Dosage summary: Administer tremelimumab-actl as an intravenous infusion over 60 minutes after dilution. The problem is tremelimumab seems to work well for only a little while. Please see Full Prescribing Information including Medication Guide for IMFINZI and IMJUDO. The tremelimumab antibody activates an immune cell known as cytotoxic T lymphocytes (CTLs), or killer T cells. 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. Efficacy was evaluated in HIMALAYA (NCT03298451), a randomized (1:1:1), open-label, multicenter study in patients with confirmed uHCC who had not received prior systemic treatment for HCC. (n.d.). These complications may occur despite intervening therapy between PD-1/L-1 blockade and allogeneic HSCT. 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 Global Health Status/QoL and Functioning Scales, Adverse Reactions and Discontinuation Rates. An increase in activated killer T cells helps a persons immune system fight cancer. 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). Withhold or permanently discontinue tremelimumab-actl in combination with durvalumab depending on severity Immune-mediated hypophysitis/hypopituitarism occurred in 1.1% (5/462) of patients receiving the STRIDE regimen (combination of tremelimumab-actl with durvalumab). 20% of patients were alive at 36 months, and 15% of patients survived for 48 months or longer. 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. 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. IMFINZI and IMJUDO can cause immune-mediated nephritis. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, Maryland 20814. 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. endstream endobj startxref She graduated with a Bachelor of Arts degree from the University of Illinois at Chicago, where she majored in communication and minored in sociology. 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). (2019). Researchers suggested more trials that combine drugs are necessary to see how well tremelimumab may work against mesothelioma. Small studies indicate about half of mesothelioma patients respond to tremelimumab and about half live at least one year on the drug. Karen Selby, RN Each infusion will take approximately 1 hour. Drug class: anti-CTLA-4 monoclonal antibodies. He initially responded quite well. Tremelimumab (CP-675,206), a Cytotoxic T LymphocyteAssociated Antigen 4 Blocking Monoclonal Antibody in Clinical Development for Patients with Cancer. All rights reserved. Last Modified: September 22, 2022, Created: July 6, 2022. IMFINZI and IMJUDO can cause immune-mediated colitis that is frequently associated with diarrhea. 1 Tremelimumab caused increased IL-2 production in a dose-dependent manner in ex-vivo blood stimulation assays using peripheral blood This study used the drug alone rather than in combination with other drugs. 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. For information on the COVID-19 pandemic, see the following resources: Follow the Oncology Center of Excellence on Twitter@FDAOncology. Written by ASHP. AstraZeneca stopped the trial in 2016 when they realized it was not working well enough. Retrieved March 4, 2023, from https://www.asbestos.com/treatment/immunotherapy/tremelimumab/. Pancreatitis: Advise patients to contact their healthcare provider immediately for signs or symptoms of 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. In her free time, Rachel likes to be outdoors, watch movies, and spend time with her animals. In a murine model of pregnancy, CTLA-4 blockade resulted in increased resorptions and reduced live fetuses. Immune-Mediated Pneumonitis: Tremelimumab-actl in combination with durvalumab can cause immune-mediated pneumonitis, which may be fatal. WebTremelimumab blocks the binding of the antigen-presenting cell ligands B7.1 and B7.2 to CTLA-4, resulting in inhibition of B7-CTLA-4-mediated downregulation of T-cell activation; Request free informational, treatment, financial or support resources to help you and your loved one after a mesothelioma diagnosis. 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. Randomized, Double-blind Study Comparing Tremelimumab to Placebo in Subjects With Unresectable Malignant Mesothelioma (Tremelimumab). View full prescribing information for Imjudo. 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. Immune checkpoint inhibitors in malignant pleural mesothelioma: promises and challenges. The results led the researchers to conclude that the treatment combination was associated with long-term survival. WebIMJUDO (tremelimumab-actl) injection, for intravenous use Initial U.S. Approval: 2022----- INDICATIONS AND USAGE -----IMJUDOis a cytotoxic T-lymphocyte-associated Orphan designation does not mean the drug is safe or effective. Medications like tremelimumab are designed to fight cancer cells by increasing the amount of activated killer T cells. Hepatitis: Advise patients to contact their healthcare provider immediately for jaundice, severe nausea or vomiting, pain on the right side of abdomen, lethargy, or easy bruising or bleeding. IMFINZI and IMJUDO can cause immune-mediated rash or dermatitis. The purpose of tremelimumab is to blog receptors on immune cells that normally suppress immune attacks. Karen Selby joined Asbestos.com in 2009. Immune-mediated hypophysitis/hypopituitarism occurred in 1% (4/388) of patients receiving IMFINZI and IMJUDO. Efficacy and safety of an intensified schedule of tremelimumab for chemotherapy-resistant malignant mesothelioma: an open-label, single-arm, phase 2 study. Retrieved from, ClinicalTrials.gov. AHFSfirstRelease. Interrupt, slow the rate of, or permanently discontinue IMFINZI and IMJUDO based on the severity. Several clinical trials continue to test the drug in mesothelioma patients, including Dr. David Sugarbakers trial that combines tremelimumab with durvalumab and surgery. Topical emollients and/or topical corticosteroids may be adequate to treat mild to moderate non-exfoliative rashes. 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. 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 Nephritis with Renal Dysfunction: Tremelimumab-actl in combination with durvalumab can cause immune-mediated nephritis. Immune-mediated adverse reactions listed herein may not be inclusive of all possible severe and fatal immune-mediated reactions. Prior results do not predict a similar outcome. Systemic corticosteroids were required in all 6 patients and of these, 1 patient required high-dose corticosteroid treatment (at least 40 mg prednisone or equivalent per day). For non-prescription products, read the label or package ingredients carefully. Immune-mediated adverse reactions, which may be severe or fatal, can occur in any organ system or tissue. Our Patient Advocates can help guide you or your loved one through the steps to take after a mesothelioma diagnosis. Other Immune-Mediated Pancreatitis: Tremelimumab-actl in combination with durvalumab can cause immune-mediated pancreatitis. Advise pregnant women and females of reproductive potential of the potential risk to a fetus. Initial early phase studies of the drug often showed promising results, in which the drug stopped tumors from growing for periods of time. Several landmark trials have shown tremelimumab can stop mesothelioma tumors from growing for periods of time. Lancet Respir Med, 3(4), 301-309. doi: 10.1016/S2213-2600(15)00092-2, Ceresoli, G.L., Bonomi, M., & Sauta, M.G. Tremelimumab. Immune-mediated Hyperthyroidism: Immune-mediated hyperthyroidism occurred in 4.6% (18/388) of patients receiving tremelimumab-actl in combination with durvalumab, including Grade 3 (0.3%) adverse reactions. Tremelimumab plus durvalumab retreatment and 4-year outcomes in patients with mesothelioma: a follow-up of the open label, non-randomised, phase 2 NIBIT-MESO-1 study. Thyroiditis can present with or without endocrinopathy. Imjudo blocks the If receiving both durvalumab and tremelimumab for the first 4 cycles, they will be given on the same day. 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. There are therapies and medications to treat every side effect. 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%). Immune-mediated thyroiditis occurred in 0.5% (9/1889) of patients receiving IMFINZI, including Grade 3 (<0.1%) adverse reactions. See USPI Dosing and Administration for specific details. Immune-mediated nephritis occurred in 0.5% (10/1889) of patients receiving IMFINZI, including Grade 3 (<0.1%) adverse reactions. WebTremelimumab is an investigational, fully human IgG monoclonal antibody directed against CTLA-4, a coinhibitory receptor that represses effector T-cell activity in cancer. Helps more than 50% of mesothelioma patients diagnosed annually in the U.S. A+ rating from the Better Business Bureau. Severe and Fatal Immune-Mediated Adverse Reactions Advise female patients not to breastfeed while taking tremelimumab-actl and for at least 3 months after the last dose. In cases of corticosteroid-refractory colitis, consider repeating infectious workup to exclude alternative etiologies. Research in mesothelioma patients shows tremelimumab has the potential to cause life-threatening side effects. Tremelimumab is a human monoclonal antibody and potential new medicine that targets the activity of cytotoxic T-lymphocyte-associated protein 4 (CTLA-4). However, a phase III trial of tremelimumab mo Since then, multiple studies have tested the drug on several types of cancer. Tremelimumab granted Orphan Drug Designation by US FDA for treatment of malignant mesothelioma. 5 WARNINGS AND PRECAUTIONS For Grade 1 or 2 infusion-related reactions, consider using pre-medications with subsequent doses. There are no data on the presence of tremelimumab-actl in human milk, its effects on a breastfed child, or on milk production. For additional information until a more detailed monograph is developed and published, the manufacturer's labeling should be consulted. 465 0 obj <>stream Borrie, A., & Vareki, M. (2018). Seventeen patients required other therapy (thiamazole, carbimazole, propylthiouracil, perchlorate, calcium channel blocker, or beta-blocker). Retrieved on November 14, 2019, from https://www.sciencedirect.com/topics/neuroscience/tremelimumab, Mayo Clinic. Tremelimumab-actl is available in the following dosage form(s) and strength(s): Injection: 25 mg/1.25 mL (20 mg/mL) solution in "Tremelimumab." 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. These include ischemic or hemorrhagic stroke (4 patients), sepsis (2 patients), and upper gastrointestinal hemorrhage (2 patients), In patients with unresectable HCC in the HIMALAYA study receiving IMFINZI and IMJUDO, the most common adverse reactions (occurring in 20% of patients) were rash, diarrhea, fatigue, pruritus, musculoskeletal pain, and abdominal pain, In patients with unresectable HCC in the HIMALAYA study receiving IMFINZI and IMJUDO, serious adverse reactions occurred in 41% of patients. 2023 AstraZeneca. by Asbestos.com and The Mesothelioma Center. 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. Various grades of visual impairment to include blindness can occur. Inform patients of the risk of immune-mediated adverse reactions that may require corticosteroid treatment and interruption or discontinuation of tremelimumab-actl in combination with durvalumab. Mated genetically engineered mice heterozygous for CTLA-4 (CTLA-4+/-) gave birth to CTLA-4+/- offspring and offspring deficient in CTLA-4 (homozygous negative, CTLA-4-/-) that appeared healthy at birth. Asbestos.com. Early identification and management of immune-mediated adverse reactions are essential to ensure safe use of tremelimumab-actl in combination with durvalumab. Once an antibody attaches to an antigen on a molecule, receptors signal the immune system to fight back. A Study of Tremelimumab Combined With the Anti-PD-L1 MEDI4736 Antibody in Malignant Mesothelioma (NIBIT-MESO-1). Intestinal perforation has been observed in other studies of tremelimumab-actl in combination with durvalumab. Drug class: Antineoplastic Agents Positive results from the HIMALAYA Phase III trial showed a single priming dose of tremelimumab added to Imfinzi (durvalumab) demonstrated a statistically significant and clinically meaningful improvement in overall survival (OS) versus sorafenib as a 1st-line treatment for patients with unresectable hepatocellular carcinoma (HCC) who had not Systemic corticosteroids were required in all patients, of these 4 patients required high-dose corticosteroid treatment (at least 40 mg prednisone or equivalent per day). 2. Maternal IgG is known to be present in human milk. "My family has only the highest compliment for the assistance and support that we received from The Mesothelioma Center. Tremelimumab-actl, a cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) blocking antibody, is an antineoplastic agent. 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. Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations. New clinical trials are testing it in combination with several anti-cancer drugs with the hope of finding a magic combination. (2016). The CTLA-4-/- homozygous negative offspring developed signs of a lymphoproliferative disorder and died by 3 to 4 weeks of age with multiorgan tissue destruction. For assistance with single-patient INDs for investigational oncology products, healthcare professionals may contact OCEs Project Facilitate at 240-402-0004 or email [email protected]. Retrieved from, Calabro, L. et al. 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. Their combined expertise means we help any mesothelioma patient or loved one through every step of their cancer journey. Receptors interpret and respond to signals from multiple factors, such as cancerous cells. This website and its content may be deemed attorney advertising. Tremelimumab as second-line or third-line treatment in relapsed malignant mesothelioma (DETERMINE): a multicentre, international, randomised, double-blind, placebo-controlled phase 2b trial. Interrupt, slow the rate of, or permanently discontinue tremelimumab-actl and durvalumab based on the severity. Withhold or permanently discontinue tremelimumab-actl in combination with durvalumab based on the severity Immune-mediated adrenal insufficiency occurred in 1.5% (6/388) of patients receiving tremelimumab-actl in combination with durvalumab, including Grade 3 (0.3%) adverse reactions. Serious adverse reactions occurred in 29% of patients receiving IMFINZI. Tremelimumab is a cancer treatment drug manufactured by AstraZeneca. See USPI Dosing and Administration for specific details. See full Prescribing Information for preparation and administration instructions and dosage modifications for adverse reactions. Researchers estimate the study will be completed in late 2019. Material safety data sheet: Tremelimumab. Monitor for signs and symptoms of infusion-related reactions. Topical emollients and/or topical corticosteroids may be adequate to treat mild to moderate non-exfoliative rashes. Lancet, 18(9), 1261-1273. doi: 10.1016/S1470-2045(17)30446-1, Kindler, H.L. 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.