tremelimumab package insert

IMJUDO (tremelimumab) in combination with IMFINZI Cytomegalovirus (CMV) infection/reactivation has been reported in patients with corticosteroid-refractory immune-mediated colitis. Available for Android and iOS devices. Tremelimumab granted Orphan Drug Designation by US FDA for treatment of malignant mesothelioma. Immune-mediated pneumonitis occurred in 3.5% (21/596) of patients receiving IMFINZI in combination with IMJUDO and platinum-based chemotherapy, including fatal (0.5%), and Grade 3 (1%) adverse reactions. Written by Would you like to speak with a Patient Advocate? AHFSfirstRelease. This optimistic outcome has researchers hopeful for similar results for mesothelioma patients. Retrieved on November 14, 2019, from http://theoncologist.alphamedpress.org/content/12/7/873.full, United States National Library of Medicine. IMJUDO (tremelimumab) in combination with IMFINZI (durvalumab) approved in the US for patients with unresectable liver cancer PUBLISHED 24 October In general, if combination of tremelimumab-actl and durvalumab requires interruption or discontinuation, administer systemic corticosteroid therapy (1 to 2 mg/kg/day prednisone or equivalent) until improvement to Grade 1 or less. 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 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. IMFINZI, in combination with IMJUDO and platinum-based chemotherapy, is indicated for the treatment of adult patients with metastatic NSCLC with no sensitizing epidermal growth factor receptor (EGFR) mutations or anaplastic lymphoma kinase (ALK) genomic tumor aberrations. By blocking CTLA-4, tremelimumab activates killer T cells so they can get to work fighting cancer. WebOn October 21, 2022, the Food and Drug Administration approved tremelimumab (Imjudo, AstraZeneca Pharmaceuticals) in combination with durvalumab for adult patients with dyes, preservatives, or animals. Tremelimumab blocks the activity of CTLA-4, contributing to T-cell activation, priming the immune response to cancer and fostering cancer cell death. Would you like to speak with a Patient Advocate? Similar clinical trials are underway in Italy and in 104 study locations worldwide. Tremelimumab is a human monoclonal antibody and potential new medicine that targets the activity of cytotoxic T-lymphocyte-associated protein 4 (CTLA-4). IMFINZI in combination with IMJUDO is indicated for the treatment of adult patients with unresectable hepatocellular carcinoma (uHCC). After Cycle 1 of combination therapy, administer durvalumab as a single agent every 4 weeks until disease progression or unacceptable toxicity occurs. Connect with mesothelioma patients around the country who are battling the disease. Various grades of visual impairment to include blindness can occur. Please see Full Prescribing Information including Medication Guide for IMFINZI and IMJUDO. The effects of local gastrointestinal exposure and limited systemic exposure in the breastfed child to tremelimumab-actl are unknown. %%EOF Access free resources to help you or a loved one after a mesothelioma diagnosis. Tremelimumab as second- or third-line treatment of unresectable malignant mesothelioma (MM): Results from the global, double-blind, placebo-controlled DETERMINE study. Request free informational, treatment, financial or support resources to help you and your loved one after a mesothelioma diagnosis. Institute medical management promptly, including specialty consultation as appropriate. 465 0 obj <>stream IMFINZI and IMJUDO can cause immune-mediated rash or dermatitis. Tremelimumab-actl is available in the following dosage form(s) and strength(s): Injection: 25 mg/1.25 mL (20 mg/mL) solution in a single-dose vial. Previous studies have shown both mild and serious side effects in mesothelioma patients who receive tremelimumab as treatment. 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%). Early results in the Phase 2b study have suggested that the drug fails to improve lifespan. This Fatal pneumonitis or radiation pneumonitis and fatal pneumonia occurred in <2% of patients and were similar across arms, In patients with mNSCLC in the POSEIDON study receiving IMFINZI and IMJUDO plus platinum-based chemotherapy (n=330), the most common adverse reactions (occurring in 20% of patients) were nausea (42%), fatigue (36%), musculoskeletal pain (29%), decreased appetite (28%), rash (27%), and diarrhea (22%), In patients with mNSCLC in the POSEIDON study receiving IMFINZI in combination with IMJUDO and platinum-based chemotherapy (n=330), permanent discontinuation of IMFINZI or IMJUDO due to an adverse reaction occurred in 17% of patients. Tremelimumab | Has The FDA Approved It? - asbestos Drug class: anti-CTLA-4 monoclonal antibodies. The active substance of Tremelimumab AstraZeneca is tremelimumab, a monoclonal antibody ( ATC code: L01FX20). (n.d.). Medications like tremelimumab are designed to fight cancer cells by increasing the amount of activated killer T cells. Refer to the prescribing information for the agents administered in combination with tremelimumab-actl for recommended contraception duration, as appropriate. Immune-mediated colitis or diarrhea occurred in 6% (23/388) of patients receiving IMFINZI and IMJUDO, including Grade 3 (3.6%) adverse reactions. and tremelimumab with chemotherapy demonstrated overall Dermatological reactions: Advise patients to contact their healthcare provider immediately for signs or symptoms of severe dermatological reactions. Tremelimumab has been tested on a variety of cancers including mesothelioma, lung cancer, melanoma, liver cancer, bladder cancer and head and neck cancer. Advise females of reproductive potential to use effective contraception during treatment and for at least 3 months after the last dose of tremelimumab-actl. This review used the Assessment Aid, a voluntary submission from the applicant to facilitate the FDAs assessment. Tremelimumab - Wikipedia Withhold or permanently discontinue tremelimumab-actl in combination with durvalumab depending on severity. Calling this number connects you with a Patient Advocate at The Mesothelioma Center, the nation's most trusted mesothelioma resource. CONTRAINDICATIONS . Immune-mediated hypothyroidism occurred in 11% (42/388) of patients receiving IMFINZI and IMJUDO. 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). See USPI Dosing and Administration for specific details. Other Immune-Mediated Pancreatitis: Tremelimumab-actl in combination with durvalumab can cause immune-mediated pancreatitis. 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. Immune-mediated hyperthyroidism occurred in 2.1% (39/1889) of patients receiving IMFINZI. US-63354; US-65135; US-65136; US-71396 Last Updated 1/23, WITH IMFINZI ALONE OR IN COMBINATION WITH IMJUDO, IMFINZI with IMJUDO and Platinum-Based Chemotherapy, Thyroid Disorders (Thyroiditis, Hyperthyroidism, and Hypothyroidism), Type 1 Diabetes Mellitus, which can present with diabetic ketoacidosis, Musculoskeletal and connective tissue disorders. Tremelimumab as second-line or third-line treatment in relapsed malignant mesothelioma (DETERMINE): a multicentre, international, randomised, double-blind, placebo-controlled phase 2b trial. You may report side effects related to AstraZeneca products by clicking here. (2019). Upon improvement to Grade 1 or less, initiate corticosteroid taper and continue to taper over at least 1 month. 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). et al. 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. %PDF-1.7 % 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 Tremelimumab is a cancer treatment drug manufactured by AstraZeneca. IMFINZI (durvalumab) & IMJUDO (tremelimumab-actl) Dosing Pneumonitis: Advise patients to contact their healthcare provider immediately for any new or worsening cough, chest pain, or shortness of breath. It is used with 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. Weve gathered all of our resources into one guide with one purpose: helping you navigate mesothelioma. Cleviprex Full Prescribing Information - Chiesi USA 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. Type 1 Diabetes Mellitus: Monitor patients for hyperglycemia or other signs and symptoms of diabetes. IMFINZI is indicated for the treatment of adult patients with unresectable Stage III non-small cell lung cancer (NSCLC) whose disease has not. Each page includes all sources for full transparency. 20% of patients were alive at 36 months, and 15% of patients survived for 48 months or longer. Two patients (2/18) required high-dose corticosteroid treatment (at least 40 mg prednisone or equivalent per day). Randomized, Double-blind Study Comparing Tremelimumab to Placebo in Subjects With Unresectable Malignant Mesothelioma (Tremelimumab). Written by ASHP. The most common Grade 3 or 4 adverse reaction (3%) was fatigue/asthenia (3.4%), In patients with extensive-stage SCLC in the CASPIAN study receiving IMFINZI plus chemotherapy (n=265), IMFINZI was discontinued due to adverse reactions in 7% of the patients receiving IMFINZI plus chemotherapy. 8 It binds to its target, human CTLA-4, with high selectivity 2 and subnanomolar affinity. Nervous system: Meningitis, encephalitis, myelitis and demyelination, myasthenic syndrome/myasthenia gravis (including exacerbation), Guillain-Barr syndrome, nerve paresis, autoimmune neuropathy. "Tremelimumab." "My family has only the highest compliment for the assistance and support that we received from The Mesothelioma Center. Cytomegalovirus (CMV) infection/reactivation has been reported in patients with corticosteroid-refractory immune-mediated colitis. WebUse in Cancer. 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. Retrieved from, ClinicalTrials.gov. Withhold or permanently discontinue tremelimumab-actl in combination with durvalumab based on the severity. (2015). Results from a recent study at Rice University in Houston are exciting. Hypophysitis can present with acute symptoms associated with mass effect such as headache, photophobia, or visual field cuts. Tremelimumab-actl, a cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) blocking antibody, is an antineoplastic agent. Asbestos.com. Clinical trials on tremelimumab have been conducted on cancer patients in an attempt to study the prevention, detection, or treatment of multiple diseases. 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. This approval is based on a comparison of the 782 patients randomized to tremelimumab plus durvalumab to sorafenib. In synergistic mouse tumor models, blocking CTLA-4 activity resulted in decreased tumor growth and increased proliferation of T cells in tumors. WebThe STRIDE Regimen (Single Tremelimumab Regular Interval Durvalumab): A single priming dose of IMJUDO 300 mg followed by IMFINZI 1500 mg on Day 1 of Cycle 1; Their combined expertise means we help any mesothelioma patient or loved one through every step of their cancer journey. Cyramza: EPAR Product Information - European Medicines Agency For more information, visit our sponsor page. Advise pregnant women and females of reproductive potential of the potential risk to a fetus. For more information about any of the below clinical trials, they can be found at ClinicalTrials.gov. Tremelimumab We will help you find the best mesothelioma doctor in your area. It binds to CTLA-4, which is primarily expressed on the surface of T lymphocytes, and thus enhances T-cell activation Musculoskeletal and connective tissue disorders: Myositis/polymyositis, rhabdomyolysis and associated sequelae including renal failure, arthritis, polymyalgia rheumatica. Additional efficacy outcomes included investigator-assessed progression-free survival (PFS) and overall response rate (ORR) according to RECIST v1.1. Immune-mediated pancreatitis occurred in 2.3% (9/388) of patients receiving tremelimumab-actl in combination with durvalumab, including Grade 4 (0.3%) and Grade 3 (1.5%) adverse reactions. Since then, multiple studies have tested the drug on several types of cancer. Edited By Walter Pacheco 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 Update your browser for more security, speed and compatibility. Hypophysitis can cause hypopituitarism. Wilmington, DE; AstraZeneca Pharmaceuticals LP; November 2022. Retrieved March 4, 2023, from https://www.asbestos.com/treatment/immunotherapy/tremelimumab/. 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. The problem is tremelimumab seems to work well for only a little while. Immune-mediated hyperthyroidism occurred in 4.6% (18/388) of patients receiving IMFINZI and IMJUDO, including Grade 3 (0.3%) adverse reactions. Evaluate clinical chemistries including liver enzymes, creatinine, adrenocorticotropic hormone (ACTH) level, and thyroid function at baseline and before each dose. Immune-mediated nephritis occurred in 0.7% (4/596) of patients receiving IMFINZI in combination with IMJUDO and platinum-based chemotherapy, including Grade 3 (0.2%) adverse reactions. Two patients (0.5%, 2/388) had events of hyperglycemia requiring insulin therapy that had not resolved at last follow-up. All patients required other therapy (thiamazole, carbimazole, propylthiouracil, perchlorate, calcium channel blocker, or beta-blocker). 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). Lancet, 18(9), 1261-1273. doi: 10.1016/S1470-2045(17)30446-1, Kindler, H.L. Tremelimumab-actl injection is used in combination with durvalumab to treat liver cancer that cannot be removed by surgery (unresectable hepatocellular carcinoma or uHCC). Tremelimumab has produced promising anticancer responses in early clinical trials. Serious adverse reactions occurred in 47% of patients receiving IMFINZI plus chemotherapy. For additional information until a more detailed monograph is developed and published, the manufacturer's labeling should be consulted. 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 Cardiac/vascular: Myocarditis, pericarditis, vasculitis. Dont try to tough it out, even with mild side effects. The purpose of tremelimumab is to blog receptors on immune cells that normally suppress immune attacks. 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. Randomized, Double-blind Study Comparing Tremelimumab to Placebo in Subjects With Unresectable Malignant Mesothelioma (Tremelimumab). An orphan drug typically treats uncommon illnesses, and cannot make much of a profit. Grade 3 immune-mediated Type 1 diabetes mellitus occurred in <0.1% (1/1889) of patients receiving IMFINZI. Immune-mediated hepatitis occurred in 7.5% (29/388) of patients receiving IMFINZI and IMJUDO, including fatal (0.8%), Grade 4 (0.3%) and Grade 3 (4.1%) adverse reactions. 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. The .gov means its official.Federal government websites often end in .gov or .mil. 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%). Reach out any time! 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%). These immune cells kill cancer cells. IMFINZI and IMJUDO can cause severe or life-threatening infusion-related reactions. Events resolved in 3 of the 4 patients and resulted in permanent discontinuation in 2 patients. People see immunotherapy as a more natural approach to fighting cancer because it activates the immune system, but this does not mean serious side effects arent a possibility. The most common (20%) adverse reactions occurring in patients were rash, diarrhea, fatigue, pruritis, musculoskeletal pain and abdominal pain. Immune-mediated Hypothyroidism: Immune-mediated hypothyroidism occurred in 11% (42/388) of patients receiving tremelimumab-actl in combination with durvalumab. Your web browser is no longer supported by Microsoft. Selby, Karen. Imjudo (tremelimumab) is a human monoclonal antibody that targets the activity of cytotoxic T-lymphocyte-associated protein 4 (CTLA-4). Tremelimumab, manufactured by AstraZeneca, is an immunotherapy treatment that helps the immune system recognize and attack cancer cells. Immune-mediated pancreatitis occurred in 1.9% (9/462) of patients receiving the STRIDE regimen (combination of tremelimumab-actl with durvalumab), including Grade 4 (0.2%) and Grade 3 (1.3%) adverse reactions. 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. Most common laboratory abnormalities ( 40%) of patients with uHCC receiving tremelimumab-actl are increased AST, increased ALT, decreased hemoglobin, decreased sodium, increased bilirubin, increased alkaline phosphatase, and decreased lymphocytes. Researchers estimate the study will be completed in late 2019. This website and its content may be deemed attorney advertising. Further research has been done to test the drug as a treatment for metastatic renal cell carcinoma, malignant pleural mesothelioma, metastatic colorectal cancer, and advanced gastric and esophageal adenocarcinoma. If youre still feeling overwhelmed, let us help you seek the advice you need. Monitor for signs and symptoms that may be clinical manifestations of underlying immune-mediated adverse reactions. These complications may occur despite intervening therapy between PD-1/L-1 blockade and allogeneic HSCT. Webc. 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. 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. In patients who received recent prior radiation, the incidence of pneumonitis (including radiation pneumonitis) in patients with unresectable Stage III NSCLC following definitive chemoradiation within 42 days prior to initiation of IMFINZI in PACIFIC was 18.3% (87/475) in patients receiving IMFINZI and 12.8% (30/234) in patients receiving placebo. For information on the COVID-19 pandemic, see the following resources: Follow the Oncology Center of Excellence on Twitter@FDAOncology. 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; 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). Stay up-to-date on treatment, research, clinical trials, doctors and survivors. For patients with mesothelioma cancer, immunotherapy is a promising new field. Study participants with malignant pleural mesothelioma either received MEDI4736, known as durvalumab, or durvalumab and tremelimumab in this phase 2 trial. Severe and Fatal Immune-Mediated Adverse Reactions These more serious side effects include holes in the intestines, obstruction of the small intestine, inflammation of the colon and skin ulcers. Immune-Mediated Colitis: Tremelimumab-actl in combination with durvalumab can cause immune-mediated colitis that is frequently associated with diarrhea. The side effects range from mild to severe. Our fact-checking process begins with a thorough review of all sources to ensure they are high quality. Pancreatitis: Advise patients to contact their healthcare provider immediately for signs or symptoms of pancreatitis. In animal studies, CTLA-4 blockade is associated with higher incidence of pregnancy loss. Our pipeline. The study concluded is estimated to be completed in late 2019. by Asbestos.com and The Mesothelioma Center.