A Phase 2 Study of Durvalumab in Combination With Tremelimumab in Malignant Pleural Mesothelioma. IMFINZI and IMJUDO can cause immune-mediated nephritis. Asbestos.com. IMFINZI and IMJUDO are registered trademarks and AstraZeneca Access 360 is a trademark of the AstraZeneca group of companies. Consider the benefit versus risks of treatment with a PD-1/L-1 blocking antibody prior to or after an allogeneic HSCT. Efficacy and safety of an intensified schedule of tremelimumab for chemotherapy-resistant malignant mesothelioma: an open-label, single-arm, phase 2 study. IMFINZI and IMJUDO can cause immune-mediated pneumonitis, which may be fatal. 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. 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. You may report side effects related to AstraZeneca products by clicking here. 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. Refer to the prescribing information for agents administered in combination with tremelimumab-actl for breastfeeding recommendations, as appropriate. Definition of tremelimumab. 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. This review used the Assessment Aid, a voluntary submission from the applicant to facilitate the FDAs assessment. There is no information regarding the presence of IMFINZI and IMJUDO in human milk; however, because of the potential for serious adverse reactions in breastfed infants from IMFINZI and IMJUDO, advise women not to breastfeed during treatment and for 3 months after the last dose. Any unauthorized or illegal use, copying or dissemination will be prosecuted. Medications like tremelimumab are designed to fight cancer cells by increasing the amount of activated killer T cells. (2015). A Study of Tremelimumab Combined With the Anti-PD-L1 MEDI4736 Antibody in Malignant Mesothelioma (NIBIT-MESO-1). Immune-mediated adverse reactions can occur at any time after starting tremelimumab-actl in combination with durvalumab. Interrupt, slow the rate of, or permanently discontinue tremelimumab-actl and durvalumab based on the severity. Withhold or discontinue tremelimumab-actl in combination with durvalumab based on the severity. The most common (20%) adverse reactions occurring in patients were rash, diarrhea, fatigue, pruritis, musculoskeletal pain and abdominal pain. Seventeen patients required other therapy (thiamazole, carbimazole, propylthiouracil, perchlorate, calcium channel blocker, or beta-blocker). Intestinal perforation and large intestine perforation were reported in 0.1% of patients. Immune-Mediated Hepatitis: Tremelimumab-actl in combination with durvalumab can cause immune-mediated hepatitis, which may be fatal. IMFINZI and IMJUDO can cause immune-mediated rash or dermatitis. 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. Data sources include IBM Watson Micromedex (updated 5 Feb 2023), Cerner Multum (updated 22 Feb 2023), ASHP (updated 12 Feb 2023) and others. 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. Massard C, Gordon MS, Sharma S, et al. 8 It binds to its target, human CTLA-4, with high selectivity 2 and subnanomolar affinity. However, combining tremelimumab and durvalumab has proven more effective against lung cancer than tremelimumab alone. IMFINZI in combination with IMJUDO can cause immune-mediated pancreatitis. Webc. Request free informational, treatment, financial or support resources to help you and your loved one after a mesothelioma diagnosis. Clinical trials on tremelimumab have been conducted on cancer patients in an attempt to study the prevention, detection, or treatment of multiple diseases. Retrieved from, National Cancer Institute. Last Modified: September 22, 2022, Created: July 6, 2022. Nervous system: Meningitis, encephalitis, myelitis and demyelination, myasthenic syndrome/myasthenia gravis (including exacerbation), Guillain-Barr syndrome, nerve paresis, autoimmune neuropathy. Tremelimumab may help people live longer with mesothelioma, but the drug may also cause side effects. IMFINZI is indicated for the treatment of adult patients with unresectable Stage III non-small cell lung cancer (NSCLC) whose disease has not progressed following concurrent platinum-based chemotherapy and radiation therapy. Initial studies of the drug produced impressive results that havent been replicated in larger clinical trials. WebIMJUDO (tremelimumab-actl) injection, for intravenous use Initial U.S. Approval: 2022----- INDICATIONS AND USAGE -----IMJUDOis a cytotoxic T-lymphocyte-associated See USPI Dosing and Administration for specific details. (2015, October 27). 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. et al. Immune-mediated pneumonitis occurred in 1.3% (5/388) of patients receiving IMFINZI and IMJUDO, including fatal (0.3%) and Grade 3 (0.2%) adverse reactions. IMFINZI, in combination with gemcitabine and cisplatin, is indicated for the treatment of adult patients with locally advanced or metastatic biliary tract cancer (BTC). Immune-mediated hepatitis occurred in 2.8% (52/1889) of patients receiving IMFINZI, including fatal (0.2%), Grade 4 (0.3%) and Grade 3 (1.4%) adverse reactions. Infusion-related reactions occurred in 10 (2.6%) patients receiving IMFINZI and IMJUDO. Our pipeline. Advise pregnant women and females of reproductive potential of the potential risk to a fetus. Drug class: Antineoplastic Agents WebTREMFYA is a clear and colorless to light yellow solution that may contain small translucent particles. endstream endobj startxref In 2017, mesothelioma survivor and Navy veteran Jim McWhorter joined a clinical trial testing tremelimumab and durvalumab, another immunotherapy drug. Pneumonitis: Advise patients to contact their healthcare provider immediately for any new or worsening cough, chest pain, or shortness of breath. The site is secure. 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; The .gov means its official.Federal government websites often end in .gov or .mil. Researchers estimate the study will be completed in late 2019. 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. 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). Retrieved on November 14, 2019, from https://www.cancer.gov/publications/dictionaries/cancer-drug/def/tremelimumab, Ribas, A., et. 5 WARNINGS AND PRECAUTIONS The information on this website is proprietary and protected. Hypophysitis can cause hypopituitarism. Our Patient Advocates have relationships with top doctors and cancer centers and can help you schedule and expedite appointments. Tremelimumab as second- or third-line treatment of unresectable malignant mesothelioma (MM): Results from the global, double-blind, placebo-controlled DETERMINE study. 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). Endocrinopathies: Advise patients to contact their healthcare provider immediately for signs or symptoms of hypothyroidism, hyperthyroidism, adrenal insufficiency, type 1 diabetes mellitus, or hypophysitis. Monitor patients closely for symptoms and signs that may be clinical manifestations of underlying immune-mediated adverse reactions. Most common adverse reactions ( 20%) of patients with uHCC receiving tremelimumab-actl are rash, diarrhea, fatigue, pruritus, musculoskeletal pain, and abdominal pain. Pediatric . After several months, the drug seems to stop working altogether, which is why the FDA hasnt improved it. "My family has only the highest compliment for the assistance and support that we received from The Mesothelioma Center. Both durvalumab and tremelimumab have been tested for mesothelioma alone, but not in combination. Cytomegalovirus (CMV) infection/reactivation has been reported in patients with corticosteroid-refractory immune-mediated colitis. The drugs stopped his tumor growth for months. Topical emollients and/or topical corticosteroids may be adequate to treat mild to moderate non-exfoliative rashes. Monoclonal antibody drugs for cancer: How they work. Imjudo blocks the Additional efficacy outcomes included investigator-assessed progression-free survival (PFS) and overall response rate (ORR) according to RECIST v1.1. The most frequent serious adverse reactions (2%) were pneumonitis or radiation pneumonitis (7%) and pneumonia (6%). Immune-mediated adrenal insufficiency occurred in 1.5% (6/388) of patients receiving IMFINZI and IMJUDO, including Grade 3 (0.3%) adverse reactions. Drugs.com provides accurate and independent information on more than 24,000 prescription drugs, over-the-counter medicines and natural products. In synergistic mouse tumor models, blocking CTLA-4 activity resulted in decreased tumor growth and increased proliferation of T cells in tumors. These complications may occur despite intervening therapy between PD-1/L-1 blockade and allogeneic HSCT. Tremelimumab is an immunotherapy drug that helps the immune system block cancerous cells. Antibodies are proteins produced by plasma cells that the immune system by attaching themselves to molecules on the surface of problematic cells. In a murine model of pregnancy, CTLA-4 blockade resulted in increased resorptions and reduced live fetuses. Each infusion will take approximately 1 hour. Around half of the patients lived at least a year in both studies. Of the patients who received IMFINZI (475), 1.1% were fatal and 2.7% were Grade 3 adverse reactions. All patients required other therapy (thiamazole, carbimazole, propylthiouracil, perchlorate, calcium channel blocker, or beta-blocker). Antibodies are proteins in the immune system that recognize and attack foreign invaders such as bacteria, viruses and cancer cells. The trial was suspended in late 2019 after criteria were not met, but doctors and researchers estimate completion in 2024. Cardiac/vascular: Myocarditis, pericarditis, vasculitis. For additional information until a more detailed monograph is developed and published, the manufacturer's labeling should be consulted. Tremelimumab is considered an immune checkpoint blocker because it blocks a protein called CTLA-4, which deactivates killer T cells. One cycle is defined as every 4 weeks. Available for Android and iOS devices. If receiving both durvalumab and tremelimumab for the first 4 cycles, they will be given on the same day. The safety and effectiveness of IMFINZI and IMJUDO have not been established in pediatric patients. Advise patients to contact their healthcare provider immediately for signs or symptoms of infusion-related reactions. The results led the researchers to conclude that the treatment combination was associated with long-term survival. He initially responded quite well. If youre still feeling overwhelmed, let us help you seek the advice you need. 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. Grade 3 immune-mediated Type 1 diabetes mellitus occurred in <0.1% (1/1889) of patients receiving IMFINZI. WebUse in Cancer. Antibodies are proteins in the immune system that recognize and attack foreign Based on findings from animal studies and its mechanism of action, tremelimumab-actl can cause fetal harm when administered to a pregnant woman. 5-Year Mesothelioma Survivor Motivated by Family, Mesothelioma Survivors Treatment Journey Continues, A Post-Cancer Letter to Pre-Cancer Tamron. Two patients (0.5%, 2/388) had events of hyperglycemia requiring insulin therapy that had not resolved at last follow-up. Tremelimumab is a human monoclonal antibody and potential new medicine that targets the activity of cytotoxic T-lymphocyte-associated protein 4 (CTLA-4). Tremelimumab is a cancer treatment drug manufactured by AstraZeneca. Advise the patient to read the FDA-approved patient labeling (Medication Guide). 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. In cases of corticosteroid-refractory colitis, consider repeating infectious workup to exclude alternative etiologies. In 2021, a clinical research study followed up with mesothelioma patients four years after they received tremelimumab and durvalumab. Serious adverse reactions occurred in 29% of patients receiving IMFINZI. Two patients (2/18) required high-dose corticosteroid treatment (at least 40 mg prednisone or equivalent per day). Immune-mediated adrenal insufficiency occurred in 0.5% (9/1889) of patients receiving IMFINZI, including Grade 3 (<0.1%) adverse reactions. Weve gathered all of our resources into one guide with one purpose: helping you navigate mesothelioma. Tremelimumab has been tested on a variety of cancers including mesothelioma, lung cancer, melanoma, liver cancer, bladder cancer and head and neck cancer. 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. Immune-mediated rash or dermatitis occurred in 7.2% (43/596) of patients receiving IMFINZI in combination with IMJUDO in combination with platinum-based chemotherapy, including Grade 3 (0.3%) adverse reactions. If you are looking for mesothelioma support, please contact our Patient Advocates at (855) 404-4592. View full prescribing information for Imjudo. Infusion-related reactions occurred in 10 (2.6%) patients receiving tremelimumab-actl in combination with durvalumab. 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. Immune-mediated nephritis occurred in 1% (4/388) of patients receiving tremelimumab-actl in combination with durvalumab, including Grade 3 (0.5%) adverse reactions. 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 Mesothelioma Center - Vital Services for Cancer Patients & Families doesnt believe in selling customer information. For example, two small Italian studies reported tremelimumab stopped cancer growth in about half of the mesothelioma participants. Researchers suggested more trials that combine drugs are necessary to see how well tremelimumab may work against mesothelioma. This website and its content may be deemed attorney advertising. Retrieved on November 14, 2019, from https://www.cancer.gov/about-cancer/treatment/clinical-trials/intervention/tremelimumab?redirect=true, National Cancer Institute. Events resolved in 15 of the 18 patients. WebOn October 21, 2022, the Food and Drug Administration approved tremelimumab (Imjudo, AstraZeneca Pharmaceuticals) in combination with durvalumab for adult patients with Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details. An official website of the United States government, : 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. 1 Tremelimumab caused increased IL-2 production in a dose-dependent manner in ex-vivo blood stimulation assays using peripheral blood Advise pregnant women and females of reproductive potential of the potential risk to a fetus. Wilmington, DE; AstraZeneca Pharmaceuticals LP; November 2022. The effects of local gastrointestinal exposure and limited systemic exposure in the breastfed child to tremelimumab-actl are unknown. 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. Asbestos.com is sponsored by law firms. 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%). 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. %%EOF Initiate symptomatic treatment including hormone replacement as clinically indicated. Events resolved in 3 of the 4 patients and resulted in permanent discontinuation in 2 patients. Current clinical trials are testing the drug on multiple types of cancer. 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. 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 Retrieved from. She hopes to create public awareness about cancer through her writing. The problem is tremelimumab seems to work well for only a little while. Hypothyroidism can follow hyperthyroidism. Verify pregnancy status of females of reproductive potential prior to initiating treatment with tremelimumab-actl. Would you like to speak with a Patient Advocate? Several landmark trials have shown tremelimumab can stop mesothelioma tumors from growing for periods of time. In animal studies, CTLA-4 blockade is associated with higher incidence of pregnancy loss. 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). Clinical trials are testing the drug on several different cancers including mesothelioma. Toxicity management guidelines for adverse reactions that do not necessarily require systemic steroids (e.g., endocrinopathies and dermatologic reactions) are discussed below. 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. There are no contraindications for IMFINZI (durvalumab) or IMJUDO (tremelimumab-actl). Tremelimumab, manufactured by AstraZeneca, is an immunotherapy treatment that helps the immune system recognize and attack cancer cells. An orphan drug typically treats uncommon illnesses, and cannot make much of a profit. 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 Retrieved from, ClinicalTrials.gov. Good research has proven it isnt effective enough on its own to use as a single therapy against mesothelioma. Pharmacodynamics. 301 0 obj <> endobj Tremelimumab is a human antibody that helps the immune system fight cancer. Tremelimumab is a monoclonal antibody drug, which is a type of treatment that helps the immune system fight cancer. 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. The tremelimumab antibody activates an immune cell known as cytotoxic T lymphocytes (CTLs), or killer T cells. Immune-Mediated Adrenal Insufficiency: Tremelimumab-actl in combination with durvalumab can cause primary or secondary adrenal insufficiency. Calling this number connects you with a Patient Advocate at The Mesothelioma Center, the nation's most trusted mesothelioma resource. Two patients (0.5%, 2/388) had events of hyperglycemia requiring insulin therapy that had not resolved at last follow-up. More than 30 contributors, including mesothelioma doctors, survivors, health care professionals and other experts, have peer-reviewed our website and written unique research-driven articles to ensure you get the highest-quality medical and health information. Events resolved in 6 of the 9 patients. 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. 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. 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.