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US FDA Accepts Supplemental Biologics License Application for IMFINZI® (durvalumab) in Locally Advanced, Unresectable Non-Small Cell Lung CancerAstraZeneca and MedImmune, its global biologics research and development arm, today announced that the US Food and Drug Administration (FDA) has accepted a supplemental Biologics License Application (sBLA) for IMFINZI® (durvalumab) for the treatment of patients with locally advanced, unresectable non-small cell lung cancer (NSCLC) whose disease has not progressed following platinum-based chemoradiation therapy. The FDA has granted IMFINZI Priority Review status. The US FDA sBLA submission acceptance is an important milestone for IMFINZI in a disease state where patients need better treatment options and outcomes. Currently, the standard of care for these patients with locally advanced (Stage III) lung cancer is active monitoring following definitive chemoradiation. The sBLA submission is based on positive progression-free survival (PFS) data from the Phase III PACIFIC trial. The trial continues to evaluate overall survival (OS), its other primary endpoint. Detailed results of the PACIFIC trial, including additional safety information, were published online in the New England Journal of Medicine. On September 28, 2017, the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) were updated to include durvalumab for the treatment of patients with locally advanced, unresectable NSCLC with no disease progression after two or more cycles of definitive chemoradiation, based on the data from the PACIFIC Phase III trial. This indication is not yet FDA-approved. IMFINZI has already received accelerated approval in the US for the treatment of patients with locally advanced or metastatic urothelial carcinoma, who have disease progression during or following platinum-containing chemotherapy, or whose disease has progressed within 12 months of receiving platinum-containing chemotherapy before (neoadjuvant) or after (adjuvant) surgery. IMPORTANT SAFETY INFORMATION There are no contraindications for IMFINZI® (durvalumab). Monitor patients for clinical signs and symptoms of immune-mediated pneumonitis, hepatitis, colitis or diarrhea, endocrinopathies, nephritis, rash or dermatitis, other immune-mediated adverse reactions, and infection. Please refer to the full Prescribing Information for important dose management information specific to adverse reactions. Immune-Mediated Pneumonitis In the combined safety database (n=1414), immune-mediated pneumonitis occurred in 32 patients (2.3%), including 1 fatal case (0.1%) and 6 Grade 3-4 cases (0.4%). In Study 1 (n=182), 1 patient (0.5%) died from immune-mediated pneumonitis. Monitor patients for signs and symptoms of pneumonitis and evaluate with radiographic imaging when suspected. Administer corticosteroids for =Grade 2 pneumonitis. Withhold IMFINZI for Grade 2 pneumonitis; permanently discontinue for Grade 3-4 pneumonitis. Immune-Mediated Hepatitis In the combined safety database (n=1414), immune-mediated hepatitis occurred in 16 patients (1.1%), including 1 fatal case (<0.1%) and 9 Grade 3 cases (0.6%). Grade 3-4 elevations in ALT occurred in 40/1342 patients (3.0%), AST in 58/1336 patients (4.3%), and total bilirubin in 37/1341 patients (2.8%). In Study 1 (n=182), 1 patient (0.5%) died from immune-mediated hepatitis, and 2 patients (1.1%) experienced immune-mediated hepatitis, including 1 Grade 3 case (0.5%). Monitor patients for abnormal liver tests in each cycle during treatment with IMFINZI. Administer corticosteroids and withhold IMFINZI for Grade 2-3 ALT or AST >3-5X ULN or =8X ULN or total bilirubin >1.5-3X ULN or =5X ULN. Permanently discontinue IMFINZI in patients with Grade 3 ALT or AST >8X ULN or total bilirubin >5X ULN, or in patients with concurrent ALT or AST >3X ULN and total bilirubin >2X (News - Alert) ULN with no other cause. Immune-Mediated Colitis In the combined safety database (n=1414), immune-mediated colitis or diarrhea occurred in 18 patients (1.3%), including 1 Grade 4 case (<0.1%) and 4 Grade 3 cases (0.3%). In Study 1 (n=182), 23 patients (12.6%) experienced colitis or diarrhea, including 2 Grade 3-4 cases (1.1%). Monitor patients for signs and symptoms of colitis or diarrhea. Administer corticosteroids for =Grade 2 colitis or diarrhea. Withhold IMFINZI for Grade 2 colitis or diarrhea; permanently discontinue for Grade 3-4 colitis or diarrhea. Immune-Mediated Endocrinopathies
Infection Severe infections, including sepsis, necrotizing fasciitis, and osteomyelitis, occurred in patients receiving IMFINZI. In the combined safety database (n=1414), infections occurred in 531 patients (37.6%). In Study 1 (n=182), infections occurred in 54 patients (29.7%). 11 patients (6.0%) experienced Grade 3-4 infection and 5 patients (2.7%) were experiencing infection at the time of death. 8 patients (4.4%) experienced urinary tract infection, the most common =Grade 3 infection. Monitor patients for signs and symptoms of infection and treat with anti-infectives for suspected or confirmed infections. Withhold IMFINZI for =Grade 3 infection. Infusion-Related Reactions In the combined safety database (n=1414), severe infusion-related reactions occurred in 26 patients (1.8%). In Study 1 (n=182), infusion-related reactions occurred in 3 patients (1.6%). There were 5 Grade 3 (0.4%) and no Grade 4 or 5 reactions. Patients should be monitored for signs and symptoms of infusion-related reactions. Interrupt or slow the rate of infusion for Grade 1-2 infusion-related reactions and permanently discontinue for Grade 3-4 infusion-related reactions. Embryo-Fetal Toxicity Based on its mechanism of action and data from animal studies, IMFINZI can cause fetal harm when administered to a pregnant woman. There are no data on the use of IMFINZI in pregnant women. Advise pregnant women of the potential risk to a fetus and advise women of reproductive potential to use effective contraception during treatment and for at least 3 months after the last dose of IMFINZI. Nursing Mothers There is no information regarding the presence of IMFINZI in human milk; however, because of the potential for adverse reactions in breastfed infants from IMFINZI, advise a lactating woman not to breastfeed during treatment and for at least 3 months after the last dose. Most Common Adverse Reactions
The safety and effectiveness of IMFINZI have not been established in pediatric patients. Please see complete Prescribing Information including Patient Information. NOTES TO EDITORS About Locally Advanced (Stage III) NSCLC Locally advanced (Stage III) lung cancer is divided into three sub-categories (IIIA, IIIB and IIIC), which are defined by how much the cancer has spread locally and the possibility of surgery. This differentiates it from Stage IV disease, when the cancer has spread (metastasized) to distant organs. Approximately one in four patients with non-small cell lung cancer present with locally advanced (Stage III) disease, which is estimated to affect over 43,000 patients annually in the United States. About half of these patients have tumors that are unresectable. The current standard of care is chemotherapy and radiation followed by active surveillance to monitor for progression. The prognosis remains poor and long-term survival rates are low. About PACIFIC The PACIFIC trial is a randomized, double-blind, placebo-controlled, multi-center trial of durvalumab as sequential treatment in unselected patients with locally advanced, unresectable (Stage III) non-small cell lung cancer who have not progressed following platinum-based chemotherapy concurrent with radiation therapy. The trial involved 235 centers across 26 countries, including approximately 700 patients. The primary endpoints of the trial are progression-free survival (PFS) and overall survival (OS), and secondary endpoints include landmark PFS and OS, objective response rate, duration of response and time to death or distant metastases. About IMFINZI® (durvalumab) IMFINZI® (durvalumab) is a human monoclonal antibody directed against PD-L1, which blocks the interaction of PD-L1 with PD-1 and CD80. IMFINZI has already received accelerated approval in the US for the treatment of patients with locally advanced or metastatic urothelial carcinoma, who have disease progression during or following platinum-containing chemotherapy, or whose disease has progressed within 12 months of receiving platinum-containing chemotherapy before (neoadjuvant) or after (adjuvant) surgery. This indication is approved under accelerated approval based on tumor response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials. As part of a broad development program, durvalumab is also being investigated for the adjuvant treatment of patients with NSCLC in the CCTG (Canadian Cancer Trials Group) trial ADJUVANT (BR31). In the MYSTIC, NEPTUNE, and PEARL Phase III trials, durvalumab is being studied for 1st-line treatment as monotherapy and/or in combination with tremelimumab, an anti-CTLA-4 monoclonal antibody, for the treatment of metastatic NSCLC. The POSEIDON trial is investigating durvalumab with and without tremelimumab in combination with chemotherapy in the same population. About AstraZeneca in Lung Cancer AstraZeneca is committed to developing therapies to help every patient with lung cancer. We have two approved therapies and a growing pipeline that targets genetic changes in tumor cells and boosts the power of the immune response against cancer. Our unrelenting pursuit of science aims to deliver more breakthrough therapies with the goal of extending and improving the lives of patients across all stages of disease and lines of therapy. About AstraZeneca's Approach to Immuno-Oncology Immuno-Oncology (IO) is a therapeutic approach designed to stimulate the body's immune system to attack tumors. At AstraZeneca and MedImmune, our biologics research and development arm, our IO portfolio is anchored by immunotherapies that have been designed to overcome anti-tumor immune suppression. We believe that IO-based therapies will offer the potential for life-changing cancer treatments for the vast majority of patients. We are pursuing a comprehensive clinical trial program that includes durvalumab (anti-PD-L1 antibody) monotherapy and in combination with tremelimumab (anti-CTLA-4 antibody) in multiple tumor types, stages of disease, and lines of therapy, using the PD-L1 biomarker as a decision-making tool to define the best potential treatment path for a patient. In addition, the ability to combine our IO portfolio with small, targeted molecules from across our oncology pipeline, and with those of our research partners, may provide new treatment options across a broad range of tumors. About AstraZeneca in Oncology AstraZeneca has a deep-rooted heritage in Oncology and offers a quickly growing portfolio of new medicines that has the potential to transform patients' lives and the Company's future. With at least six new medicines to be launched between 2014 and 2020, and a broad pipeline of small molecules and biologics in development, we are committed to advance New Oncology as one of AstraZeneca's five Growth Platforms focused on lung, ovarian, breast and blood cancers. In addition to our core capabilities, we actively pursue innovative partnerships and investments that accelerate the delivery of our strategy as illustrated by our investment in Acerta Pharma in hematology. By harnessing the power of four scientific platforms - Immuno-Oncology, Tumor Drivers and Resistance, DNA Damage Response and Antibody Drug Conjugates - and by championing the development of personalized combinations, AstraZeneca has the vision to redefine cancer treatment and one day eliminate cancer as a cause of death. About MedImmune MedImmune is the global biologics research and development arm of AstraZeneca, a global, innovation-driven biopharmaceutical business that focuses on the discovery, development and commercialization of small molecule and biologic prescription medicines. MedImmune is pioneering innovative research and exploring novel pathways across Oncology; Respiratory, Cardiovascular & Metabolic Diseases; and Infection and Vaccines. The MedImmune headquarters is located in Gaithersburg, MD, one of AstraZeneca's three global R&D centers, with additional sites in Cambridge, UK, and Mountain View, CA (News - Alert). For more information, please visit www.medimmune.com. About AstraZeneca AstraZeneca is a global, science-led biopharmaceutical company that focuses on the discovery, development and commercialization of prescription medicines, primarily for the treatment of diseases in three main therapy areas - Oncology, Cardiovascular & Metabolic Diseases and Respiratory. The Company also is selectively active in the areas of autoimmunity, neuroscience and infection. AstraZeneca operates in over 100 countries and its innovative medicines are used by millions of patients worldwide. For more information, please visit www.astrazeneca-us.com and follow us on Twitter (News - Alert) @AstraZenecaUS. US-15091 Last Updated 10/17
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