tremelimumab package insert

These complications may occur despite intervening therapy between PD-1/L-1 blockade and allogeneic HSCT. Efficacy and safety of an intensified schedule of tremelimumab for chemotherapy-resistant malignant mesothelioma: an open-label, single-arm, phase 2 study. Immune-mediated Type 1 diabetes mellitus occurred in 0.5% (3/596) of patients receiving IMFINZI in combination with IMJUDO and platinum-based chemotherapy including Grade 3 (0.3%) adverse reactions. The .gov means its official.Federal government websites often end in .gov or .mil. Our team has a combined experience of more than 30 years in assisting cancer patients, and includes a medical doctor, an oncology registered nurse and a U.S. Navy veteran. Hypophysitis can present with acute symptoms associated with mass effect such as headache, photophobia, or visual field cuts. Last Modified: September 22, 2022, Created: July 6, 2022. For Grade 2 or higher adrenal insufficiency, initiate symptomatic treatment, including hormone replacement as clinically indicated. Immune-mediated hypophysitis occurred in 1.3% (8/596) of patients receiving IMFINZI in combination with IMJUDO and platinum-based chemotherapy, including Grade 3 (0.5%) adverse reactions. This optimistic outcome has researchers hopeful for similar results for mesothelioma patients. Median PFS was 3.8 months (95% CI: 3.7, 5.3) and 4.1 months (95% CI: 3.7, 5.5) for the tremelimumab plus durvalumab and sorafenib arms, respectively (stratified HR 0.90; 95% CI: 0.77, 1.05). Cytomegalovirus (CMV) infection/reactivation has been reported in patients with corticosteroid-refractory immune-mediated colitis. IMFINZI, in combination with gemcitabine and cisplatin, is indicated for the treatment of adult patients with locally advanced or metastatic biliary tract cancer (BTC). IMFINZI and IMJUDO can cause severe or life-threatening infusion-related reactions. However, combining tremelimumab and durvalumab has proven more effective against lung cancer than tremelimumab alone. Intestinal perforation and large intestine perforation were reported in 0.1% of patients. 322 0 obj <>/Filter/FlateDecode/ID[<2567B33F55498047B5C633564638CC02>]/Index[301 165]/Info 300 0 R/Length 115/Prev 474568/Root 302 0 R/Size 466/Type/XRef/W[1 3 1]>>stream The drugs stopped his tumor growth for months. Important immune-mediated adverse reactions listed under Warnings and Precautions may not include all possible severe and fatal immune-mediated reactions. IMFINZI in combination with IMJUDO can cause immune-mediated pancreatitis. Advise pregnant women and females of reproductive potential of the potential risk to a fetus. Medically reviewed by Drugs.com on Nov 29, 2022. Mesothelioma Center - Vital Services for Cancer Patients & Families doesnt believe in selling customer information. Retrieved from, National Cancer Institute. Retrieved from, Guazzelli, A. 1 Tremelimumab caused increased IL-2 production in a dose-dependent manner in ex-vivo blood stimulation assays using peripheral blood The recommended tremelimumab dose for patients weighing 30 kg or more is 75 mg IV every 3 weeks with durvalumab 1500 mg IV and platinum-based chemotherapy for 4 cycles, then durvalumab 1500 mg with maintenance chemotherapy every 4 weeks. A fifth tremelimumab dose (75 mg) should be given at week 16. Tremelimumab-actl is available in the following dosage form(s) and strength(s): Injection: 25 mg/1.25 mL (20 mg/mL) solution in Fatal and other serious complications can occur in patients who receive allogeneic hematopoietic stem cell transplantation (HSCT) before or after being treated with a PD-1/L-1 blocking antibody. ORR was 20.1% (95% CI: 16.3, 24.4) in the tremelimumab plus durvalumab arm and 5.1% (95% CI: 3.2, 7.8) for those treated with sorafenib. Initiate treatment with insulin as clinically indicated. Immune-Mediated Pneumonitis: Tremelimumab-actl in combination with durvalumab can cause immune-mediated pneumonitis, which may be fatal. Researchers suggested more trials that combine drugs are necessary to see how well tremelimumab may work against mesothelioma. Karen Selby joined Asbestos.com in 2009. Events resolved in 2 of the 6 patients. IMFINZI, in combination with etoposide and either carboplatin or cisplatin, is indicated for the first-line treatment of adult patients with extensive-stage small cell lung cancer (ES-SCLC). Small studies indicate about half of mesothelioma patients respond to tremelimumab and about half live at least one year on the drug. Follow patients closely for evidence of transplant-related complications and intervene promptly. Invert vial gently several times before use to ensure uniformity of the emulsion prior to Tremelimumab-actl works as a form of immunotherapy and blocks the activity of T-lymphocyte-associated- antigen 4 (CTLA-4) a molecule found on T cells that Pharmacodynamics. For assistance with single-patient INDs for investigational oncology products, healthcare professionals may contact OCEs Project Facilitate at 240-402-0004 or email OncProjectFacilitate@fda.hhs.gov. (2006). 5 WARNINGS AND PRECAUTIONS 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%). Tremelimumab blocks the activity of CTLA-4, contributing to T-cell activation, priming the immune response to cancer and fostering cancer cell death. (n.d.). Healthcare professionals should report all serious adverse events suspected to be associated with the use of any medicine and device to FDAsMedWatch Reporting System or by calling 1-800-FDA-1088. Immune mediated pneumonitis occurred in 1.3% (5/388) of patients receiving tremelimumab-actl in combination with durvalumab, including fatal (0.3%) and Grade 3 (0.2%) adverse reactions. Around half of the patients lived at least a year in both studies. 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 purpose of tremelimumab is to blog receptors on immune cells that normally suppress immune attacks. Institute medical management promptly, including specialty consultation as appropriate. Asbestos.com is sponsored by law firms. Systemic corticosteroids were required in 2 patients (2/6) with immune-mediated thyroiditis, of these 1 patient required high-dose corticosteroid treatment (at least 40 mg prednisone or equivalent per day). Withhold or permanently discontinue tremelimumab-actl in combination with durvalumab depending on severity. MEDI4736 or MEDI4736 + Tremelimumab in Surgically Resectable Malignant Pleural Mesothelioma, https://www.sciencedirect.com/science/article/abs/pii/S2213260021000436, https://www.cancer.gov/publications/dictionaries/cancer-drug?cdrid=448620, https://www.astrazeneca.com/media-centre/press-releases/2015/tremelimumab-orphan-drug-designation-us-fda-malignant-mesothelioma-treatment-15042015.html, https://www.astrazeneca.com/our-science/pipeline.html, https://web.archive.org/web/20150905112429/https://www.pfizer.com/system/files/products/material_safety_data/PZ00158.pdf, https://clinicaltrials.gov/ct2/show/NCT02592551, https://www.clinicaltrials.gov/ct2/show/NCT02588131, https://clinicaltrials.gov/ct2/show/study/NCT01843374, https://www.clinicaltrials.gov/ct2/show/NCT03075527, Immune checkpoint blocker, monoclonal antibody, Ticilimumab, anti-CTLA 4 monoclonal antibody-Pfizer, CP-675, CP-675206, Skin reaction, skin rash, itching sensation, diarrhea, nausea, fatigue and immune-mediated disorders. 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. 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. "Tremelimumab." This The most frequent serious adverse reactions reported in at least 1% of patients were febrile neutropenia (4.5%), pneumonia (2.3%), anemia (1.9%), pancytopenia (1.5%), pneumonitis (1.1%), and COPD (1.1%). Musculoskeletal and connective tissue disorders: Myositis/polymyositis, rhabdomyolysis and associated sequelae including renal failure, arthritis, polymyalgia rheumatica. Thyroid Disorders: Tremelimumab-actl in combination with durvalumab can cause immune-mediated thyroid disorders. It is essential that the manufacturer's labeling be consulted for more detailed information on usual uses, dosage and administration, cautions, precautions, contraindications, potential drug interactions, laboratory test interferences, and acute toxicity. et al. Filing Veterans Benefits for Mesothelioma, COVID-19 Information for Mesothelioma Patients, https://www.sciencedirect.com/topics/neuroscience/tremelimumab, https://www.mayoclinic.org/diseases-conditions/cancer/in-depth/monoclonal-antibody/art-20047808, https://www.cancer.gov/about-cancer/treatment/clinical-trials/intervention/tremelimumab?redirect=true, https://www.cancer.gov/publications/dictionaries/cancer-drug/def/tremelimumab, http://theoncologist.alphamedpress.org/content/12/7/873.full, https://www.clinicaltrials.gov/ct2/show/NCT03075527, https://clinicaltrials.gov/ct2/show/NCT01843374, https://clinicaltrials.gov/ct2/show/record/NCT02592551?view=record. Tremelimumab-actl, a cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) blocking human IgG2 monoclonal antibody, is produced by recombinant DNA 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). Infusion-related reactions occurred in 10 (2.6%) patients receiving IMFINZI and IMJUDO. The site is secure. Tremelimumab is a human monoclonal antibody and potential new medicine that targets the activity of cytotoxic T-lymphocyte-associated protein 4 (CTLA-4). 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 WebCleviprex is supplied in sterile, pre-mixed, ready-to-use 50 mL or 100 mL vials. Monitor for signs and symptoms of infusion-related reactions. Initial early phase studies of the drug often showed promising results, in which the drug stopped tumors from growing for periods of time. Request free informational, treatment, financial or support resources to help you and your loved one after a mesothelioma diagnosis. (2016). Withhold or discontinue tremelimumab-actl in combination with durvalumab based on the severity. CTLA-4 is a negative regulator of T-cell activity. Eight patients (8/29) required other immunosuppressants. Tremelimumab-actl can cause fetal harm when administered to a pregnant woman. The Mesothelioma Center at Asbestos.com has provided patients and their loved ones the most updated and reliable information on mesothelioma and asbestos exposure since 2006. In cases of corticosteroid-refractory colitis, consider repeating infectious workup to exclude alternative etiologies. Based on findings from animal studies and its mechanism of action, tremelimumab-actl can cause fetal harm when administered to a pregnant woman. It is used with Immune-mediated adverse reactions listed herein may not be inclusive of all possible severe and fatal immune-mediated reactions. She graduated with a Bachelor of Arts degree from the University of Illinois at Chicago, where she majored in communication and minored in sociology. AHFSfirstRelease. Specialists suggest that both medications in combination may interfere with the ability of malignant tumor cells to grow and spread. Immune-mediated thyroiditis occurred in 1.2% (7/596) of patients receiving IMFINZI in combination with IMJUDO and platinum-based chemotherapy. (2019). Immune-mediated thyroiditis occurred in 1.5% (6/388) of patients receiving IMFINZI and IMJUDO. Tremelimumab AstraZeneca will be available as a 20 mg/ml concentrate for solution for infusion. For more information, visit our sponsor page. Tremelimumab has produced promising anticancer responses in early clinical trials. Clinical Trials Using Tremelimumab. Retrieved from, Calabro, L. et al. Resources for Information | Approved Drugs, Recalls, Market Withdrawals and Safety Alerts, Resources for Information | Approved Drugs, Oncology (Cancer) / Hematologic Malignancies Approval Notifications, Verified Clinical Benefit | Cancer Accelerated Approvals, Approved Drug Products with Therapeutic Equivalence Evaluations (Orange Book) Short Description, FDA approves tremelimumab in combination with durvalumab for unresectable hepatocellular carcinoma, View full prescribing information for Imjudo, NCI: Coronavirus: What People WithCancer Should Know. Definition of tremelimumab. Initiate hormone replacement therapy for hypothyroidism or institute medical management of hyperthyroidism as clinically indicated. A Study of Tremelimumab Combined With the Anti-PD-L1 MEDI4736 Antibody in Malignant Mesothelioma (NIBIT-MESO-1). Three patients also required endocrine therapy. Read more about the latest news and research on mesothelioma, asbestos regulations, and emerging treatments. Immune-mediated rash or dermatitis occurred in 4.9% (19/388) of patients receiving IMFINZI and IMJUDO, including Grade 4 (0.3%) and Grade 3 (1.5%) adverse reactions. Download our guide to get the latest information about mesothelioma treatments, clinical trials, complementary and emerging therapies. For Grade 1 or 2 infusion-related reactions, consider using pre-medications with subsequent doses. 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. Events resolved in 2 of the 6 patients. In 2017, mesothelioma survivor and Navy veteran Jim McWhorter joined a clinical trial testing tremelimumab and durvalumab, another immunotherapy drug. 0 This website and its content may be deemed attorney advertising. Based on their mechanism of action and data from animal studies, IMFINZI and IMJUDO can cause fetal harm when administered to a pregnant woman. hbbd```b``y"3@$>K mX d g0"Y$C,@m!X2ZqX%(9JR;BI:@ s Body weight less than 30 kg: tremelimumab-actl 4 mg/kg as a single dose in combination with durvalumab 20 mg/kg at Cycle 1/Day 1, followed by durvalumab 20 mg/kg as a single agent every 4 weeks. It might be most effective when combined with other immunotherapy drugs. The most common Grade 3 or 4 adverse reactions (3%) were pneumonia (7%) and pneumonitis/radiation pneumonitis (3.4%), In patients with Stage III NSCLC in the PACIFIC study receiving IMFINZI (n=475), discontinuation due to adverse reactions occurred in 15% of patients in the IMFINZI arm. Stay up-to-date on treatment, research, clinical trials, doctors and survivors. Tremelimumab. No overall differences in safety or efficacy of tremelimumab-actl have been observed between patients 65 years or older and younger adult patients. In patients who did not receive recent prior radiation, the incidence of immune-mediated pneumonitis was 2.4% (34/1414), including fatal (<0.1%), and Grade 3-4 (0.4%) adverse reactions. Exfoliative dermatitis, including Stevens Johnson Syndrome (SJS), drug rash with eosinophilia and systemic symptoms (DRESS), and toxic epidermal necrolysis (TEN), has occurred with CTLA-4 and PD-1/L-1 blocking antibodies. Clinical trials of tremelimumab have shown it may help control several different types of cancer including lung cancer and mesothelioma. Other immune-mediated adverse reactions: Advise patients to contact their healthcare provider immediately for signs or symptoms of aseptic meningitis, immune thrombocytopenia, myocarditis, hemolytic anemia, myositis, uveitis, keratitis, and myasthenia gravis. In combination with durvalumab, a PD-L1 inhibitor, these drugs have the potential for induction of immune-mediated adverse reactions. 2023 AstraZeneca. If uveitis occurs in combination with other immune-mediated adverse reactions, consider a Vogt-Koyanagi-Harada-like syndrome, as this may require treatment with systemic steroids to reduce the risk of permanent vision loss. Registered oncology nurse with more than 30 years experience, Expertise in mesothelioma, health effects of asbestos, cancer therapy and immunotherapy, Assisted surgeons with lung resections, lung transplants and pneumonectomies, Ran tissue procurement program at the University of Florida, Calabro, L. et al. MEDI4736 Or MEDI4736 + Tremelimumab In Surgically Resectable Malignant Pleural Mesothelioma. For additional information until a more detailed monograph is developed and published, the manufacturer's labeling should be consulted. (n.d.). Upon improvement to Grade 1 or less, initiate corticosteroid taper and continue to taper over at least 1 month. Events resolved in 15 of the 18 patients. Endocrinopathies: Advise patients to contact their healthcare provider immediately for signs or symptoms of hypothyroidism, hyperthyroidism, adrenal insufficiency, type 1 diabetes mellitus, or hypophysitis. If you are looking for mesothelioma support, please contact our Patient Advocates at (855) 404-4592. Results from a recent study at Rice University in Houston are exciting. This material is provided for educational purposes only and is not intended for medical advice, diagnosis or treatment. Serious adverse reactions occurred in 47% of patients receiving IMFINZI plus chemotherapy. Withhold or permanently discontinue tremelimumab-actl and durvalumab depending on severity. Immune-mediated colitis occurred in 6.5% (39/596) of patients receiving IMFINZI in combination with IMJUDO and platinum-based chemotherapy including fatal (0.2%) and Grade 3 (2.5%) adverse reactions. Written by Their combined expertise means we help any mesothelioma patient or loved one through every step of their cancer journey. Tremelimumab-actl is approved to treat adults with: Hepatocellular carcinoma (a type of liver cancer) that cannot be removed by surgery. Tremelimumab is a human antibody that helps the immune system fight cancer. 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. Three patients also received other immunosuppressants. Cardiac/vascular: Myocarditis, pericarditis, vasculitis. The most frequent serious adverse reactions reported in at least 2% of patients were cholangitis (7%), pyrexia (3.8%), anemia (3.6%), sepsis (3.3%) and acute kidney injury (2.4%). Tremelimumab-actl injection is used in combination with durvalumab to treat liver cancer that cannot be removed by surgery (unresectable hepatocellular carcinoma or uHCC). Copyright 2023, Selected Revisions November 29, 2022. Each infusion will take approximately 1 hour. Retrieved from, ClinicalTrials.gov. Available for Android and iOS devices. Massard C, Gordon MS, Sharma S, et al. These more serious side effects include holes in the intestines, obstruction of the small intestine, inflammation of the colon and skin ulcers. A study called DETERMINE assesses tremelimumab as a second or third-line treatment for malignant mesothelioma patients who ineligible for tumor-removing surgery in a randomized, double-blind study. Immune-mediated adrenal insufficiency occurred in 1.5% (6/388) of patients receiving IMFINZI and IMJUDO, including Grade 3 (0.3%) adverse reactions. A Phase 2 Study of Durvalumab in Combination With Tremelimumab in Malignant Pleural Mesothelioma. Tremelimumab which has no brand name yet has not been approved by the U.S. Food and Drug Administration (FDA) to treat any cancer or disease. Request a free legal case evaluation today. Any unauthorized or illegal use, copying or dissemination will be prosecuted. Several landmark trials have shown tremelimumab can stop mesothelioma tumors from growing for periods of time. Retrieved from, Maio, M. et al. While immune-mediated adverse reactions usually manifest during treatment, immune-mediated adverse reactions can also manifest after discontinuation of tremelimumab-actl and/or durvalumab. Two patients (2/18) required high-dose corticosteroid treatment (at least 40 mg prednisone or equivalent per day). Serious adverse reactions in >1% of patients included hemorrhage (6%), diarrhea (4%), sepsis (2.1%), pneumonia (2.1%), rash (1.5%), vomiting (1.3%), acute kidney injury (1.3%), and anemia (1.3%). Because of the potential for serious adverse reactions in the breastfed child, advise women not to breastfeed during treatment with tremelimumab-actl and for 3 months after the last dose. WebTREMFYA is a clear and colorless to light yellow solution that may contain small translucent particles. (2017, December 13). Immune-mediated colitis or diarrhea occurred in 6% (23/388) of patients receiving IMFINZI and IMJUDO, including Grade 3 (3.6%) adverse reactions. Maternal IgG is known to be present in human milk. All rights reserved. Thyroiditis can present with or without endocrinopathy. Please read our privacy policy and disclaimer for more information about our website. Randomized, Double-blind Study Comparing Tremelimumab to Placebo in Subjects With Unresectable Malignant Mesothelioma (Tremelimumab). This study used the drug alone rather than in combination with other drugs. 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). Initial studies of the drug produced impressive results that havent been replicated in larger clinical trials. Advise female patients not to breastfeed while taking tremelimumab-actl and for at least 3 months after the last dose. 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. 5-star reviewed mesothelioma and support organization. In April 2015, tremelimumab received orphan drug designation by the FDA to treat mesothelioma. 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. Immune-mediated nephritis occurred in 0.5% (10/1889) of patients receiving IMFINZI, including Grade 3 (<0.1%) adverse reactions. All patients required other therapy including hormone replacement therapy, thiamazole, carbimazole, propylthiouracil, perchlorate, calcium channel blocker, or beta-blocker. The safety and effectiveness of IMFINZI and IMJUDO have not been established in pediatric patients. al. The incidence of pneumonitis is higher in patients who have received prior thoracic radiation. Human immunoglobulin G2 (IgG2) is known to cross the placental barrier; therefore, tremelimumab-actl has the potential to be transmitted from the mother to the developing fetus. In females of reproductive potential, verify pregnancy status prior to initiating IMFINZI and IMJUDO and advise them to use effective contraception during treatment with IMFINZI and IMJUDO and for 3 months after the last dose of IMFINZI and IMJUDO. hb```e``>' @1V x/6RVj. 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. Institute medical management promptly, including specialty consultation as appropriate. 8 It binds to its target, human CTLA-4, with high selectivity 2 and subnanomolar affinity. Tremelimumab-actl, a cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) blocking antibody, is an antineoplastic agent. There are therapies and medications to treat every side effect. Drug class: anti-CTLA-4 monoclonal antibodies. Advise pregnant women and females of reproductive potential of the potential risk to a fetus. Tremelimumab-actl is a monoclonal antibody that blocks T-cell inhibitory signals induced by the CTLA-4 pathway, thereby removing inhibition of the immune response. Other (hematologic/immune): Hemolytic anemia, aplastic anemia, hemophagocytic lymphohistiocytosis, systemic inflammatory response syndrome, histiocytic necrotizing lymphadenitis (Kikuchi lymphadenitis), sarcoidosis, and immune thrombocytopenia.