Updated data showed that Roche's Tecentriq in combination with Avastin shrank tumours in people with unresectable or advanced hepatocellular carcinoma (HCC)

• Data from a Phase Ib study will be presented at the European Society for Medical Oncology (ESMO) 2018 Congress on 21 October
• Tecentriq in combination with Avastin was recently granted Breakthrough Therapy Designation by the US Food and Drug Administration (FDA) as a first-line treatment for people with advanced or metastatic HCC

Roche (SIX: RO, ROG; OTCQX: RHHBY) will today present updated data from a Phase Ib study evaluating Tecentriq^® (atezolizumab) in combination with Avastin^® (bevacizumab) as a treatment for people with unresectable or advanced hepatocellular carcinoma (HCC), the most common form of liver cancer.

The efficacy-evaluable population was comprised of all patients who have received the combination treatment and who have been followed on the study for a minimum of 16 weeks; the median survival follow-up was 7 months. Among the efficacy-evaluable patients, the objective response rate (ORR) was 32% (23 of 73 patients) as assessed by investigator (INV) per RECIST v1.1, 27% (20 of 73 patients) as assessed by independent review facility (IRF) per RECIST v1.1 and 34% (25 of 73 patients) as assessed by IRF per HCC mRECIST.

Complete responses were seen in 1 (1%) patient as assessed by INV per RECIST v1.1, 4 (5%) patients by IRF per RECIST v1.1 and 8 (11%) patients as assessed by IRF per HCC mRECIST. The disease control rate (DCR) was consistent across all forms of assessment, with 77% (56 of 73) of patients assessed by INV per RECIST v1.1 and 75% (55 of 73) as assessed by both IRF per RECIST v1.1 and IRF per HCC mRECIST, experiencing a response or stable disease.

Responses were observed in all assessed patient subgroups, including aetiology, region, baseline alpha-fetoprotein levels and tumour burdens (extrahepatic spread (EHS) and macrovascular invasion (MVI)). Median duration of response (DOR) and overall survival (OS) have not yet been reached.

“We’re pleased to present updated data from our combination of Tecentriq and Avastin at ESMO in unresectable or advanced hepatocellular carcinoma, an aggressive disease that takes the lives of hundreds of thousands of people worldwide each year,” said Sandra Horning, M.D., Roche’s Chief Medical Officer and Head of Global Product Development. “We are encouraged by these results, particularly the durability of response, and we look forward to sharing updated results in the future”.

In the safety-evaluable population (n=103), 27% of patients (28 of 103) experienced Grade 3-4 treatment-related adverse events and 2% of patients (2 of 103) experienced treatment-related Grade 5 adverse events. No new safety signals related to the combination therapy were identified beyond the established safety profiles for the individual medicines.

The late-breaking Phase Ib study data will be presented at the European Society of Medical Oncology (ESMO). Abstract (oral) LBA26 October 21^st CEST 11:00-12:30: Hall A1, Room 17.

In July, the U.S. Food and Drug Administration (FDA) granted Breakthrough Therapy Designation for Tecentriq in combination with Avastin as a first-line treatment for people with advanced or metastatic HCC, based on the totality of data from this ongoing Phase Ib study. Breakthrough Therapy Designation is designed to expedite the development and review of medicines intended to treat serious or life-threatening diseases and to help ensure people can access them as soon as possible. This is one of 23 Breakthrough Therapy Designations for Roche’s portfolio of medicines and the 3^rd for Tecentriq.

Earlier this year, Roche initiated IMbrave150 (NCT03434379), a multicentre, randomised, open-label Phase III study investigating the combination of Tecentriq and Avastin versus sorafenib in people with unresectable or advanced HCC. This study is currently enrolling. Further information about the trial can be found on clinicaltrials.gov.

Efficacy and safety results

a The efficacy-evaluable population was comprised of all patients who have received the combination treatment and who have been followed on the study for a minimum of 16 weeks; the median survival follow-up was 7 months.

b ORR INV per RECIST v1.1 was the primary endpoint in protocol 5, when patients included in this analysis were enrolled.

c Data from 4 patients (6%) not evaluable or missing

d PFS data are very immature, based on a median follow up of 7 months and subject to change.

ORR, objective response rate CR, complete response; PR, partial response; SD, stable disease; PD, progressive disease; DCR, disease control rate; DOR, duration of response; PFS, progression free survival; NR, not reached; +, censored value.

About Hepatocellular Carcinoma (HCC)

Liver cancer is the sixth most common cancer, with over 800,000 new cases diagnosed annually.^[1] It is the fourth most common cause of cancer deaths globally,^[1] and HCC represents approximately 90% of all cases of primary liver cancer.^[2] HCC develops predominantly in those people with cirrhosis due to chronic hepatitis B or C.^[3] Despite the prevalence of HCC, outcomes for unresectable or advanced HCC remain limited, with few systemic therapeutic options,^[4] and a median survival of approximately 6-20 months following diagnosis.^[5]

About the Phase Ib study (NCT02715531)

This Phase Ib, open-label, multicentre study is evaluating the safety and clinical activity of a number of cancer immunotherapy combinations in different solid tumours, including Tecentriq and Avastin in patients with unresectable or advanced HCC (Arm A). Participants in Arm A receive Tecentriq (1200 mg) and Avastin (15 mg/kg) intravenously (IV) every three weeks until loss of clinical benefit or unacceptable toxicity. The primary objectives of Arm A, as of the latest protocol, are to assess the clinical activity, based on ORR assessment by IRF per RECIST v1.1 and to assess the safety and tolerability of the combination. Secondary efficacy endpoints include ORR by INV assessed per RECIST v1.1 and IRF assessed per HCC mRECIST, as well as PFS, DOR and OS. As tumour volume in the liver can also be assessed by discriminating between arterially-enhanced and not vascularised areas, the HCC-specific mRECIST criteria were developed to take this aspect into account and to judge how the liver responds to therapy.
Note: ORR INV per RECIST v1.1 was the primary endpoint in protocol 5, when patients included in this analysis were enrolled.

About IMbrave150 (NCT03434379)

IMbrave150 is a Phase III, multicentre, randomised, open-label study enrolling approximately 480 people with unresectable or advanced HCC 2:1 to receive the combination of Tecentriq and Avastin or sorafenib. Tecentriq will be administered IV, 1200mg on day 1 of each 21-day cycle and Avastin will be administered IV, 15mg/kg on day 1 of each 21-day cycle. Sorafenib will be administered by mouth, 400mg twice per day, on days 1-21 of each 21-day cycle. Participants will receive the combination or sorafenib until unacceptable toxicity or loss of clinical benefit as determined by the investigator. Co-primary endpoints are OS and ORR by IRF per RECIST v1.1. Secondary endpoints include additional efficacy parameters as measured by INV assessed per RECIST v1.1, IRF assessed per RECIST v1.1 and IRF assessed per HCC mRECIST.

About the Tecentriq^® (atezolizumab) and Avastin^® (bevacizumab) combination

There is a strong scientific rationale to support the use of Tecentriq and 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^® (atezolizumab)

Tecentriq is a monoclonal antibody designed to bind with a protein called PD-L1 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 has the potential to be used as a foundational combination partner with cancer immunotherapies, targeted medicines and various chemotherapies across a broad range of cancers.

Tecentriq is already approved in the European Union, United States and more than 70 countries for people with previously treated metastatic NSCLC and for certain types of untreated or previously treated metastatic urothelial carcinoma (mUC).

About Avastin^® (bevacizumab)

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 (metastasize).

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. 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 tenth consecutive year, Roche has been recognised as the most sustainable company 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 2017 employed about 94,000 people worldwide. In 2017, Roche invested CHF 10.4 billion in R&D and posted sales of CHF 53.3 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. World Health Organisation: Globocan 2018 – All cancers factsheet. Available at: http://gco.iarc.fr/today/data/factsheets/cancers/39-All-cancers-fact-sheet.pdf [accessed October 2018]
2. Llovet et al. Hepatocellular carcinoma. Nat Rev Dis Primers. 2016; 14(2): 16018.
3. J. R. Desai et al. Systemic therapy for advanced hepatocellular carcinoma: an update. J Gastrointest Oncol. 2017; 8(2): 243–255.
4. Raza A and Sood GK. Hepatocellular carcinoma review: current treatment, and evidence-based medicine. World J Gastroenterol. 2014; 20(15): 4115-4127.
5. P. Golabi et al. Mortality assessment of patients with hepatocellular carcinoma according to underlying disease and treatment modalities. Medicine. 2017; 96(9): e5904.