is used in combination with durvalumab alone (for HCC) or with durvalumab plus platinum-based chemotherapy (for NSCLC). The addition of chemotherapy generally increases the incidence of hematologic side effects such as anemia, neutropenia, and thrombocytopenia. Below are the reported side effects organized by frequency for each combination regimen.

IMJUDO + Durvalumab (Liver Cancer)

IMJUDO + Durvalumab + Chemotherapy (Lung Cancer)

How Should IMJUDO Be Stored?

IMJUDO is administered in a hospital or clinical setting, and storage is the responsibility of healthcare professionals. Patients do not need to store this medicine at home. However, for completeness and transparency, the following storage requirements apply:

• Unopened vials: Store in a refrigerator at 2°C to 8°C (36°F to 46°F).
• Do not freeze: Freezing may damage the protein structure of the antibody and render it ineffective.
• Light protection: Store in the original packaging to protect from light.
• Shelf life: Do not use after the expiry date stated on the carton and vial label after EXP.
• Diluted solution: Use immediately. If not used immediately, total time from vial puncture to administration should not exceed 24 hours at 2°C to 8°C, or 12 hours at room temperature (up to 25°C/77°F).
• Visual inspection: Do not use if the solution is cloudy, discolored, or contains visible particles.
• Single use: IMJUDO is a single-dose vial. Any unused medicine remaining in the vial should be discarded.

Keep this medicine out of the sight and reach of children. Unused medicine and waste should be disposed of in accordance with local requirements for cytotoxic and biological waste.

What Does IMJUDO Contain?

Active Ingredient

Each milliliter of concentrate for solution for infusion contains 20 mg of tremelimumab. Tremelimumab is a fully human IgG2 monoclonal antibody produced in Chinese hamster ovary (CHO) cells by recombinant DNA technology.

• 25 mg vial: Contains 25 mg tremelimumab in 1.25 ml concentrate
• 300 mg vial: Contains 300 mg tremelimumab in 15 ml concentrate

Inactive Ingredients (Excipients)

• Histidine
• Histidine hydrochloride monohydrate
• Trehalose dihydrate
• Disodium edetate dihydrate
• Polysorbate 80
• Water for injections

Appearance and Packaging

IMJUDO concentrate for solution for infusion is a clear to slightly opalescent, colorless to slightly yellow solution that is preservative-free and free from visible particles. It is supplied in glass vials available in two sizes: one vial containing 1.25 ml of concentrate (25 mg) and one vial containing 15 ml of concentrate (300 mg). Not all pack sizes may be marketed in all countries.

Preparation and Administration (Healthcare Professionals)

IMJUDO must be prepared by qualified healthcare professionals using aseptic technique. The concentrate is visually inspected for particles and discoloration before use. The required volume is withdrawn from the vial and transferred to an intravenous infusion bag containing sodium chloride 9 mg/ml (0.9%) or glucose 50 mg/ml (5%) solution to prepare a diluted solution with a final concentration of 0.1 to 10 mg/ml. The diluted solution is administered intravenously over 1 hour through a sterile, low-protein-binding in-line filter of 0.2 or 0.22 micrometers. No other medicines should be administered simultaneously through the same infusion line.