? Approved as the first cancer immunotherapy-based combination demonstrating efficacy in treating hepatocellular carcinoma (HCC) ? Approval is based on the results from the global phase III IMbrave150 study in patients with unresectable hepatocellular carcinoma without prior systemic therapy TOKYO, September 25, 2020 -- Chugai Pharmaceutical Co., Ltd. (TOKYO: 4519) announced that it obtained approval for an additional indication of Tecentriq? Intravenous Infusion 1200 mg [generic name: atezolizumab (genetical recombination)], an anti-cancer agent/humanized anti-PD-L1 monoclonal antibody, and Avastin? Intravenous Infusion 100 mg/4 mL and 400 mg/16 mL [generic name: bevacizumab (genetical recombination)], an anti-cancer agent/humanized anti-VEGF monoclonal antibody, for the treatment of unresectable hepatocellular carcinoma (HCC) from the Ministry of Health, Labour and Welfare (MHLW). The combination therapy was designated for priority review from the MHLW in April 2020 based on the positive data showing improvement of prognosis, which subsequently led to the approval seven months after the filing of the application. ?I am very pleased that the combination therapy of Tecentriq and Avastin has been approved for the treatment of HCC in patients with poor prognosis and limited treatment options,? said Dr. Osamu Okuda, Chugai?s President & COO. ?I feel both pleasure and responsibility for the delivery of this treatment to patients as the first cancer immunotherapy that demonstrated efficacy in treating HCC. Chugai will continue its efforts to promptly provide information on proper use to contribute to the development of treatment for the disease.? The approval is based on the results from the global phase III IMbrave150 study in patients with unresectable HCC without prior systemic therapy. The combination of Tecentriq and Avastin reduced the risk of death by 42% (OS hazard ratio: 0.58; 95%CI: 0.42-0.79; p = 0.0006 [stratified log-rank test]) and reduced the risk of disease worsening or death by 41% (PFS hazard ratio: 0.59; 95%CI: 0.47-0.76; p< 0.0001 [stratified log-rank test]) compared to sorafenib monotherapy. Adverse reactions were observed in 276 of 329 (83.9%) patients treated with Tecentriq and Avastin. The most frequent (10% or more) adverse reactions included; hypertension, proteinuria, fatigue, increased AST, pruritus, infusion-related reaction, diarrhea, increased ALT, and decreased appetite. The results of the study have been published in the New England Journal of Medicine on May 14, 2020. ?Chugai Files for Additional Indications of Tecentriq and Avastin for the Treatment of Unresectable Hepatocellular Carcinoma (A press release issued by Chugai in February 14, 2020) 2 / 3 https://www.chugai-pharm.co.jp/english/news/detail/20200214150000_700.html ? Roche presents pivotal data demonstrating Tecentriq in combination with Avastin improves overall survival in people with the most common form of liver cancer (A press release issued by Roche in November 22, 2019) https://www.roche.com/media/releases/med-cor-2019-11-22b.htm ?Tecentriq in Combination with Avastin Increases Overall Survival and Progression-free Survival as an Initial Treatment in People with Unresectable Hepatocellular Carcinoma (A press release issued by Chugai in October 21, 2019) https://www.chugai-pharm.co.jp/english/news/detail/20191021171500_657.html As a leading company in the field of oncology, Chugai will continue to promote proper use of Tecentriq so that it can contribute to the treatment of unresectable HCC as one of new therapeutic options. Prescribing Information *Excerpt version Brand name: Tecentriq? Intravenous Infusion 1200 mg Generic name: atezolizumab (genetical recombination) Indications: Unresectable hepatocellular carcinoma Dosage and administration: The usual adult dosage is 1200 mg atezolizumab (genetical recombination) in combination with bevacizumab administered by intravenous infusion over 60 minutes once every 3 weeks. If the initial infusion is well tolerated, subsequent infusions can be delivered over 30 minutes. Brand name: Avastin? Intravenous Infusion 100 mg/4 mL and 400 mg/16 mL Generic name: bevacizumab (genetical recombination) Indications: Unresectable hepatocellular carcinoma Dosage and administration: The usual adult dosage is 15 mg/kg (body weight) of bevacizumab (genetical recombination) in combination with atezolizumab administered by intravenous infusion. The dosing interval should be 3 weeks or longer. About IMbrave150 study IMbrave150 is a global Phase III, multicenter, open-label study of 501 people with unresectable HCC who have not received prior systemic therapy. People were randomized 2:1 to receive the combination of Tecentriq and Avastin or sorafenib. People received the combination or the control arm treatment until unacceptable toxicity or loss of clinical benefit as determined by the investigator. Co-primary endpoints were overall survival (OS) and progression free survival (PFS) by independent-review facility (IRF) per RECIST v1.1. Secondary efficacy endpoints included objective response rate (ORR), time to progression (TTP) and duration of response (DOR) as well as patient-reported outcomes (PROs), safety and pharmacokinetics. About hepatocellular carcinoma (HCC) HCC accounts for over 90% of liver cancer and is an aggressive type of cancer with limited treatment 3 / 3 options hence it is a major cause of cancer deaths worldwide.1, 2) In Japan, about 40,000 people are diagnosed with liver cancer every year and the number of deaths accounts for about 28,000 per year.3) HCC develops predominantly in people with cirrhosis due to chronic hepatitis (B or C) or alcohol consumption, and typically presents at an advanced stage.1) The prognosis for unresectable HCC remains limited, with few systemic therapeutic options and a 1-year survival rate of less than 50%.4) Trademarks used or mentioned in this release are protected by law. [References] 1: Llovet J et al. Hepatocellular carcinoma. Nat Rev Dis Primers. 2016;2:16018. 2: Liver Cancer Study Group of Japan. The 20th follow-up survey of nation-wide research for primary liver cancer 2008-2009. Kanzo. 60(8): 258-293 (2019) 3: Cancer Registry and Statistics. Cancer Information Service, National Cancer Center Japan [Internet; cited September 2020] Available from: https://ganjoho.jp/reg_stat/index.html 4: Giannini G et al. Prognosis of untreated hepatocellular carcinoma. Hepatology. 2015;61(1):184-190.