Roche : to present new data on Tecentriq in combination with Avastin that shows improvement in overall survival for Chinese patients with the most common form of liver cancer

Roche to present new data on Tecentriq in combination with Avastin that shows improvement in overall survival for Chinese patients with the most common form of liver cancer

• Overall survival outcomes for Chinese patients treated with the combination of Tecentriq and Avastin are consistent with the overall survival reported for the global patient population of the IMbrave150 study
• IMbrave150 is the first cancer immunotherapy study to show an improvement in overall survival and progression-free survival in people with unresectable hepatocellular carcinoma compared with sorafenib
• Results will be presented tomorrow at the Liver Cancer Summit 2020 (European Association for the Study of the Liver [EASL]), 6-8 February 2020

Basel, 7 February 2020 - Roche (SIX: RO, ROG; OTCQX: RHHBY) today announced that additional data will be presented from a cohort of Chinese patients in the Phase III IMbrave150 study that evaluated Tecentriq® (atezolizumab) in combination with Avastin® (bevacizumab) as a treatment for people with unresectable hepatocellular carcinoma (HCC) who have not received prior systemic therapy.

Data from 194 Chinese patients who took part in the IMbrave150 study were consistent with the global results, that showed a statistically significant and clinically meaningful improvement in overall survival (OS) and progression-free survival (PFS) compared with standard-of-care sorafenib.

Among Chinese patients, Tecentriq in combination with Avastin reduced the risk of death (OS) by 56% (hazard ratio [HR]=0.44; 95% CI: 0.25-0.76) and reduced the risk of disease worsening or death (PFS) by 40% (HR=0.60; 95% CI: 0.40-0.90), compared with sorafenib. Tecentriq and Avastin were generally well-tolerated with manageable toxicities, and the safety profile was consistent with the known safety profiles of the individual medicines and with the underlying disease.

'Almost half of all cases of hepatocellular carcinoma globally are found in China, so it is extremely encouraging that Chinese patients treated with Tecentriq and Avastin had substantially longer survival outcomes, as compared with the current standard of care in China', said Levi Garraway, M.D., Ph.D, Roche's Chief Medical Officer and Head of Global Product Development. 'We are working closely with the China National Medical Products Administration (NMPA), who recently accepted our supplemental Biologics License Application (sBLA) for the combination, along with global health authorities in the hope of bringing this treatment option to patients as soon as possible.'

These data will be presented in the plenary session entitled 'Round table focus on HCC and transplantation' at the Liver Cancer Summit 2020, on 8 February at 08:00 am CET.

Every year, more than 750,000 people worldwide are diagnosed with HCC, the most common form of liver cancer - with the majority of cases in Asia and almost half of all cases in China. Elsewhere, incidence of liver cancer is on the rise across Europe and the US, with the number of liver cancer cases in the US more than tripling since 1980.

Roche has an extensive development programme for Tecentriq, including multiple ongoing and planned Phase III studies, across several types of lung, genitourinary, skin, breast, gastrointestinal, gynaecological, and head and neck cancers. This includes studies evaluating Tecentriq both alone and in combination with other medicines.
About the IMbrave150 study
IMbrave150 is a global Phase III, multicentre, open-label study of 501 people with unresectable HCC who have not received prior systemic therapy. People were randomised 2:1 to receive the combination of Tecentriq and Avastin or sorafenib. Of 194 Chinese patients (137 from the IMbrave150 global study and 57 from a China extension cohort), 133 were randomised to receive Tecentriq and Avastin and 61 to sorafenib. Tecentriq was administered intravenously (IV), 1200 mg on day 1 of each 21-day cycle, and Avastin was administered IV, 15 mg/kg on day 1 of each 21-day cycle. Sorafenib was administered by mouth, 400 mg twice per day, on days 1-21 of each 21-day cycle. People received the combination or the control arm treatment until unacceptable toxicity or loss of clinical benefit, as determined by the investigator. The co-primary endpoints were OS and PFS by independent review facility (IRF) per Response Evaluation Criteria in Solid Tumours Version 1.1 (RECIST v1.1). Additional study endpoints included overall response rate (ORR), PFS and duration of response (DoR), as measured by RECIST v1.1 (investigator-assessed [INV] and IRF) and HCC mRECIST (IRF), as well as patient-reported outcomes (including time to deterioration of patient-reported quality of life), safety and pharmacokinetics.

Key efficacy endpoint results for OS and PFS (co-primary endpoints) in Chinese patients are shown below:

	Tecentriq + Avastin (n=133)	Sorafenib (n=61)
Median OS, months (95% CI)	NE (13.5-NE)	11.4 (6.7-NE)
OS, HR (95% CI)	0.44 (0.25-0.76)
Median PFS, months (95% CI)	5.7 (4.2-8.3)	3.2 (2.6-4.8)
PFS, HR (95% CI)	0.60 (0.40-0.90)

NE, not estimable; median follow-up 7.2 months (Tecentriq and Avastin) and 5.6 months (sorafenib); PFS measured as per IRF RECIST v1.1. No formal statistical testing was conducted in the Chinese subpopulation.

Grade 3-4 adverse events (AEs) occurred in 59% of people receiving Tecentriq and Avastin and 47% of people receiving sorafenib. Grade 5 AEs occurred in 2% and 3% of people, respectively.

Key efficacy endpoint results for OS and PFS (co-primary endpoints) for the global population are shown below:

	Tecentriq + Avastin (n=336)	Sorafenib (n=165)
Median OS (months) (95% CI)	NE	13.2 (10.4-NE)
OS, HR (95% CI)	0.58 (0.42-0.79)
Log rank p-value	0.0006
Median PFS (months) (95% CI)	6.8 (5.7-8.3)	4.3 (4.0-5.6)
PFS, HR (95% CI)	0.59 (0.47-0.76)
Log rank p-value	<0.0001

NE, not estimable; median follow-up 8.6 months; PFS measured as per IRF RECIST v1.1.
Grade 3-4 adverse events (AEs) occurred in 57% of people receiving Tecentriq and Avastin and 55% of people receiving sorafenib. Grade 5 AEs occurred in 5% and 6% of people, respectively.

About hepatocellular carcinoma
HCC is an aggressive cancer with limited treatment options and is a major cause of cancer deaths worldwide.^[1] Every year, more than 750,000 people worldwide are diagnosed with HCC,^[1],[2] with the majority of cases in Asia and almost half of all cases in China.^[2],[3] In the US, the number of liver cancer cases have more than tripled since 1980 and HCC represents the fastest-rising cause of cancer-related death, while in Europe, liver cancer is also on the rise.^[4-6] 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 poor, with few systemic therapeutic options and a 1-year survival rate of less than 50% following diagnosis.^[7]
About the Tecentriq and Avastin combination
There is a strong scientific rationale to support the use of Tecentriq plus Avastin in combination. The Tecentriq and Avastin regimen may enhance the potential of the immune system to combat a broad range of cancers. Avastin, in addition to its established anti-angiogenic effects, may further enhance Tecentriq's ability to restore anti-cancer immunity, by inhibiting vascular endothelial growth factor (VEGF)-related immunosuppression, promoting T-cell tumour infiltration and enabling priming and activation of T-cell responses against tumour antigens.

About Tecentriq
Tecentriq is a monoclonal antibody designed to bind with a protein called PD-L1, which is expressed on tumour cells and tumour-infiltrating immune cells, blocking its interactions with both PD-1 and B7.1 receptors. By inhibiting PD-L1, Tecentriq may enable the activation of T-cells. Tecentriq is a cancer immunotherapy that has the potential to be used as a foundational combination partner with other immunotherapies, targeted medicines and various chemotherapies across a broad range of cancers. The development of Tecentriq and its clinical programme is based on our greater understanding of how the immune system interacts with tumours and how harnessing a person's immune system combats cancer more effectively.

Tecentriq is approved in the US, EU and countries around the world, either alone or in combination with targeted therapies and/or chemotherapies in various forms of non-small cell and small cell lung cancer, certain types of metastatic urothelial cancer, and in PD-L1-positive metastatic triple-negative breast cancer.

About Avastin
Avastin is a prescription-only medicine that is a solution for intravenous infusion. It is a biologic antibody designed to specifically bind to a protein called VEGF that plays an important role throughout the lifecycle of the tumour to develop and maintain blood vessels, a process known as angiogenesis. Avastin is designed to interfere with the tumour blood supply by directly binding to the VEGF protein to prevent interactions with receptors on blood vessel cells. The tumour blood supply is thought to be critical to a tumour's ability to grow and spread in the body (metastasise).

About Roche in cancer immunotherapy
For more than 50 years, Roche has been developing medicines with the goal to redefine treatment in oncology. Today, we're investing more than ever in our effort to bring innovative treatment options that help a person's own immune system fight cancer.

By applying our seminal research in immune tumour profiling within the framework of the Roche-devised cancer immunity cycle, we are accelerating and expanding the transformative benefits with Tecentriq to a greater number of people living with cancer. Our cancer immunotherapy development programme takes a comprehensive approach in pursuing the goal of restoring cancer immunity to improve outcomes for patients.

To learn more about the Roche approach to cancer immunotherapy please follow this link:
http://www.roche.com/research_and_development/what_we_are_working_on/oncology/cancer-immunotherapy.htm

About Roche
Roche is a global pioneer in pharmaceuticals and diagnostics focused on advancing science to improve people's lives. The combined strengths of pharmaceuticals and diagnostics under one roof have made Roche the leader in personalised healthcare - a strategy that aims to fit the right treatment to each patient in the best way possible.

Roche is the world's largest biotech company, with truly differentiated medicines in oncology, immunology, infectious diseases, ophthalmology and diseases of the central nervous system. Roche is also the world leader in in vitro diagnostics and tissue-based cancer diagnostics, and a frontrunner in diabetes management.

Founded in 1896, Roche continues to search for better ways to prevent, diagnose and treat diseases and make a sustainable contribution to society. The company also aims to improve patient access to medical innovations by working with all relevant stakeholders. More than thirty medicines developed by Roche are included in the World Health Organization Model Lists of Essential Medicines, among them life-saving antibiotics, antimalarials and cancer medicines. Moreover, for the eleventh consecutive year, Roche has been recognised as one of the most sustainable companies in the Pharmaceuticals Industry by the Dow Jones Sustainability Indices (DJSI).

The Roche Group, headquartered in Basel, Switzerland, is active in over 100 countries and in 2019 employed about 98,000 people worldwide. In 2019, Roche invested CHF 11.7 billion in R&D and posted sales of CHF 61.5 billion. Genentech, in the United States, is a wholly owned member of the Roche Group. Roche is the majority shareholder in Chugai Pharmaceutical, Japan. For more information, please visit www.roche.com.
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References
[1] Llovet JM et al. Hepatocellular carcinoma. Nat Rev Dis Primers. 2016;2:16018.
[2] World Health Organization: Globocan 2018 - Liver cancer factsheet. [Internet; cited 2020 Jan] Available from: http://gco.iarc.fr/today/data/factsheets/cancers/11-Liver-fact-sheet.pdf.
[3] World Health Organization: Globocan 2018 - China factsheet. [Internet; cited 2020 Jan] Available from: http://gco.iarc.fr/today/data/factsheets/populations/160-china-fact-sheets.pdf.
[4] American Cancer Society: Key statistics about liver cancer. [Internet; cited 2020 Jan] Available from: https://www.cancer.org/cancer/liver-cancer/about/what-is-key-statistics.html.
[5] Rawla P et al. Update in global trends and aetiology of hepatocellular carcinoma. Contemp Oncol (Pozn). 2018;22(3):141-150.
[6] Pimpin L et al. Burden of liver disease in Europe: Epidemiology and analysis of risk factors to identify prevention policies. J Hepatol 2018;69(3):718-735.
[7] Giannini EG et al. Prognosis of untreated hepatocellular carcinoma. Hepatology. 2015;61(1):184-190.