tremelimumab package insert tremelimumab package insert

Events resolved in 6 of the 9 patients. WebOn October 21, 2022, the Food and Drug Administration approved tremelimumab (Imjudo, AstraZeneca Pharmaceuticals) in combination with durvalumab for adult patients with Tremelimumab (CP-675,206), a Cytotoxic T LymphocyteAssociated Antigen 4 Blocking Monoclonal Antibody in Clinical Development for Patients with Cancer. CAS number: 745013-59-6. Withhold or discontinue tremelimumab-actl in combination with durvalumab based on the severity. 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. It is used with Both durvalumab and tremelimumab have been tested for mesothelioma alone, but not in combination. Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details. 8 It binds to its target, human CTLA-4, with high selectivity 2 and subnanomolar affinity. A Phase 2 Study of Durvalumab in Combination With Tremelimumab in Malignant Pleural Mesothelioma. Refer to the prescribing information for agents administered in combination with tremelimumab-actl for breastfeeding recommendations, as appropriate. However, combining tremelimumab and durvalumab has proven more effective against lung cancer than tremelimumab alone. Small studies indicate about half of mesothelioma patients respond to tremelimumab and about half live at least one year on the drug. 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). Imjudo (tremelimumab) is a human monoclonal antibody that targets the activity of cytotoxic T-lymphocyte-associated protein 4 (CTLA-4). The purpose of tremelimumab is to blog receptors on immune cells that normally suppress immune attacks. (2019). The information on this website is proprietary and protected. AHFS Drug Information. (n.d.). Retrieved March 4, 2023, from https://www.asbestos.com/treatment/immunotherapy/tremelimumab/. Retrieved from, National Cancer Institute. In addition to being investigated as a monotherapy treatment for patients with mesothelioma, tremelimumab is currently being studied in combination with 5 WARNINGS AND PRECAUTIONS No overall differences in safety or efficacy of tremelimumab-actl have been observed between patients 65 years or older and younger adult patients. MEDI4736 Or MEDI4736 + Tremelimumab In Surgically Resectable Malignant Pleural Mesothelioma. Tremelimumab. Journal of Clinical Oncology,34, No. (n.d.). IMFINZI and IMJUDO can cause immune-mediated colitis that is frequently associated with diarrhea. Infusion-related reactions occurred in 2.2% (42/1889) of patients receiving IMFINZI, including Grade 3 (0.3%) adverse reactions. The site is secure. 465 0 obj <>stream For Grade 1 or 2 infusion-related reactions, consider using pre-medications with subsequent doses. Please see Full Prescribing Information including Medication Guide for IMFINZI and IMJUDO. Systemic corticosteroids were required in all 29 patients and all 29 patients required high-dose corticosteroid treatment (at least 40 mg prednisone or equivalent per day). Immune-mediated hypothyroidism occurred in 11% (42/388) of patients receiving IMFINZI and IMJUDO. IMFINZI in combination with IMJUDO is indicated for the treatment of adult patients with unresectable hepatocellular carcinoma (uHCC). Clinical trials began testing tremelimumab on mesothelioma in 2013. 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. Tremelimumab is given by intravenous infusion every 4 weeks for a maximum of 4 doses over 16 weeks. Other Immune-Mediated Pancreatitis: Tremelimumab-actl in combination with durvalumab can cause immune-mediated pancreatitis. The results led the researchers to conclude that the treatment combination was associated with long-term survival. Imjudo blocks the The study concluded is estimated to be completed in late 2019. Medically reviewed by Drugs.com on Nov 29, 2022. Immune-mediated colitis occurred in 2% (37/1889) of patients receiving IMFINZI, including Grade 4 (<0.1%) and Grade 3 (0.4%) adverse reactions. The drug usually stops cancer growth for several months before it stops working altogether, a reason why it hasnt been FDA approved to treat mesothelioma. Consider administration of other systemic immunosuppressants in patients whose immune-mediated adverse reactions are not controlled with corticosteroid therapy. The medication was first studied as a treatment for metastatic melanoma. In animal studies, CTLA-4 blockade is associated with higher incidence of pregnancy loss. Dosage summary: Administer tremelimumab-actl as an intravenous infusion over 60 minutes after dilution. IMFINZI and IMJUDO are registered trademarks and AstraZeneca Access 360 is a trademark of the AstraZeneca group of companies. A Phase 2 Study of Durvalumab in Combination With Tremelimumab in Malignant Pleural Mesothelioma. Advise females of reproductive potential to use effective contraception during treatment and for at least 3 months after the last dose of tremelimumab-actl. 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. While smaller trials have shown success, more research on the drug is needed to treat future patients. 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. Systemic corticosteroids were required in all patients with immune-mediated pancreatitis, of these 7 patients required high-dose corticosteroid treatment (at least 40 mg prednisone or equivalent per day). WebUse in Cancer. Most common adverse reactions ( 20%) of patients with uHCC receiving tremelimumab-actl are rash, diarrhea, fatigue, pruritus, musculoskeletal pain, and abdominal pain. 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. Initial early phase studies of the drug often showed promising results, in which the drug stopped tumors from growing for periods of time. Retrieved from, ClinicalTrials.gov. Tremelimumab-actl is indicated, in combination with durvalumab, for the treatment of adult patients with unresectable hepatocellular carcinoma (uHCC). CTLA-4 plays a role in maintaining maternal immune tolerance to the fetus to preserve pregnancy and in immune regulation of the newborn. Asbestos.com, 24 Feb 2023, https://www.asbestos.com/treatment/immunotherapy/tremelimumab/. Tremelimumab is considered an immune checkpoint blocker because it blocks a protein called CTLA-4, which deactivates killer T cells. Medications like tremelimumab are designed to fight cancer cells by increasing the amount of activated killer T cells. Retrieved from, Guazzelli, A. Clinical trials of tremelimumab have shown it may help control several different types of cancer including lung cancer and mesothelioma. Immune-mediated Thyroiditis: Immune-mediated thyroiditis occurred in 1.5% (6/388) of patients receiving tremelimumab-actl in combination with durvalumab. Immune-mediated adrenal insufficiency occurred in 0.5% (9/1889) of patients receiving IMFINZI, including Grade 3 (<0.1%) adverse reactions. The active substance of Tremelimumab AstraZeneca is tremelimumab, a monoclonal antibody ( ATC code: L01FX20). Dont try to tough it out, even with mild side effects. 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. 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. 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. Nerve inflammation (peripheral neuropathy), Renowned mesothelioma center Dana-Farber Cancer Institute in 2017 opened a phase II trial. Eventually, the cancer returned and McWhorter had to leave that trial in search of other options to control his cancer. Available for Android and iOS devices. 2. Withhold or permanently discontinue tremelimumab-actl and durvalumab depending on severity. Massard C, Gordon MS, Sharma S, et al. Nearly 37 percent of participants survived at least two years in one of the studies. Clinical trials on tremelimumab have been conducted on cancer patients in an attempt to study the prevention, detection, or treatment of multiple diseases. Clinical trials often combine the medication with another immunotherapy drug called durvalumab. 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. Around half of the patients lived at least a year in both studies. WebCyramza: EPAR Product Information - European Medicines Agency This review used the Assessment Aid, a voluntary submission from the applicant to facilitate the FDAs assessment. 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. About tremelimumab Tremelimumab is a human monoclonal antibody and potential new medicine that targets the activity of cytotoxic T-lymphocyte-associated Tremelimumab-actl is indicated, in combination with durvalumab, for the treatment of adult patients with unresectable hepatocellular carcinoma (uHCC). 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. Advise patients to contact their healthcare provider immediately for signs or symptoms of infusion-related reactions. This optimistic outcome has researchers hopeful for similar results for mesothelioma patients. Intestinal perforation has been observed in other studies of tremelimumab-actl in combination with durvalumab. 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 Based on their mechanism of action and data from animal studies, IMFINZI and IMJUDO can cause fetal harm when administered to a pregnant woman. A Study of Tremelimumab Combined With the Anti-PD-L1 MEDI4736 Antibody in Malignant Mesothelioma (NIBIT-MESO-1). In 2021, a clinical research study followed up with mesothelioma patients four years after they received tremelimumab and durvalumab. Receptors interpret and respond to signals from multiple factors, such as cancerous cells. Early results in the Phase 2b study have suggested that the drug fails to improve lifespan. Tremelimumab-actl injection is used in combination with durvalumab to treat liver cancer that cannot be removed by surgery (unresectable hepatocellular carcinoma or uHCC). We will help you find the best mesothelioma doctor in your area. The incidence of pneumonitis is higher in patients who have received prior thoracic radiation. Immune checkpoint inhibitors in malignant pleural mesothelioma: promises and challenges. 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. 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. 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 Monitor for signs and symptoms of infusion-related reactions. In April 2015, tremelimumab received orphan drug designation by the FDA to treat mesothelioma. 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%). 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. Would you like to speak with a Patient Advocate? 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). One patient (1/5) required other immunosuppressants. Weve gathered all of our resources into one guide with one purpose: helping you navigate mesothelioma. (n.d.). There are therapies and medications to treat every side effect. 1 Tremelimumab caused increased IL-2 production in a dose-dependent manner in ex-vivo blood stimulation assays using peripheral blood Webc. 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. 20% of patients were alive at 36 months, and 15% of patients survived for 48 months or longer. Three patients also required endocrine therapy. Good research has proven it isnt effective enough on its own to use as a single therapy against mesothelioma. Immune-mediated thyroiditis occurred in 0.5% (9/1889) of patients receiving IMFINZI, including Grade 3 (<0.1%) adverse reactions. Retrieved on November 14, 2019, from https://www.cancer.gov/publications/dictionaries/cancer-drug/def/tremelimumab, Ribas, A., et. 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. Research is ongoing to determine which mesothelioma patients may benefit the most from this drug. 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. Interrupt, slow the rate of, or permanently discontinue IMFINZI and IMJUDO based on the severity. 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. 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 full Prescribing Information for preparation and administration instructions and dosage modifications for adverse reactions. (2019). An orphan drug typically treats uncommon illnesses, and cannot make much of a profit. For more information, visit our sponsor page. 301 0 obj <> endobj Clinical Trials Using Tremelimumab. 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. In cases of corticosteroid-refractory colitis, consider repeating infectious workup to exclude alternative etiologies. Immune-mediated thyroiditis occurred in 1.5% (6/388) of patients receiving IMFINZI and IMJUDO. 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. Serious adverse reactions occurred in 29% of patients receiving IMFINZI. 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 pancreatitis occurred in 2.3% (9/388) of patients receiving IMFINZI and IMJUDO, including Grade 4 (0.3%) and Grade 3 (1.5%) adverse reactions. Immune-mediated adrenal insufficiency occurred in 1.5% (6/388) of patients receiving IMFINZI and IMJUDO, including Grade 3 (0.3%) adverse reactions. Similar clinical trials are underway in Italy and in 104 study locations worldwide. An official website of the United States government, : After Cycle 1 of combination therapy, administer durvalumab as a single agent every 4 weeks until disease progression or unacceptable toxicity occurs. Research in mesothelioma patients shows tremelimumab has the potential to cause life-threatening side effects. Follow patients closely for evidence of transplant-related complications and intervene promptly. (2017, December 13). (2015, October 27). 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. Asbestos.com. Immune-mediated rash or dermatitis occurred in 1.8% (34/1889) of patients receiving IMFINZI, including Grade 3 (0.4%) adverse reactions. Refer to the prescribing information for the agents administered in combination with tremelimumab-actl for recommended contraception duration, as appropriate. The trial was suspended in late 2019 after criteria were not met, but doctors and researchers estimate completion in 2024. Institute medical management promptly, including specialty consultation as appropriate. Calling this number connects you with a Patient Advocate at The Mesothelioma Center, the nation's most trusted mesothelioma resource. co-culturing the second population of T cells in the presence of antigen presenting cells that present one or more non-native peptide on a major histocompatibility complex (MHC Wilmington, DE; AstraZeneca Pharmaceuticals LP; November 2022. Receptors interpret and respond to signals from multiple factors, such as cancerous cells. She is a registered nurse with a background in oncology and thoracic surgery and was the regional director of a tissue bank before becoming a Patient Advocate at The Mesothelioma Center. Thyroid Disorders: Tremelimumab-actl in combination with durvalumab can cause immune-mediated thyroid disorders. Tremelimumab was granted orphan drug designation. (2019). For non-prescription products, read the label or package ingredients carefully. 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. 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). Fatal adverse reactions occurred in 4.9% of patients receiving IMFINZI plus chemotherapy, In patients with locally advanced or metastatic BTC in the TOPAZ-1 study receiving IMFINZI (n=338), the most common adverse reactions (occurring in 20% of patients) were fatigue, nausea, constipation, decreased appetite, abdominal pain, rash, and pyrexia, In patients with locally advanced or metastatic BTC in the TOPAZ-1 study receiving IMFINZI (n=338), discontinuation due to adverse reactions occurred in 6% of the patients receiving IMFINZI plus chemotherapy. Advise pregnant women of the potential risk to a fetus. Antibodies are proteins in the immune system that recognize and attack foreign Immune-mediated colitis or diarrhea occurred in 6% (23/388) of patients receiving tremelimumab-actl in combination with durvalumab, including Grade 3 (3.6%) adverse reactions. Support and resources for HCPs and patients. Retrieved from, Pfizer. Tremelimumab is a cytotoxic agent that works to decrease tumour growth. Two patients (0.5%, 2/388) had events of hyperglycemia requiring insulin therapy that had not resolved at last follow-up. The problem is tremelimumab seems to work well for only a little while. 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%). 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. Events resolved in 2 of the 6 patients. et al. She graduated with a Bachelor of Arts degree from the University of Illinois at Chicago, where she majored in communication and minored in sociology. If youre still feeling overwhelmed, let us help you seek the advice you need. Immune-mediated hepatitis occurred in 7.5% (29/388) of patients receiving tremelimumab-actl in combination with durvalumab, including fatal (0.8%), Grade 4 (0.3%), and Grade 3 (4.1%) adverse reactions. "My family has only the highest compliment for the assistance and support that we received from The Mesothelioma Center. 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. Events resolved in 15 of the 18 patients. Topical emollients and/or topical corticosteroids may be adequate to treat mild to moderate non-exfoliative rashes. There are no data on the presence of tremelimumab-actl in human milk, its effects on a breastfed child, or on milk production. Stay up-to-date on treatment, research, clinical trials, doctors and survivors. %PDF-1.7 % Of the patients who received IMFINZI (475), 1.1% were fatal and 2.7% were Grade 3 adverse reactions. Withhold or permanently discontinue IMFINZI and IMJUDO depending on severity. For patients with mesothelioma cancer, immunotherapy is a promising new field. There are no available data on the use of tremelimumab-actl in pregnant women. If receiving both durvalumab and tremelimumab for the first 4 cycles, they will be given on the same day. WebIMJUDO (tremelimumab-actl) injection, for intravenous use Initial U.S. Approval: 2022----- INDICATIONS AND USAGE -----IMJUDOis a cytotoxic T-lymphocyte-associated