Your web browser is no longer supported by Microsoft. CAS number: 745013-59-6. Tremelimumab plus durvalumab demonstrated a statistically significant and clinically meaningful improvement in OS compared to sorafenib (stratified hazard ratio [HR] of 0.78 [95% CI: 0.66, 0.92], 2-sided p value = 0.0035); median OS was 16.4 months (95% CI: 14.2, 19.6) versus 13.8 months (95% CI: 12.3, 16.1). Other Immune-Mediated Adverse Reactions: The following clinically significant, immune-mediated adverse reactions occurred at an incidence of less than 1% each in patients who received tremelimumab-actl in combination with durvalumab or were reported with the use of other immune-checkpoint inhibitors. Retrieved on November 14, 2019, from https://www.clinicaltrials.gov/ct2/show/NCT03075527, United States National Library of Medicine. Topical emollients and/or topical corticosteroids may be adequate to treat mild to moderate non-exfoliative rashes. Withhold or permanently discontinue IMFINZI and IMJUDO depending on severity. IMFINZI and IMJUDO are registered trademarks and AstraZeneca Access 360 is a trademark of the AstraZeneca group of companies. Written by Immune-mediated hepatitis occurred in 2.8% (52/1889) of patients receiving IMFINZI, including fatal (0.2%), Grade 4 (0.3%) and Grade 3 (1.4%) adverse reactions. Monoclonal antibody drugs for cancer: How they work. Accessed November 2022. Tremelimumab granted Orphan Drug Designation by US FDA for treatment of malignant mesothelioma. The study concluded is estimated to be completed in late 2019. Interrupt, slow the rate of, or permanently discontinue tremelimumab-actl and durvalumab based on the severity. Advise females of reproductive potential that tremelimumab-actl can cause harm to a fetus and to inform their healthcare provider of a known or suspected pregnancy. For platinum-based chemotherapy or pemetrexed, refer to Prescribing Information for administration information Observe for 60 minutes following completion of infusion; then administer durvalumab as a separate IV infusion over 60 minutes on same day Combination with durvalumab: Infuse tremelimumab, followed by durvalumab on same day of dosing Follow patients closely for evidence of transplant-related complications and intervene promptly. Events resolved in 3 of the 5 patients and resulted in permanent discontinuation in 1 patient. Access free resources to help you or a loved one after a mesothelioma diagnosis. She hopes to create public awareness about cancer through her writing. Medically reviewed by Drugs.com on Nov 29, 2022. Interaction highlights: Please see product labeling for drug interaction information. The most common (20%) adverse reactions occurring in patients were rash, diarrhea, fatigue, pruritis, musculoskeletal pain and abdominal pain. Research is ongoing to determine which mesothelioma patients may benefit the most from this drug. Lancet, 18(9), 1261-1273. doi: 10.1016/S1470-2045(17)30446-1, Kindler, H.L. Pancreatitis: Advise patients to contact their healthcare provider immediately for signs or symptoms of pancreatitis. This material is provided for educational purposes only and is not intended for medical advice, diagnosis or treatment. Retrieved March 4, 2023, from https://www.asbestos.com/treatment/immunotherapy/tremelimumab/. Retrieved on November 14, 2019, from https://clinicaltrials.gov/ct2/show/record/NCT02592551?view=record. Withhold or permanently discontinue tremelimumab-actl and durvalumab depending on severity. Initiate hormone replacement therapy for hypothyroidism or institute medical management of hyperthyroidism as clinically indicated. Tremelimumab is considered an immune checkpoint blocker because it blocks a protein called CTLA-4, which deactivates killer T cells. Purpose: This phase I/II study evaluated tremelimumab (anticytotoxic T-lymphocyte-associated antigen-4 monoclonal antibody) and durvalumab (antiprogrammed death ligand-1 monoclonal antibody) as monotherapies and in combination for patients with unresectable hepatocellular carcinoma (HCC), including a novel regimen featuring a Immune-mediated nephritis occurred in 1% (4/388) of patients receiving IMFINZI and IMJUDO, including Grade 3 (0.5%) adverse reactions. We will help you find the best mesothelioma doctor in your area. Patients were randomized to one of three arms: tremelimumab 300 mg as a one-time single intravenous (IV) infusion plus durvalumab 1500 mg IV on the same day, followed by durvalumab 1500 mg IV every 4 weeks; durvalumab 1500 mg IV every 4 weeks; or sorafenib 400 mg orally twice daily until disease progression or unacceptable toxicity. The recommended tremelimumab dose for patients weighing 30 kg or more is 300 mg IV as a single dose in combination with durvalumab 1500 mg at Cycle 1/Day 1, followed by durvalumab 1500 mg IV every 4 weeks. 2. Borrie, A., & Vareki, M. (2018). Interrupt, slow the rate of, or permanently discontinue IMFINZI and IMJUDO based on the severity. Clinical trials often combine the medication with another immunotherapy drug called durvalumab. IMFINZI and IMJUDO can cause immune-mediated pneumonitis, which may be fatal. Of the 393 patients with uHCC treated with tremelimumab-actl in combination with durvalumab, 50% of patients were 65 years or older and 13% of patients were 75 years or older. Tremelimumab Dosage and Administration General. The largest study to date of tremelimumab in mesothelioma patients did not reach its goal of extending overall survival. This Immune-mediated thyroiditis occurred in 1.2% (7/596) of patients receiving IMFINZI in combination with IMJUDO and platinum-based chemotherapy. Consider administration of other systemic immunosuppressants in patients whose immune-mediated adverse reactions are not controlled with corticosteroid therapy. Calling this number connects you with a Patient Advocate at The Mesothelioma Center, the nation's most trusted mesothelioma resource. An orphan drug typically treats uncommon illnesses, and cannot make much of a profit. Advise females of reproductive potential to use effective contraception during treatment with tremelimumab-actl and for 3 months after the last dose of the drug. She graduated with a Bachelor of Arts degree from the University of Illinois at Chicago, where she majored in communication and minored in sociology. In patients with Stage III NSCLC in the PACIFIC study receiving IMFINZI (n=475), the most common adverse reactions (20%) were cough (40%), fatigue (34%), pneumonitis or radiation pneumonitis (34%), upper respiratory tract infections (26%), dyspnea (25%), and rash (23%). WebOut of more than 180 oncology approvals, less than half of the approvals were successfully converted to full FDA approvals so far. For more information, visit our sponsors page. Immediate treatment of side effects helps keep them in control. Systemic corticosteroids were required in all 9 patients and of these, 7 patients required high-dose corticosteroid treatment (at least 40 mg prednisone or equivalent per day). Serious adverse reactions occurred in 44% of patients, with the most frequent serious adverse reactions reported in at least 2% of patients being pneumonia (11%), anemia (5%), diarrhea (2.4%), thrombocytopenia (2.4%), pyrexia (2.4%), and febrile neutropenia (2.1%). (2017, December 13). Update your browser for more security, speed and compatibility. Retrieved from, ClinicalTrials.gov. Advise the patient to read the FDA-approved patient labeling (Medication Guide). Once an antibody attaches to an antigen on a molecule, receptors signal the immune system to fight back. This phase 2 trial conducted by the Dana-Farber Cancer Institute studies how well durvalumab with or without tremelimumab works in treating pleural mesothelioma patients who are eligible for tumor-removing surgery. CTLA-4 plays a role in maintaining maternal immune tolerance to the fetus to preserve pregnancy and in immune regulation of the newborn. Last modified February 24, 2023. https://www.asbestos.com/treatment/immunotherapy/tremelimumab/. Tremelimumab blocks the activity of CTLA-4, contributing to T-cell activation, priming the immune response to cancer and fostering cancer cell death. Mechanism of action. Tremelimumab aims to stimulate an immune system attack on tumors. Cytotoxic T lymphocytes (CTLs) can recognize and destroy cancer cells. However, there is also an inhibitory mechanism (immune checkpoint) that interrupts this destruction. Current clinical trials are testing the drug on multiple types of cancer. Withhold or permanently discontinue tremelimumab-actl in combination with durvalumab based on the severity. Clinical trials began testing tremelimumab on mesothelioma in 2013. (2015, October 27). For more information, visit our sponsor page. Evaluate clinical chemistries including liver enzymes, creatinine, adrenocorticotropic hormone (ACTH) level, and thyroid function at baseline and before each dose. Orphan drug designation is not the same as FDA approval, but it does help pharmaceutical companies move a drug designed to treat rare diseases through the approval process. Immune-mediated hypothyroidism occurred in 11% (42/388) of patients receiving IMFINZI and IMJUDO. Tremelimumab, which has no brand name yet, has not been approved by the United States Food and Drug Administration (FDA) to treat any cancer or disease. 0 Tremelimumab as second- or third-line treatment of unresectable malignant mesothelioma (MM): Results from the global, double-blind, placebo-controlled DETERMINE study. Tremelimumab-actl is a monoclonal antibody that binds to CTLA-4 and blocks the interaction with its ligands CD80 and CD86, releasing CTLA-4-mediated inhibition of T-cell activation. Tremelimumab may help people live longer with mesothelioma, but the drug may also cause side effects. Retrieved on November 14, 2019, from https://www.mayoclinic.org/diseases-conditions/cancer/in-depth/monoclonal-antibody/art-20047808, National Cancer Institute. Grade 3 hypophysitis/hypopituitarism occurred in <0.1% (1/1889) of patients who received IMFINZI. product information is intended for US Healthcare Professionals only. See full Prescribing Information for preparation and administration instructions and dosage modifications for adverse reactions. Systemic corticosteroids were required in all patients with immune-mediated nephritis, of these 3 patients required high-dose corticosteroid treatment (at least 40 mg prednisone or equivalent per day). Patients taking the medication can receive medications or therapies to treat each side effect or keep them under control. Tremelimumab succeeds by activating immune cells, called cytotoxic T lymphocytes (CTLs), or killer T cells, which kill cancer cells. Helps more than 50% of mesothelioma patients diagnosed annually in the U.S. A+ rating from the Better Business Bureau. Infusion-related reactions occurred in 2.2% (42/1889) of patients receiving IMFINZI, including Grade 3 (0.3%) adverse reactions. Immune-mediated hyperthyroidism occurred in 5% (30/596) of patients receiving IMFINZI in combination with IMJUDO and platinum-based chemotherapy, including Grade 3 (0.2%) adverse reactions. Clinical trials of tremelimumab have shown it may help control several different types of cancer including lung cancer and mesothelioma. All rights reserved. Cytomegalovirus (CMV) infection/reactivation has been reported in patients with corticosteroid-refractory immune-mediated colitis. See USPI Dosing and Administration for specific details. All patients received systemic corticosteroids, and 20 of the 23 patients received high-dose corticosteroid treatment (at least 40 mg prednisone or equivalent per day). Please see Full Prescribing Information including Medication Guide for IMFINZI and IMJUDO. WebThe most common side effects of IMFINZI when used with other anticancer medicines in people with biliary tract cancer (BTC) include feeling tired, nausea, constipation, decreased appetite, stomach (abdominal) pain, rash, and fever. Other (hematologic/immune): Hemolytic anemia, aplastic anemia, hemophagocytic lymphohistiocytosis, systemic inflammatory response syndrome, histiocytic necrotizing lymphadenitis (Kikuchi lymphadenitis), sarcoidosis, and immune thrombocytopenia. Monitor for signs and symptoms that may be clinical manifestations of underlying immune-mediated adverse reactions. Infusion-related reactions occurred in 2.9% (17/596) of patients receiving IMFINZI in combination with IMJUDO and platinum-based chemotherapy, including Grade 3 (0.3%) adverse reactions. On October 21, 2022, the Food and Drug Administration approved tremelimumab (Imjudo, AstraZeneca Pharmaceuticals) in combination with durvalumab for adult patients with unresectable hepatocellular carcinoma (uHCC). Fatal adverse reactions occurred in a total of 4.2% of patients, In patients with extensive-stage SCLC in the CASPIAN study receiving IMFINZI plus chemotherapy (n=265), the most common adverse reactions (20%) were nausea (34%), fatigue/asthenia (32%), and alopecia (31%). This approval is based on a comparison of the 782 patients randomized to tremelimumab plus durvalumab to sorafenib. In cases of suspected immune-mediated adverse reactions, initiate appropriate workup to exclude alternative etiologies, including infection. There are no available data on the use of tremelimumab-actl in pregnant women. By blocking CTLA-4, tremelimumab activates killer T cells so they can get to work fighting cancer. WebTremelimumab is a fully human monoclonal antibody that binds to the CTLA-4 molecule. al. Events resolved in 15 of the 18 patients. Tremelimumab-actl is approved to treat adults with: Hepatocellular carcinoma (a type of liver cancer) that cannot be removed by surgery. Tremelimumab is an immunotherapy drug that helps the immune system block cancerous cells. Immune-Mediated Adrenal Insufficiency: Tremelimumab-actl in combination with durvalumab can cause primary or secondary adrenal insufficiency. For Grade 1 or 2 infusion-related reactions, consider using pre-medications with subsequent doses. If receiving both durvalumab and tremelimumab for the first 4 cycles, they will be given on the same day. CTLA-4 is a negative regulator of T-cell activity. Retrieved from, National Cancer Institute. Immune-mediated hypothyroidism occurred in 8.6% (51/596) of patients receiving IMFINZI in combination with IMJUDO and platinum-based chemotherapy, including Grade 3 (0.5%) adverse reactions. The incidence of pneumonitis is higher in patients who have received prior thoracic radiation. AstraZenecas Biologics License Application (BLA) for tremelimumab has been accepted for Priority Review in the US, supporting the indication of a single priming dose of the anti-CTLA4 antibody added to Imfinzi (durvalumab) for the treatment of patients with unresectable hepatocellular carcinoma (HCC).A supplemental BLA (sBLA) has also (2009, November 19). In reproduction studies, administration of tremelimumab-actl to pregnant cynomolgus monkeys during the period of organogenesis through delivery was not associated with maternal toxicity or effects on embryo-fetal development at exposure levels approximately 31-times higher than those observed at a recommended dose of 300 mg (based on AUC). After several months, the drug seems to stop working altogether, which is why the FDA hasnt improved it. The .gov means its official.Federal government websites often end in .gov or .mil. Immune-mediated hyperthyroidism occurred in 2.1% (39/1889) of patients receiving IMFINZI. In addition to being investigated as a monotherapy treatment for patients with mesothelioma, tremelimumab is currently being studied in combination with Maternal IgG is known to be present in human milk. Type 1 Diabetes Mellitus: Monitor patients for hyperglycemia or other signs and symptoms of diabetes. IMFINZI in combination with IMJUDO can cause immune-mediated pancreatitis. Webof tremelimumab-actl* at Day 1 of Cycle 1, followed by a maintenance dose of 20 mg/kg as a single agent every 28 days thereafter, until disease 1. Tremelimumab for the treatment of malignant mesothelioma. This is a staff of compassionate and knowledgeable individuals who respect what your family is experiencing and who go the extra mile to make an unfortunate diagnosis less stressful. View full prescribing information for Imjudo. Immune-mediated adrenal insufficiency occurred in 0.5% (9/1889) of patients receiving IMFINZI, including Grade 3 (<0.1%) adverse reactions. (2016). WebIMFINZI is indicated for the treatment of adult patients with unresectable Stage III non-small cell lung cancer (NSCLC) whose disease has not IMPORTANT SAFETY INFORMATION There are no contraindications for IMFINZI (durvalumab) or IMJUDO (tremelimumab-actl). About tremelimumab Tremelimumab is a human monoclonal antibody and potential new medicine that targets the activity of cytotoxic T-lymphocyte-associated WebTremelimumab is an investigational, fully human IgG monoclonal antibody directed against CTLA-4, a coinhibitory receptor that represses effector T-cell activity in cancer. Monitor for signs and symptoms of infusion-related reactions. However, a phase III trial of tremelimumab mo AHFSfirstRelease. Tremelimumab-actl, a cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) blocking antibody, is an antineoplastic agent. Cardiac/vascular: Myocarditis, pericarditis, vasculitis. Based on its mechanism of action, fetal exposure to tremelimumab-actl may increase the risk of developing immune-mediated disorders or altering the normal immune response. (2006). Download our guide to get the latest information about mesothelioma treatments, clinical trials, complementary and emerging therapies. Imfinzi combinations have also demonstrated clinical benefit in metastatic NSCLC in the POSEIDON Phase III trial. Imjudo (tremelimumab) is a human monoclonal antibody that targets the activity of cytotoxic T-lymphocyte-associated protein 4 (CTLA-4). It has been shown to induce durable tumor responses in patients with metastatic melanoma For non-prescription products, read the label or package ingredients carefully. The tremelimumab antibody activates an immune cell known as cytotoxic T lymphocytes (CTLs), or killer T cells. Tremelimumab is a cytotoxic agent that works to decrease tumour growth. Immune-Mediated Nephritis with Renal Dysfunction: Tremelimumab-actl in combination with durvalumab can cause immune-mediated nephritis.