Merck and Pfizer Inc. (NYSE: PFE) today announced that the European Medicines Agency (EMA) has validated for review the Type II variation application for BAVENCIO^??(avelumab) for first-line maintenance treatment of patients with locally advanced or metastatic urothelial carcinoma (UC). With this validation, the application is complete, and the EMA will now begin the review procedure. The application is based on results from the Phase III JAVELIN Bladder 100 study, which showed a statistically significant improvement in overall survival (OS) for BAVENCIO plus best supportive care (BSC) as first-line maintenance treatment following induction chemotherapy versus BSC alone in patients with locally advanced or metastatic UC. The data were presented at the ASCO 2020 Virtual Scientific Meeting. In the European Union alone, nearly 200,000 people are diagnosed each year with bladder cancer.¹?Urothelial carcinoma accounts for approximately 90 percent of bladder cancers.²?Urothelial carcinoma becomes harder to treat as it advances, spreading through the layers of the bladder wall.³?Despite available therapies, more than 60,000 Europeans die from bladder cancer each year.¹ Earlier this year, the US Food and Drug Administration (FDA) accepted a supplemental Biologics License Application (sBLA) for first-line maintenance treatment of patients with locally advanced or metastatic UC for Priority Review under the agency?s Real-Time Oncology Review (RTOR) pilot program. The FDA also granted Breakthrough Therapy Designation to BAVENCIO for this indication. In addition, a supplemental new drug application has also been accepted by Japan's Ministry of Health, Labour and Welfare for BAVENCIO as a first-line maintenance therapy for locally advanced or metastatic UC. About JAVELIN Bladder 100 JAVELIN Bladder 100 (NCT02603432) is a Phase III, multicenter, multinational, randomized, open-label, parallel-arm study investigating first-line maintenance treatment with BAVENCIO plus BSC versus BSC alone in patients with locally advanced or metastatic UC. A total of 700 patients whose disease had not progressed after platinum-based induction chemotherapy as per RECIST v1.1 were randomly assigned to receive either BAVENCIO plus BSC or BSC alone. The primary endpoint was OS in the two primary populations of all patients and patients with PD-L1+ tumors defined by the Ventana SP263 assay. About BAVENCIO^??(avelumab) BAVENCIO is a human anti-programmed death ligand-1 (PD-L1) antibody. BAVENCIO has been shown in preclinical models to engage both the adaptive and innate immune functions. By blocking the interaction of PD-L1 with PD-1 receptors, BAVENCIO has been shown to release the suppression of the T cell-mediated antitumor immune response in preclinical models.^4-6?In November 2014, Merck and Pfizer announced a strategic alliance to co-develop and co-commercialize BAVENCIO. BAVENCIO Approved Indications The European Commission has authorized the use of BAVENCIO in combination with axitinib for the first-line treatment of adult patients with advanced renal cell carcinoma (RCC). In September 2017, the European Commission granted conditional marketing authorization for BAVENCIO as a monotherapy for the treatment of adult patients with metastatic Merkel cell carcinoma (MCC). In the US, BAVENCIO in combination with axitinib is indicated for the first-line treatment of patients with advanced renal cell carcinoma (RCC). Additionally, the US Food and Drug Administration (FDA) granted accelerated approval for avelumab (BAVENCIO^?) for the treatment of (i) adults and pediatric patients 12 years and older with metastatic Merkel cell carcinoma (mMCC) and (ii) patients with locally advanced or metastatic urothelial carcinoma (mUC) who have disease progression during or following platinum-containing chemotherapy, or have disease progression within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy. These indications are approved under accelerated approval based on tumor response rate and duration of response. Continued approval for these indications may be contingent upon verification and description of clinical benefit in confirmatory trials. BAVENCIO is currently approved for patients with MCC in 50 countries globally, with the majority of these approvals in a broad indication that is not limited to a specific line of treatment. BAVENCIO Safety Profile from the EU Summary of Product Characteristics (SmPC) The special warnings and precautions for use for BAVENCIO monotherapy include infusion-related reactions, as well as immune-related adverse reactions that include pneumonitis and hepatitis (including fatal cases), colitis, pancreatitis (including fatal cases), myocarditis (including fatal cases), endocrinopathies, nephritis and renal dysfunction, and other immune-related adverse reactions. The special warnings and precautions for use for BAVENCIO in combination with axitinib include hepatotoxicity. The SmPC list of the most common adverse reactions with BAVENCIO monotherapy in patients with solid tumors includes fatigue, nausea, diarrhea, decreased appetite, constipation, infusion-related reactions, weight decreased and vomiting. The list of most common adverse reactions with BAVENCIO in combination with axitinib includes diarrhea, hypertension, fatigue, nausea, dysphonia, decreased appetite, hypothyroidism, cough, headache, dyspnea, and arthralgia. References 1.??????? Cancer Today. Estimated number of new cases in 2018, Europe, both sexes, all ages.?https://gco.iarc.fr/today/online-analysis-tables. Accessed June 2020. 2.??? Cancer.net. Bladder cancer: introduction.?https://www.cancer.net/cancer-types/bladder-cancer/introduction. Accessed June 2020. 3.??? American Cancer Society. What is bladder cancer??https://www.cancer.org/cancer/bladder-cancer/about/what-is-bladder-cancer.html. Accessed June 2020. 4.??? Dolan DE, Gupta S. PD-1 pathway inhibitors: changing the landscape of cancer immunotherapy.?Cancer Control. 2014;21(3):231-237. 5.??? Dahan R, Sega E, Engelhardt J, et al. Fc?Rs modulate the anti-tumor activity of antibodies targeting the PD-1/PD-L1 axis.?Cancer Cell. 2015;28(3):285-295. 6.??? Boyerinas B, Jochems C, Fantini M, et al. Antibody-dependent cellular cytotoxicity activity of a novel anti-PD-L1 antibody avelumab (MSB0010718C) on human tumor cells.?Cancer Immunol Res.?2015;3(10):1148-1157.