Imfinzi is administered as an intravenous infusion over 60 minutes. Interrupt, slow the rate of, or permanently discontinue Imfinzi based on the severity [see Dosage and Administration (2.2)]. Data sources include IBM Watson Micromedex (updated 3 Mar 2021), Cerner Multum™ (updated 1 Mar 2021), ASHP (updated 3 Mar 2021) and others. PD-L1 and PD-1 knockout mice have also shown decreased survival following infection with lymphocytic choriomeningitis virus. Withhold or permanently discontinue Imfinzi depending on severity [see Dosage and Administration (2.2)]. Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. In animal reproduction studies, administration of durvalumab to cynomolgus monkeys from the onset of organogenesis through delivery resulted in increased premature delivery, fetal loss and premature neonatal death. In animal reproduction studies, administration of … 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%). Toxicity management guidelines for adverse reactions that do not necessarily require systemic steroids (e.g., endocrinopathies and dermatologic reactions) are discussed below. Ask your healthcare provider or pharmacist for more information. Kaplan-Meier Curves of Overall Survival in the PACIFIC Study. Each mL contains durvalumab, 50 mg, L-histidine (2 mg), L-histidine hydrochloride monohydrate (2.7 mg), α,α-trehalose dihydrate (104 mg), Polysorbate 80 (0.2 mg), and Water for Injection, USP. 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). In Patients Who Received Recent Prior Radiation. Systemic corticosteroids were required in all patients with immune-mediated colitis, while 2 patients (2/31) required other immunosuppressants (e.g., infliximab, mycophenolate). Based on its mechanism of action and data from animal studies, IMFINZI can cause fetal harm when administered to a pregnant woman. The evaluation of efficacy for ES-SCLC relied on comparison between: Administration of Imfinzi as a single agent was permitted beyond disease progression if the patient was clinically stable and deriving clinical benefit as determined by the investigator. There are no data on the use of IMFINZI in pregnant … The pharmacokinetics of durvalumab as a single agent was studied in patients with doses ranging from 0.1 mg/kg (0.01 times the approved recommended dosage) to 20 mg/kg (2 times the approved recommended dosage) administered once every two, three, or four weeks. A total of 713 patients were randomized: 476 patients to the Imfinzi arm and 237 to the placebo arm. Discard unused portion. No overall differences in safety or effectiveness were observed between patients 65 years or older and younger patients. The study population characteristics were: median age of 63 years (range: 28 to 82); 40% age 65 or older; 70% male; 84% White, 15% Asian, and 0.9% Black; 65% WHO/ECOG PS of 1; and 93% were former/current smokers. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials. Thyroiditis can present with or without endocrinopathy. Withhold or permanently discontinue Imfinzi based on the severity [see Dosage and Administration (2.2)]. PD-L1 blocks T-cell function and activation through interaction with PD-1 and CD80. The geometric mean (% coefficient of variation [CV%]) steady state volume of distribution (Vss) was 5.6 (18%) L. Durvalumab clearance decreases over time, with a mean maximal reduction (CV%) from baseline values of approximately 23% (57%) resulting in a geometric mean (CV%) steady state clearance (CLss) of 8.2 mL/h (39%) at day 365; the decrease in CLss is not considered clinically relevant. General information about the safe and effective use of Imfinzi. Events resolved in 18 of the 30 patients and resulted in permanent discontinuation in 2 patients. The recommended dose is 10 mg/kg administered as an intravenous infusion over 60 minutes every 2 weeks until disease progression or unacceptable toxicity. There are no data on the use of IMFINZI in pregnant women. Action View Imfinzi mechanism of action for pharmacodynamics and pharmacokinetics details. Some cases can be associated with retinal detachment. Select one or more newsletters to continue. Fatal adverse reactions occurred in 4.9% of patients receiving Imfinzi plus chemotherapy. Immune-Mediated Nephritis with Renal Dysfunction. Do not use if vial seal is broken or missing. Imfinzi can cause immune-mediated pneumonitis. Consider the benefit versus risks of treatment with a PD-1/L-1 blocking antibody prior to or after an allogeneic HSCT. Advise females of reproductive potential to use effective contraception during treatment with Imfinzi and for at least 3 months after the last dose of Imfinzi [see Use in Specific Populations (8.1, 8.3)]. Imfinzi (durvalumab) is a programmed death-ligand 1 (PD-L1) blocking antibody. Based on its mechanism of action and data from animal studies, Imfinzi can cause fetal harm when administered to a pregnant woman. Imfinzi is a medicine that may treat certain cancers by working with your immune system. Durvalumab is a human immunoglobulin G1 kappa (IgG1κ) monoclonal antibody that is produced by recombinant DNA technology in Chinese Hamster Ovary (CHO) cell suspension culture. Transplant-related complications include hyperacute graft-versus-host-disease (GVHD), acute GVHD, chronic GVHD, hepatic veno-occlusive disease (VOD) after reduced intensity conditioning, and steroid-requiring febrile syndrome (without an identified infectious cause). Withhold or permanently discontinue Imfinzi depending on severity [see Dosage and Administration (2.2)]. Durvalumab was administered from the confirmation of pregnancy through delivery at exposure levels approximately 6 to 20 times higher than those observed at the recommended clinical dose of 10 mg/kg (based on AUC). Figure 1. Imfinzi is specifically indicated for the treatment of patients with locally advanced or metastatic urothelial carcinoma who: 1) have disease progression during or following platinum-containing chemotherapy 2) have disease progression within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy Imfinzi is specifically approved for patients with Stage III non-small cell lung cancer who… The most common side effects of Imfinzi in people with NSCLC include: The most common side effects of Imfinzi when used with other anticancer medicines in people with ES-SCLC include: Tell your doctor if you have any side effect that bothers you or that does not go away. The major efficacy outcome measures were progression-free survival (PFS) as assessed by a BICR RECIST v1.1, and overall survival (OS). Cardiac/vascular: Myocarditis, pericarditis, vasculitis. Among 265 patients receiving Imfinzi, 49% were exposed for 6 months or longer and 19% were exposed for 12 months or longer. Imfinzi can cause immune-mediated hepatitis. In general, withhold Imfinzi for severe (Grade 3) immune-mediated adverse reactions. Resume in patients with complete or partial resolution (Grade 0 to 1) after corticosteroid taper. 1 Francis Crick Ave. Given the mechanism of action of IMFINZI, other potential immune-mediated adverse reactions may occur. Systemic corticosteroids were required in all patients with immune-mediated hepatitis, while 1 patient (1/19) required use of mycophenolate with high-dose steroids. Of 2280 patients who received Imfinzi 10 mg/kg every 2 weeks or 20 mg/kg every 4 weeks as a single-agent, 69 patients (3%) tested positive for treatment-emergent anti-drug antibodies (ADA) and 12 (0.5%) tested positive for neutralizing antibodies. Mechanism of action. For Grade 2 or higher adrenal insufficiency, initiate symptomatic treatment, including hormone replacement as clinically indicated. Systemic corticosteroids were required in 3 patients (3/7) with immune-mediated thyroiditis, while 5 patients (5/7) required endocrine therapy. A total of 475 patients received Imfinzi 10 mg/kg intravenously every 2 weeks. Withhold or permanently discontinue Imfinzi based on the severity [see Dosage and Administration (2.2)]. Advise pregnant women of the potential risk to a fetus. The efficacy of Imfinzi was evaluated in the PACIFIC study (NCT02125461), a multicenter, randomized, double-blind, placebo-controlled study in patients with unresectable Stage III NSCLC who completed at least 2 cycles of concurrent platinum-based chemotherapy and definitive radiation within 42 days prior to initiation of the study drug and had a WHO performance status of 0 or 1. Assessment of tumor status was performed every 8 weeks. Administration of durvalumab resulted in premature neonatal death. Keep vial in original carton to protect from light. Blockade of PD-L1/PD-1 and PD-L1/CD80 interactions releases the inhibition of immune responses, without inducing antibody dependent cell mediated cytotoxicity. You can ask your healthcare provider for information about Imfinzi that is written for health professionals. (durvalumab) Table 3 summarizes the adverse reactions that occurred in at least 10% of patients treated with Imfinzi. Urothelial Carcinoma The recommended dose of IMFINZI … The efficacy of Imfinzi in combination with etoposide and either carboplatin or cisplatin in previously untreated ES-SCLC was investigated in CASPIAN, a randomized, multicenter, active-controlled, open-label trial (NCT03043872). In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively. During or following platinum-containing chemotherapy 2. In animal reproduction studies, administration of … The major efficacy outcome measure was overall survival (OS) of Imfinzi plus chemotherapy vs. chemotherapy alone. The data described in this section reflect exposure to Imfinzi in patients with Stage III NSCLC enrolled in the PACIFIC study and in patients with ES-SCLC enrolled in the CASPIAN study. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials [see Clinical Studies (14.1)]. Advise the patient to read the FDA-approved patient labeling (Medication Guide). Topical emollients and/or topical corticosteroids may be adequate to treat mild to moderate non-exfoliative rashes. In these trials, Imfinzi was administered at a dose of 10 mg/kg every 2 weeks. IMFINZI is a medicine that may treat certain cancers by working with your immune system. Imfinzi can cause serious side effects, including: See "What is the most important information I should know about Imfinzi? The endpoints were progression free survival and overall survival. If you would like more information about Imfinzi, talk with your healthcare provider. ... Immune-Mediated Pneumonitis 12.1 Mechanism of Action … The following clinically significant, immune-mediated adverse reactions occurred at an incidence of less than 1% each in patients who received Imfinzi or were reported with the use of other PD-1/PD-L1 blocking antibodies. Injection: 120 mg/2.4 mL (50 mg/mL) and 500 mg/10 mL (50 mg/mL) clear to opalescent, colorless to slightly yellow solution in a single-dose vial. Cambridge, England CB2 0AA Randomization was stratified by the planned platinum-based therapy in cycle 1 (carboplatin or cisplatin). The data described in the Warnings and Precautions section reflect exposure to Imfinzi in 1889 patients from the PACIFIC study (a randomized, placebo-controlled study that enrolled 475 patients with Stage III NSCLC), Study 1108 (an open-label, single-arm, multicohort study that enrolled 970 patients with advanced solid tumors), and an additional open-label, single arm trial that enrolled 444 patients with metastatic lung cancer, an indication for which durvalumab is not approved. The trial excluded patients with active or prior autoimmune disease or with medical conditions that required systemic corticosteroids or immunosuppressants [see Clinical Studies (14.3)]. The most common adverse reactions (occurring in ≥ 20% of patients) were cough, fatigue, pneumonitis or radiation pneumonitis, upper respiratory tract infections, dyspnea, and rash. Imfinzi’s mechanism of action. Tell your healthcare provider about all the medicines you take, We comply with the HONcode standard for trustworthy health information -, Drug class: anti-PD-1 monoclonal antibodies, Voluntary Withdrawal of Imfinzi Indication in Advanced Bladder Cancer in the US. Early identification and management of immune-mediated adverse reactions are essential to ensure safe use of PD-1/PD-L1 blocking antibodies. In animal reproduction studies, administration of durvalumab to pregnant cynomolgus monkeys from the confirmation of pregnancy through delivery resulted in an increase in premature delivery, fetal loss, and premature neonatal death (see Data). These include pancytopenia, sepsis, septic shock, pulmonary artery thrombosis, pulmonary embolism, and hepatitis (1 patient each) and sudden death (2 patients). The major efficacy outcome measures were confirmed Objective Response Rate (ORR) according to RECIST v1.1 as assessed by Blinded Independent Central Review (BICR), and duration of response (DoR). Infusion-related reactions occurred in 2.2% (42/1889) of patients receiving Imfinzi, including Grade 3 (0.3%) adverse reactions. Hypophysitis can present with acute symptoms associated with mass effect such as headache, photophobia, or visual field cuts. Hypothyroidism: Immune-mediated hypothyroidism occurred in 7.3% (137/1889) of patients receiving Imfinzi, including Grade 3 (<0.1%) adverse reactions. 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. ALT or AST increases to more than 3 and up to 8 times the ULN, total bilirubin increases to more than 1.5 and up to 3 times ULN, ALT or AST increases to more than 8 times ULN, total bilirubin increases to more than 3 times the ULN, AST or ALT is more than 1 and up to 3 times ULN at baseline and increases to more than 5 and up to 10 times ULN, AST or ALT is more than 3 and up to 5 times ULN at baseline and increases to more than 8 and up to 10 times ULN, AST or ALT increases to more than 10 times ULN, Total bilirubin increases to more than 3 times ULN, Withhold until clinically stable or permanently discontinue depending on severity, ALT = alanine aminotransferase, AST = aspartate aminotransferase, DRESS = Drug Rash with Eosinophilia and Systemic Symptoms, SJS = Stevens Johnson Syndrome, TEN = toxic epidermal necrolysis, ULN = upper limit normal. The most frequent serious adverse reactions reported in at least 2% of patients were pneumonitis or radiation pneumonitis (7%) and pneumonia (6%). When Imfinzi is administered in combination with chemotherapy, refer to the Prescribing Information for etoposide and carboplatin or cisplatin for dosing information. In mouse allogeneic pregnancy models, disruption of PD-L1 signaling was shown to result in an increase in fetal loss. Figure 2. Systemic corticosteroids were required in all patients with adrenal insufficiency; of these, the majority remained on systemic corticosteroids. Immune-mediated rash or dermatitis occurred in 1.6% (30/1889) of patients receiving Imfinzi, including Grade 3 (0.4%) adverse reactions. In animal models, inhibition of PD-L1/PD-1 signaling increased the severity of some infections and enhanced inflammatory responses. Systemic corticosteroids were required in 9 patients (9/27) with immune-mediated hyperthyroidism, while 21 patients (21/27) required endocrine therapy. View Imfinzi mechanism of action for pharmacodynamics and pharmacokinetics details. Call your doctor for medical advice about side effects. Of the 476 patients treated with Imfinzi in the PACIFIC study, 45% were 65 years or older, while 7.6% were 75 years or older. Systemic corticosteroids were required in all patients with immune-mediated rash or dermatitis. Must dilute before use. Serious adverse reactions occurred in 29% of patients receiving Imfinzi. … Based on its mechanism of action and data from animal studies, IMFINZI can cause fetal harm when administered to a pregnant woman. Detailed clinical and laboratory monitoring guidelines for early detection of adverse reactions of IMFINZI and recommended management are described in the full prescribing information (link below). Hyperthyroidism: Immune-mediated hyperthyroidism occurred in 1.4% (27/1889) of patients receiving Imfinzi. Events resolved in 12 of the 19 patients and resulted in permanent discontinuation of Imfinzi in 4 patients. Manufactured for: AstraZeneca Pharmaceuticals LP, Wilmington, DE 19850, By: AstraZeneca UK Limited, 1 Francis Crick Ave. Cambridge, England CB2 0AA. These complications can be serious and can lead to death. Among 266 patients receiving chemotherapy alone, 57% of the patients received 6 cycles of chemotherapy and 8% of the patients received PCI after chemotherapy. Generic Name: durvalumab Apprise pregnant women of the potential risk to a fetus. Choice of platinum agent was at the investigator’s discretion, taking into consideration the calculated creatinine clearance. However, this approval was withdrawn in February of 2021 following a failure to meet endpoints in the phase 3 post-approval DANUBE clinical study. Exfoliative dermatitis, including Stevens Johnson Syndrome (SJS), drug rash with eosinophilia and systemic symptoms (DRESS), and toxic epidermal necrolysis (TEN), has occurred with PD-1/L-1 blocking antibodies. Imfinzi is a form of immunotherapy containing durvalumab, a monoclonal antibody that blocks programmed cell death ligand-1 (PD-L1). The carcinogenic and genotoxic potential of durvalumab have not been evaluated. Respiratory, thoracic and mediastinal disorders, General disorders and administration site conditions. Durvalumab is a human immunoglobulin G1 kappa (IgG1κ) monoclonal antibody that binds to PD-L1 and blocks the interaction of PD-L1 with PD-1 and CD80 (B7.1). Research by scientists at Götte’s lab found that the use of polymerase enzyme extracted from coronavirus, MERS noting that the enzymes can incorporate … Based on its mechanism of action and data from animal studies, Imfinzi can cause fetal harm when administered to a pregnant woman [see Clinical Pharmacology (12.1)]. IMFINZI is administered as an intravenous infusion over 60 minutes. Durvalumab is a human immunoglobulin G1 kappa (IgG1κ) monoclonal antibody that blocks the interaction of PD-L1 with PD-1 and CD80. The recommended dosages for Imfinzi as a single agent and Imfinzi in combination with chemotherapy are presented in Table 1. Results also showed an increased confirmed objective response rate in the Imfinzi plus SoC arm (68% versus 58% for SoC alone). Hypophysitis can cause hypopituitarism. Mechanism of Action … Dosage modifications for Imfinzi for adverse reactions that require management different from these general guidelines are summarized in Table 2. The pre-specified interim analysis of PFS based on 371 events (81% of total planned events) demonstrated a statistically significant improvement in PFS in patients randomized to Imfinzi compared to placebo. For these reasons, comparison of the incidence of antibodies to durvalumab to the incidence of antibodies to other products may be misleading. Based on National Cancer Institute Common Terminology Criteria for Adverse Events, version 4.03. You can have more than one of these problems at the same time. Based on its mechanism of action and data from animal studies, IMFINZI can cause fetal harm when administered to a pregnant woman. The median time for PFS was 16.8 months for 476 patients receiving Imfinzi compared with 5.6 months for 237 patients receiving placebo. Attention Pharmacist: Dispense the accompanying Medication Guide to each patient. PD-L1 blockade with durvalumab led to increased T-cell activation in vitro and decreased tumor size in co-engrafted human tumor and immune cell xenograft mouse models. Imfinzi (durvalumab) is a human monoclonal antibody that binds to PD-L1 and blocks the interaction of PD-L1 with PD-1 and CD80, countering the tumour's immune-evading tactics … Immune-mediated adrenal insufficiency occurred in 0.4% (7/1889) of patients receiving Imfinzi, including Grade 3 (<0.1%) adverse reactions. PK exposure increased more than dose-proportionally at doses < 3 mg/kg (0.3 times the approved recommended dosage) and dose proportionally at doses ≥ 3 mg/kg every 2 weeks. What is the most important information I should know about Imfinzi? The data also reflect exposure to Imfinzi in combination with chemotherapy in 265 patients from the CASPIAN study (a randomized, open-label study in patients with ES-SCLC). What are the possible side effects of Imfinzi? IMFINZI can cause your immune system to attack normal organs and tissues in any area of your body and can … Other adverse reactions occurring in less than 10% of patients treated with Imfinzi were dysphonia, dysuria, night sweats, peripheral edema, and increased susceptibility to infections. Various grades of visual impairment to include blindness can occur. Initiate treatment with insulin as clinically indicated. Initiate symptomatic treatment including hormone replacement as clinically indicated. Serious adverse reactions occurred in 31% of patients receiving Imfinzi plus chemotherapy. In the chemotherapy alone arm, 57% of the patients received 6 cycles of chemotherapy, and 8% of the patients received PCI. This patient-friendly article is about chemotherapy drug, Durvalumab also known by its trade name Imfinzi; it is used in treating urothelial carcinoma (bladder cancer) and stage III non-small … No dose reduction for Imfinzi is recommended. The OS results are summarized in Table 8 and Figure 2. This FDA approved IMFINZI under accelerated approval for urothelial cancer based on tumor response rate and duration of response. Withhold or permanently discontinue Imfinzi depending on severity, Imfinzi can cause primary or secondary adrenal insufficiency. Last updated on Feb 1, 2021. Your healthcare provider may treat you with corticosteroid or hormone replacement medicines. Imfinzi. These problems can sometimes become severe or life-threatening and can lead to death. Available for Android and iOS devices. The FDA approval of Imfinzi for non-small cell lung cancer was based on the PACIFIC study in 713 patients with unresectable Stage 3 NSCLC who completed at least 2 cycles of concurrent platinum-based chemotherapy and radiation before starting study drug. For Grade 1 or 2 infusion-related reactions, consider using pre-medications with subsequent doses. The event did not lead to permanent discontinuation of Imfinzi. In patients who received Imfinzi on clinical trials in which radiation therapy was generally not administered immediately prior to initiation of Imfinzi, the incidence of immune-mediated pneumonitis was 2% (28/1414), including fatal (<0.1%), and Grade 3-4 (0.4%) adverse reactions. Gastrointestinal: Pancreatitis including increases in serum amylase and lipase levels, gastritis, duodenitis. Events resolved in 3 of the 5 patients and resulted in permanent discontinuation in 4 patients. Signs and symptoms of infusion reactions may include: Complications, including graft-versus-host disease (GVHD), in people who have received a bone marrow (stem cell) transplant that uses donor stem cells (allogeneic). The study excluded patients who had progressed following concurrent chemoradiation, patients with active or prior documented autoimmune disease within 2 years of initiation of the study or patients with medical conditions that required systemic immunosuppression. The most common adverse reactions (occurring in ≥ 20% of patients) were nausea, fatigue/asthenia and alopecia. Age (19–96 years), body weight (31-149 kg), sex, albumin levels, lactate dehydrogenase (LDH) levels, creatinine levels, soluble PD-L1, tumor type, race, mild renal impairment (creatinine clearance (CLcr) 60 to 89 mL/min), moderate renal impairment (CLcr 30 to 59 mL/min), mild hepatic impairment (bilirubin ≤ ULN and AST > ULN or bilirubin > 1 to 1.5x ULN and any AST), or ECOG/WHO performance status had no clinically significant effect on the pharmacokinetics of durvalumab. These are not all of the signs and symptoms of immune system problems that can happen with Imfinzi. ATC Classification . The trial used a fixed dose of Imfinzi(1500 mg) administered every three weeks for four cycles while in combination with chemotherapy and then every four weeks until disease progression as a single medicine. Events resolved in 3 of the 7 patients and none resulted in permanent discontinuation. Important immune-mediated adverse reactions listed under Warnings and Precautions may not include all possible severe and fatal immune-mediated reactions. Due to the potential for serious … Design, CMS, Hosting & Web Development :: ePublishing, Data Integrity for GCP Professionals: Core Requirements, Expectations and Challenges, MAGI's Clinical Research vConference — Spring 2021, Regenerative Medicine: Steps to Accelerate Development, Clinical Trial Agreements: A Guide to Key Words and Phrases, Mid-Study Updates Delay Trials At Least a Month, CSDD Report Finds, Real-Time Data Helped Sponsors Respond to Sites’ Needs During the Pandemic, Increasing Protocol Complexity Requires Adapting Quality Metrics Tools, Ask the Experts: Participant Reimbursement, Compensation and Incentives. Adrenal insufficiency did not lead to permanent discontinuation of Imfinzi in any patients.
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