What Is Tremelimumab-actl (Imjudo)? FDA Approval, Licensing in Türkiye, and Reimbursement Status

• FDA Approval: Yes (First approval date: October 21, 2022)
• Brand Name: Imjudo
• Active Ingredient: Tremelimumab-actl
• Administration: Intravenous infusion (IV)
• Class: Immune checkpoint inhibitor (Anti-CTLA-4 monoclonal antibody)
• Category: Antineoplastic / Immunotherapy
• Manufacturer: AstraZeneca
• Distribution in Türkiye: Not yet licensed in Türkiye.
• Cancers for Which It Is Approved: Advanced hepatocellular carcinoma (HCC), metastatic NSCLC (combination use)

What Is Imjudo? How Does It Work?

Imjudo (active ingredient: tremelimumab-actl) is a monoclonal antibody in the immunotherapy class, used particularly in cancer treatment. It is generally combined with durvalumab (Imfinzi) to treat certain advanced cancers.

How Does It Work?

Tremelimumab binds to and inhibits a receptor called CTLA-4 (Cytotoxic T-Lymphocyte Antigen-4) on T cells, which are immune system cells.

What normally happens?

• CTLA-4 acts as a ‘brake’ that suppresses T-cell activation.
• Cancer cells ‘escape’ the immune system by activating this braking mechanism.

What does Imjudo do?

• It binds to CTLA-4 and removes this braking mechanism.
• This reactivates T cells, allowing them to attack cancer cells.
• This restores the strength of the immune response in the tumor microenvironment.

Combination Therapy:

• Imjudo is generally given with another immunotherapy, durvalumab (anti-PD-L1).
• CTLA-4 and PD-L1 target different pathways, so using them together strengthens the immune system in multiple ways.
• This combination approach is known as ‘dual checkpoint blockade.’

FDA (US Food and Drug Administration) Approval History

• November 11, 2022 Approval: The use of Imfinzi and Imjudo with chemotherapy was approved in the US for patients with metastatic non-small cell lung cancer (NSCLC).
• October 24, 2022: FDA Approval: Imjudo (tremelimumab), in combination with Imfinzi, was approved by the FDA for patients with unresectable hepatocellular carcinoma (HCC).
• September 11, 2022: Data Presentation: Imfinzi and tremelimumab + chemotherapy nearly doubled 3-year survival in metastatic NSCLC, demonstrating a significant survival advantage over chemotherapy alone.
• April 25, 2022: FDA Priority Review: Tremelimumab with Imfinzi received priority review in the US for patients with unresectable liver cancer.
• October 15, 2021: HIMALAYA Phase III Results: Imfinzi + tremelimumab significantly improved overall survival in the 1st-line treatment of patients with unresectable liver cancer.
• September 9, 2021: Phase III Results: Imfinzi + tremelimumab + chemotherapy improved progression-free survival by 28% and overall survival by 23% in patients with stage IV NSCLC.
• May 7, 2021: POSEIDON Study: The combination of Imfinzi and tremelimumab + chemotherapy demonstrated an overall survival advantage in patients receiving 1st-line treatment for stage IV NSCLC.
• February 5, 2021: KESTREL Study Update: Imfinzi and/or tremelimumab were investigated as 1st-line treatment for recurrent/metastatic head and neck cancer.
• March 6, 2020: DANUBE Study Update: Imfinzi and tremelimumab were studied for stage IV unresectable bladder cancer.
• January 20, 2020: Orphan Drug Designation: Imfinzi and tremelimumab received ‘orphan drug’ status in the US for liver cancer treatment.
• August 21, 2019: NEPTUNE Study Update: An update was presented from the Phase III study investigating Imfinzi + tremelimumab in patients with stage IV NSCLC.

Licensing in Türkiye

This drug was licensed in Türkiye on 20.03.2025. 

Therapeutic Indications 

IMJUDO, in combination with durvalumab and platinum-based chemotherapy, is indicated for the first-line treatment of adults with ECOG 0-1 metastatic nonsquamous non-small cell lung cancer (NSCLC) without sensitizing epidermal growth factor receptor (EGFR) mutations or anaplastic lymphoma kinase (ALK) translocations. At least 12 months must have elapsed after completion of adjuvant chemotherapy in early-stage patients or chemoradiotherapy in locally advanced patients.

There is no SGK reimbursement. Cost of a Single 300 mg Vial: Approximately 1,420,000 TL - 1,450,000 TL.

Resistance Mechanisms

Increased Immunosuppressive Cells in the Tumor Microenvironment

• Regulatory T cells (Tregs) and MDSCs (myeloid-derived suppressor cells) increase, suppressing the immune system.
• Even if tremelimumab activates T cells, the response remains insufficient because of these suppressor cells.

Impaired Antigen Presentation in the Tumor

• Cancer cells or antigen-presenting cells (APCs) may reduce MHC class I expression, or costimulatory signals may be impaired.
• In this situation, activated T cells cannot recognize or bind to tumor cells.

Inflammatory Cytokine Imbalance

• An increase in suppressive cytokines such as IL-10 and TGF-β in the tumor microenvironment weakens the immune response.
• Tremelimumab’s effect is blunted in this suppressive environment.

Increased PD-L1 Expression

• Tumor cells or immune cells may increase PD-L1 levels after CTLA-4 blockade.
• This reduces the response without simultaneous PD-L1 inhibition (for example, without durvalumab).

T-Cell Deficiency or Exhaustion

• T cells exposed to continuous antigen stimulation lose their function.
• Tremelimumab cannot activate these cells because they are irreversibly exhausted.

Genetic and Epigenetic Changes

• Mutations arising in tumor cells may activate escape pathways outside the CTLA-4 pathway.
• These changes may make immune evasion permanent.

Absorption

• It is administered by intravenous (IV) infusion, bypassing absorption; the entire drug dose enters the systemic circulation directly.
• Administration time: A 60-minute infusion.

Distribution

• Volume of distribution (Vd): Approximately 15–20 liters
• This indicates that tremelimumab remains primarily in the intravascular and interstitial fluid compartments.
• Plasma protein binding is high.
• Tissue penetration is limited, but it can reach lymph nodes and the tumor microenvironment.

Metabolism

• Tremelimumab is not metabolized by liver enzymes (for example, CYP450 enzymes).
• Like other IgG1 monoclonal antibodies, it is broken down through the body’s natural protein degradation mechanisms (in the reticuloendothelial system).
• Enzymatic hydrolysis (lysosomal proteolysis) is involved in degradation.

Elimination

• Half-life (t1/2): Approximately 22 days
• Elimination occurs through the reticuloendothelial system and phagocytosis rather than conventional renal or hepatic routes.
• Therefore, its pharmacokinetics do not change substantially in hepatic or renal impairment.

Dosing Schedule

Unresectable Hepatocellular Carcinoma

Imjudo is generally used with durvalumab (Imfinzi). This combination is known as the ‘STRIDE’ regimen. In this regimen, Imjudo is administered only once. This single dose is 300 mg, given as an intravenous (IV) infusion over approximately 60 minutes. The patient then continues treatment with durvalumab monotherapy (1500 mg IV every 4 weeks).

Metastatic Non-Small Cell Lung Cancer

Imjudo is used with durvalumab and platinum-based chemotherapy. Here, Imjudo is administered at a lower dose but on multiple occasions. The recommended dose is 75 mg intravenously every 3 weeks for a total of 4 doses. It is given concurrently with platinum-based chemotherapy during the first 4 cycles. Durvalumab then continues alone as maintenance treatment (1500 mg IV every 4 weeks).

Mandatory premedication is generally not recommended before Imjudo administration. However, premedication may be given at the physician’s discretion against rare infusion-related reactions, particularly in patients previously sensitive to similar immunotherapies. This may generally involve a mild antihistamine (such as diphenhydramine), an antipyretic (acetaminophen), or a low-dose corticosteroid. The decision should be individualized according to the patient’s clinical history.

Drug Interactions

• Does Not Affect Liver Enzymes: Because tremelimumab is not metabolized by hepatic enzymes such as CYP3A4 or CYP2D6, it does not have conventional interactions with drugs affecting these enzymes. This means that many medications can be used together safely.
• Combination with Immunosuppressive Drugs Is Inadvisable:Tremelimumab works by activating the immune system. Concurrent use with systemic corticosteroids (e.g., prednisone, dexamethasone) or other immunosuppressants (e.g., cyclosporine, tacrolimus) is therefore not recommended, as these drugs may weaken tremelimumab’s immunostimulatory effect.
• Vaccine Interactions: Live virus vaccines (e.g., yellow fever, measles, mumps, BCG) are not recommended during or shortly after tremelimumab treatment. Changes in the immune system may increase infection risk or reduce vaccine effectiveness.
• Combination with Other Immunotherapies: Tremelimumab is generally administered with durvalumab (anti-PD-L1). This combination targets complementary immune pathways and provides a synergistic effect. Its use with other immunotherapies should, however, be evaluated only in clinical trials.
• Supportive Medications Before Infusion: Some patients may receive premedications such as antihistamines or antipyretics before tremelimumab infusion to address allergic reaction risk. No serious interaction with these drugs is expected.

Precautions

Immune-Related Side Effects (Immune-Mediated Toxicities)

Because tremelimumab activates T cells, attacks on the body’s own tissues can cause inflammatory reactions in various organs:

• Pneumonitis: (Lung inflammation) breathlessness, cough, fever
• Colitis: (Bowel inflammation) diarrhea, abdominal pain, bloody stools
• Hepatitis: (Liver inflammation) right upper abdominal pain, jaundice, elevated transaminases
• Endocrinopathies: (Thyroid, pituitary, or adrenal dysfunction) fatigue, weight changes, headache, hypotension
• Nephritis: (Kidney inflammation) increased creatinine, impaired kidney function
• Dermatological reactions: Rash, itching, rarely severe skin eruptions
• Pancreatitis: Rare inflammation of the pancreas

These effects are generally treated with corticosteroids. Early diagnosis and prompt intervention are important.

Infusion Reactions

During intravenous administration:

• Chills, fever, dizziness, weakness, or anaphylaxis may develop.

Although generally mild and temporary, serious reactions may require the infusion to be stopped.

Embryo-Fetal Toxicity

• Use during pregnancy is not recommended. The CTLA-4 pathway is important for embryonic immune tolerance.
• Women of childbearing potential should use effective contraception throughout treatment and for at least 3 months afterward.

Concurrent Steroid or Immunosuppressant Use

• Systemic corticosteroids (e.g., prednisone) or immunosuppressive drugs may weaken tremelimumab’s effects on the immune system.
• They should not be used together unless necessary.

 Vaccination

• Live virus vaccines must not be administered during treatment or for a certain period afterward.
• Inactivated (killed) vaccines should be preferred, and the immune response may be reduced.

 Laboratory Monitoring

The following parameters should be monitored regularly before and during treatment:

• Liver function tests (AST, ALT, bilirubin)
• Kidney function tests (creatinine)
• Thyroid hormones (TSH, fT4)
• Complete blood count (anemia, leukopenia, low lymphocytes)

Side Effects

• Increased AST: 30%
• Increased ALT: 28%
• Low hemoglobin: 25%
• Rash: 24%
• Low sodium: 22%
• Diarrhea: 20%
• Fatigue: 19%
• Increased bilirubin: 18%
• Itching (pruritus): 16%
• Musculoskeletal pain: 15%
• Increased alkaline phosphatase: 15%
• Abdominal pain: 14%
• Nausea: 13%
• Low lymphocytes: 13%
• Vomiting: 10%
• Fever: 10%
• Headache: 9%
• Joint pain (arthralgia): 8%
• Hypothyroidism: 7%