This review used the Assessment Aid, a voluntary submission from the applicant to facilitate the FDAs assessment. 465 0 obj <>stream Advise pregnant women of the potential risk to a fetus. In cases of suspected immune-mediated adverse reactions, initiate appropriate workup to exclude alternative etiologies, including infection. %%EOF 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. Connect with mesothelioma patients around the country who are battling the disease. Initiate treatment with insulin as clinically indicated. Immune-Mediated Nephritis with Renal Dysfunction: Tremelimumab-actl in combination with durvalumab can cause immune-mediated nephritis. There are no data on the presence of tremelimumab-actl in human milk, its effects on a breastfed child, or on milk production. 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 product information is intended for US Healthcare Professionals only. This study used the drug alone rather than in combination with other drugs. Study participants with malignant pleural mesothelioma either received MEDI4736, known as durvalumab, or durvalumab and tremelimumab in this phase 2 trial. Receptors interpret and respond to signals from multiple factors, such as cancerous cells. These more serious side effects include holes in the intestines, obstruction of the small intestine, inflammation of the colon and skin ulcers. 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. 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 Serious adverse reactions occurred in 29% of patients receiving IMFINZI. Immune-mediated Thyroiditis: Immune-mediated thyroiditis occurred in 1.5% (6/388) of patients receiving tremelimumab-actl in combination with durvalumab. We will help you find the best mesothelioma doctor in your area. Events resolved in 5 of the 42 patients. Current clinical trials are testing the drug on multiple types of cancer. The study concluded is estimated to be completed in late 2019. Immune-mediated adverse reactions, which may be severe or fatal, can occur in any organ system or tissue. Institute medical management promptly, including specialty consultation as appropriate. 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). Of the patients who received IMFINZI (475), 1.1% were fatal and 2.7% were Grade 3 adverse reactions. Retrieved from, Guazzelli, A. Immune-mediated adrenal insufficiency occurred in 0.5% (9/1889) of patients receiving IMFINZI, including Grade 3 (<0.1%) adverse reactions. Advise females of reproductive potential to use effective contraception during treatment with tremelimumab-actl and for 3 months after the last dose of the drug. WebTremelimumab is an investigational, fully human IgG monoclonal antibody directed against CTLA-4, a coinhibitory receptor that represses effector T-cell activity in cancer. Two patients (0.5%, 2/388) had events of hyperglycemia requiring insulin therapy that had not resolved at last follow-up. Webc. Massard C, Gordon MS, Sharma S, et al. Tremelimumab is a cancer treatment drug manufactured by AstraZeneca. IMFINZI and IMJUDO can cause immune-mediated colitis that is frequently associated with diarrhea. 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. Serious adverse reactions occurred in 31% of patients receiving IMFINZI plus chemotherapy. Mesothelioma Hub is dedicated to helping you find information, support, and advice. Retrieved on November 14, 2019, from https://clinicaltrials.gov/ct2/show/record/NCT02592551?view=record. CAS number: 745013-59-6. Our pipeline. WebUse in Cancer. Consider administration of other systemic immunosuppressants in patients whose immune-mediated adverse reactions are not controlled with corticosteroid therapy. The following clinically significant, immune-mediated adverse reactions occurred at an incidence of less than 1% each in patients who received IMFINZI and IMJUDO or were reported with the use of other immune-checkpoint inhibitors. Intestinal perforation has been observed in other studies of tremelimumab-actl in combination with durvalumab. Would you like to speak with a Patient Advocate? doi: 10.1080/14737140.2016.1191951, AstraZeneca. Tremelimumab as second- or third-line treatment of unresectable malignant mesothelioma (MM): Results from the global, double-blind, placebo-controlled DETERMINE study. Tremelimumab blocks the activity of CTLA-4, contributing to T-cell activation, priming the immune response to cancer and fostering cancer cell death. Evaluate clinical chemistries including liver enzymes, creatinine, adrenocorticotropic hormone (ACTH) level, and thyroid function at baseline and before each dose. Early results in the Phase 2b study have suggested that the drug fails to improve lifespan. Upon improvement to Grade 1 or less, initiate corticosteroid taper and continue to taper over at least 1 month. Orphan designation does not mean the drug is safe or effective. Thyroiditis can present with or without endocrinopathy. 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. 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). Expert Review of Anticancer Therapy, 16(7), 673675. Early identification and management of immune-mediated adverse reactions are essential to ensure safe use of tremelimumab-actl in combination with durvalumab. Initiate symptomatic treatment including hormone replacement as clinically indicated. Severe and Fatal Immune-Mediated Adverse Reactions 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. Mesothelioma Center - Vital Services for Cancer Patients & Families doesnt believe in selling customer information. Tremelimumab has been tested on a variety of cancers including mesothelioma, lung cancer, melanoma, liver cancer, bladder cancer and head and neck cancer. Immune-mediated colitis or diarrhea occurred in 6% (23/388) of patients receiving IMFINZI and IMJUDO, including Grade 3 (3.6%) adverse reactions. The .gov means its official.Federal government websites often end in .gov or .mil. 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. Advise pregnant women and females of reproductive potential of the potential risk to a fetus. Other (hematologic/immune): Hemolytic anemia, aplastic anemia, hemophagocytic lymphohistiocytosis, systemic inflammatory response syndrome, histiocytic necrotizing lymphadenitis (Kikuchi lymphadenitis), sarcoidosis, and immune thrombocytopenia. Immune-mediated hypothyroidism occurred in 11% (42/388) of patients receiving IMFINZI and IMJUDO. 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 Immune-mediated adrenal insufficiency occurred in 1.5% (6/388) of patients receiving IMFINZI and IMJUDO, including Grade 3 (0.3%) adverse reactions. Verify pregnancy status of females of reproductive potential prior to initiating treatment with tremelimumab-actl. Based on findings from animal studies and its mechanism of action, tremelimumab-actl can cause fetal harm when administered to a pregnant woman. Advise female patients not to breastfeed while taking tremelimumab-actl and for at least 3 months after the last dose. Nearly 37 percent of participants survived at least two years in one of the studies. Information and assistance were provided by The Mesothelioma Center at no cost to our family.". (n.d.). All rights reserved. Immune-mediated adverse reactions can occur at any time after starting treatment or after discontinuation. We comply with the HONcode standard for trustworthy health information. Two patients (2/18) required high-dose corticosteroid treatment (at least 40 mg prednisone or equivalent per day). 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. The effects of local gastrointestinal exposure and limited systemic exposure in the breastfed child to tremelimumab-actl are unknown. After several months, the drug seems to stop working altogether, which is why the FDA hasnt improved it. For Grade 2 or higher adrenal insufficiency, initiate symptomatic treatment, including hormone replacement as clinically indicated. See full Prescribing Information for preparation and administration instructions and dosage modifications for adverse reactions. Around half of the patients lived at least a year in both studies. Immune-mediated rash or dermatitis occurred in 1.8% (34/1889) of patients receiving IMFINZI, including Grade 3 (0.4%) adverse reactions. Lancet Respir Med, 3(4), 301-309. doi: 10.1016/S2213-2600(15)00092-2, Ceresoli, G.L., Bonomi, M., & Sauta, M.G. For those weighing less than 30 kg, the recommended tremelimumab dose is 4 mg/kg IV as a single dose in combination with durvalumab 20 mg/kg IV, followed by durvalumab 20 mg/kg IV every 4 weeks. IMFINZI is indicated for the treatment of adult patients with unresectable Stage III non-small cell lung cancer (NSCLC) whose disease has not. Tremelimumab is considered an immune checkpoint blocker because it blocks a protein called CTLA-4, which deactivates killer T cells. This material is provided for educational purposes only and is not intended for medical advice, diagnosis or treatment. He initially responded quite well. 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 is a human monoclonal antibody and potential new medicine that targets the activity of cytotoxic T-lymphocyte-associated protein 4 (CTLA-4). WebCleviprex is supplied in sterile, pre-mixed, ready-to-use 50 mL or 100 mL vials. 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. 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. 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). Fatal adverse reactions occurred in 8% of patients who received IMJUDO in combination with durvalumab, including death (1%), hemorrhage intracranial (0.5%), cardiac arrest (0.5%), pneumonitis (0.5%), hepatic failure (0.5%), and immune-mediated hepatitis (0.5%). Selby, Karen. WebIMFINZI is indicated for the treatment of adult patients with unresectable Stage III non-small cell lung cancer (NSCLC) whose disease has not IMPORTANT SAFETY INFORMATION There are no contraindications for IMFINZI (durvalumab) or IMJUDO (tremelimumab-actl). Musculoskeletal and connective tissue disorders: Myositis/polymyositis, rhabdomyolysis and associated sequelae including renal failure, arthritis, polymyalgia rheumatica. You may report side effects related to AstraZeneca products by clicking here. %PDF-1.7 % (2006). Retrieved from, National Cancer Institute. 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. That research is underway at several U.S. mesothelioma specialty centers and internationally. 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). A Phase 2 Study of Durvalumab in Combination With Tremelimumab in Malignant Pleural Mesothelioma. Events resolved in 2 of the 6 patients. Selby, Karen. Tremelimumab is a human antibody that helps the immune system fight cancer.