Tremelimumab

Tremelimumab is a human monoclonal antibody used in cancer immunotherapy. It belongs to a class of medicines known as cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) inhibitors. CTLA-4 is a regulatory protein that limits the activation of T cells, which are immune cells involved in identifying and attacking abnormal cells. By binding to CTLA-4 and blocking its activity, tremelimumab helps increase T-cell activation and can strengthen the immune system’s response against cancer. This mechanism may also cause the immune system to attack healthy tissues, resulting in immune-related adverse reactions that require careful monitoring.

Tremelimumab is administered by intravenous infusion in a hospital or specialist oncology setting. It is generally used in combination with durvalumab, a programmed death-ligand 1 (PD-L1) inhibitor, and, for certain lung cancers, platinum-based chemotherapy. Its authorised uses in the United States and European Union include selected adults with unresectable hepatocellular carcinoma, a type of liver cancer, and metastatic non-small cell lung cancer without specified sensitising EGFR mutations or ALK genomic abnormalities. The treatment schedule depends on the cancer type and the accompanying medicines. Tremelimumab is not suitable for every patient with cancer, and treatment decisions depend on the diagnosis, disease characteristics, overall health and potential risks.

Tremelimumab was developed as a human immunoglobulin G2 monoclonal antibody targeting CTLA-4, an immune checkpoint involved in regulating T-cell activation. Its development followed research demonstrating that blocking immune checkpoints could strengthen antitumour immune responses. The medicine was initially investigated across several cancers, including melanoma, before its development advanced in combination with other immunotherapies. The United States Food and Drug Administration (FDA) approved tremelimumab-actl in October 2022 with durvalumab for adults with unresectable hepatocellular carcinoma. In November 2022, the FDA approved its use with durvalumab and platinum-based chemotherapy for selected adults with metastatic non-small cell lung cancer. The European Commission granted marketing authorisation for Imjudo in February 2023 for specified first-line liver and lung cancer indications. The HIMALAYA phase III clinical trial supported the liver cancer indication, while the POSEIDON phase III trial supported the lung cancer indication. These regulatory decisions established specific combination-treatment roles for tremelimumab rather than general use as a standalone anticancer medicine.

Tremelimumab is used in combination with other medicines for selected cancers. In adults with unresectable hepatocellular carcinoma, it is administered with durvalumab as an immune-based treatment regimen. In adults with metastatic non-small cell lung cancer, it is used with durvalumab and platinum-based chemotherapy when the tumour does not have sensitising EGFR mutations or ALK genomic abnormalities. The precise eligibility criteria and authorised indications may differ between countries. Tremelimumab is not routinely used as monotherapy under these approved indications, and it should not be assumed to be suitable for other cancers simply because they involve immune checkpoint pathways. Selection of treatment depends on cancer stage, previous therapy, tumour characteristics, liver function, general health and the patient's ability to tolerate immune-related adverse effects.

Tremelimumab is administered by intravenous infusion after dilution, under the supervision of an oncology team. For adults weighing at least 30 kg with unresectable hepatocellular carcinoma, the US-approved regimen consists of a single 300 mg dose given with durvalumab on the first treatment day, followed by durvalumab alone at four-week intervals. For patients weighing less than 30 kg, weight-based dosing is specified in the prescribing information. For metastatic non-small cell lung cancer, the regimen generally includes tremelimumab 75 mg every three weeks alongside durvalumab and platinum-based chemotherapy for four cycles, followed by a fifth tremelimumab dose with a later durvalumab dose according to the approved schedule. Weight-based alternatives apply to patients below the specified weight threshold. Infusion generally takes approximately 60 minutes. Treatment duration and continuation of accompanying medicines depend on the cancer type, the prescribed regimen, treatment response and tolerability. Doses should not be independently adjusted, delayed or repeated; the current local prescribing information must be followed.

Common side effects of tremelimumab-containing regimens include fatigue, skin rash, itching, diarrhoea, abdominal pain and muscle or joint pain. In lung cancer treatment regimens, nausea, reduced appetite and other effects associated with chemotherapy may also occur. Laboratory abnormalities can include changes in liver enzymes, bilirubin, sodium, haemoglobin and lymphocyte counts. The frequency and severity of these effects vary according to the treatment combination and individual patient factors. Some symptoms can be managed with supportive treatment under medical supervision, while others may indicate inflammation caused by immune system activation. Patients should report persistent diarrhoea, new rashes, worsening fatigue, abdominal symptoms or other new or unusual symptoms promptly rather than treating them without medical advice.

Tremelimumab can cause immune-mediated adverse reactions affecting almost any organ, sometimes during treatment or after the last dose. Important risks include inflammation of the bowel (colitis), liver (hepatitis), lungs (pneumonitis), kidneys (nephritis), thyroid and other endocrine glands, skin, nervous system and heart. Severe or potentially life-threatening reactions can occur even after a limited number of doses. Infusion-related reactions, severe skin reactions and complications associated with other medicines in the treatment regimen are also important considerations. Patients with underlying liver disease require particular attention because cancer-related symptoms and treatment-related liver inflammation can overlap. Depending on the severity and organ involved, clinicians may withhold treatment, prescribe corticosteroids or other immunosuppressive medicines, or permanently discontinue the relevant treatment regimen. Patients should seek urgent medical assessment for breathing difficulty, severe or persistent diarrhoea, jaundice, significant abdominal pain, confusion or other rapidly worsening symptoms.

Before treatment, clinicians should review the patient's medical history, including autoimmune disorders, previous organ or stem-cell transplantation, chronic infections, liver disease and previous immune checkpoint inhibitor therapy. Baseline assessments commonly include liver and kidney function, blood counts, thyroid function and other tests guided by the patient's condition. During treatment, laboratory monitoring and symptom assessment help identify immune-mediated complications early. Patients with active autoimmune disease or a history of organ transplantation may face additional risks that require specialist evaluation. Pregnancy should be discussed before treatment because immune checkpoint inhibition may harm a developing fetus; effective contraception is advised during treatment and for the period specified in the applicable prescribing information after the last dose. Breastfeeding is not recommended during treatment under the US prescribing information. Live vaccines should generally be avoided during immune checkpoint inhibitor treatment unless the treating specialist advises otherwise. Tremelimumab is a monoclonal antibody and is not primarily metabolised through conventional cytochrome P450 pathways, so classic metabolic drug interactions are less likely. Nevertheless, concomitant medicines, immunosuppressants and other anticancer therapies must be reviewed carefully.

Prescribers should confirm the cancer diagnosis, disease stage, treatment eligibility and the relevant locally approved regimen before initiating tremelimumab. Review baseline liver function, renal function, blood counts and thyroid status, with additional assessments guided by the patient's medical history. For hepatocellular carcinoma, distinguish possible immune-mediated hepatitis from underlying liver disease or cancer progression. Counsel patients and caregivers about early warning signs, particularly persistent diarrhoea, jaundice, cough, shortness of breath, severe rash and unusual fatigue. Explain that immune-related toxicities can develop after treatment has ended and should still be reported promptly. Pharmacists should verify the prescribed dose, body-weight requirements, treatment sequence, infusion preparation and compatibility with institutional procedures. Tremelimumab should be administered in an appropriately equipped healthcare setting, with observation for infusion reactions. Coordinate care among oncologists, pharmacists, nurses and relevant specialists to support timely investigations and management of adverse reactions. When severe immune-mediated toxicity occurs, follow the current prescribing information for treatment interruption, corticosteroid use and permanent discontinuation criteria.