Roche : cancer immunotherapy Tecentriq (atezolizumab) shrank tumours in people with previously untreated advanced bladder cancer

Basel, 5 June 2016

• New survival results also reported from study group with previously treated advanced bladder cancer
• Tecentriq is the first and only cancer immunotherapy FDA approved to treat bladder cancer

Roche (SIX: RO, ROG; OTCQX: RHHBY), today announced that in a Phase II study, IMvigor210, Tecentriq® (atezolizumab) shrank tumours (objective response rate, ORR) in 24 percent (n=28) of people with locally advanced or metastatic urothelial carcinoma (mUC) who have not received a prior treatment (first-line) and who were ineligible for cisplatin-based chemotherapy. Of those people who responded, 75 percent (n=21) continued to respond to treatment and the median duration of response (mDOR) had not been reached at the time of analysis. Seven percent (n=8) of all people in the study achieved a complete response (CR). The median overall survival (OS) was 14.8 months. The safety profile of Tecentriq was consistent with that observed in earlier analyses of the study, as well as in other studies of Tecentriq as a monotherapy. Full results will be presented in an oral session at the 52nd Annual Meeting of the American Society of Clinical Oncology (ASCO) and highlighted as part of ASCO's official press programme.

'These Tecentriq results are highly encouraging because about half of all people with this type of bladder cancer are not able to tolerate a cisplatin-based chemotherapy, and alternative treatments bring very limited duration of response,' said Sandra Horning, M.D., Chief Medical Officer and Head of Global Product Development. 'We are particularly pleased that the majority of people who responded to Tecentriq continued to respond at the time of analysis.'

About the IMvigor210 study

IMvigor210 is an open-label, multicentre, single-arm phase II study that evaluated the safety and efficacy of Tecentriq in people with locally advanced or mUC, regardless of PD-L1 expression. People in the study were enrolled into one of two cohorts. Cohort 1 consisted of people who had received no prior therapies for locally advanced or mUC and who were ineligible for first-line cisplatin-based chemotherapy. Cohort 2 included people whose disease progressed during or following previous treatment with a platinum-based chemotherapy regimen (second-line or later). The primary endpoint of the study was ORR. Secondary endpoints included duration of response (DOR), overall survival (OS), progression-free survival (PFS) and safety. PD-L1 (programmed death-ligand 1) expression was assessed using an immunohistochemistry (IHC) test developed by Roche Tissue Diagnostics.

Full results from IMvigor210 Cohort 1 will be presented by Arjun Balar, M.D., Director of Genitourinary Medical Oncology at Perlmutter Cancer Center, New York University Langone Medical Center, New York, N.Y. (Abstract #LBA4500, Sunday, June 5, 8:00 - 8:12 A.M. CDT).

Updated data from IMvigor 210 Cohort 1 (previously untreated, first-line) showed:

• ORR was 24 percent (n=28) (95 percent CI; 16, 32)
• 7 percent (n=8) of all people in the study cohort achieved a complete response (CR)
• Median DOR was not reached with a median follow-up duration of 14.4 months; 75 percent of responses (n=21) were ongoing at the time of analysis
• Median OS was 14.8 months (95 percent CI; 10.1, not estimable), and the 12 month landmark OS was 57 percent

Fifteen percent of people receiving Tecentriq experienced severe (Grade 3 and 4) treatment-related adverse events. Six percent of people experienced an adverse event leading to treatment discontinuation, and 35 percent had an adverse event leading to dose interruption. Six percent of people experienced an adverse event leading to treatment discontinuation, and 35 percent had an adverse event leading to dose interruption. Treatment-related adverse events (all grades) occurred in 66 percent of people. One Grade 5 treatment-related adverse event occurred (sepsis, or blood infection). Six percent of people had Grade 3-4 immune-mediated adverse events.

Updated results from IMvigor 210 Cohort 2, the trial upon which Tecentriq received U.S. Food and Drug Administration accelerated approval for the treatment of people with locally advanced or mUC who have disease progression during or following platinum-based chemotherapy, or whose disease has worsened within 12 months of receiving platinum-based chemotherapy before surgery (neoadjuvant) or after surgery (adjuvant), will be presented by Robert Dreicer, Associate Director of Clinical Research, Hematology and Oncology, University of Virginia School of Medicine, Charlottesville, Va. in an oral session (Abstract #4515, Sunday, June 5, 8:36 - 8:48 A.M. CDT).

Updated data from IMvigor 210 Cohort 2 (previously treated with platinum-based chemotherapy) showed:

• An ORR of 16 percent (n=49) (95 percent CI; 12, 20)
• 7 percent (n=21) of people achieved a CR
• Median DOR was not reached with a median follow-up duration of 17.5 months; 71 percent of responses were ongoing at the time of analysis
• Median OS was 7.9 months (95 percent CI, 7, 9), and he 12 month landmark OS was 37 percent

Seventeen percent of people receiving Tecentriq experienced severe (Grade 3 and 4) treatment-related adverse events. Three percent of people experienced an adverse event leading to treatment discontinuation, and 31 percent had an adverse event leading to dose interruption. Treatment-related adverse events (all grades) occurred in 70 percent of people. Three Grade 5 adverse events occurred: intestinal obstruction, sepsis (blood infection) and bleeding in the brain (cerebral hemorrhage).

About Tecentriq (atezolizumab)

Tecentriq is a monoclonal antibody designed to target and bind to a protein called PD-L1 (programmed death ligand-1), which is expressed on tumour cells and tumour-infiltrating immune cells. PD-L1 interacts with PD-1 and B7.1, both found on the surface of T cells, causing inhibition of T cells. By blocking this interaction, Tecentriq may enable the activation of T cells, restoring their ability to effectively detect and attack tumour cells.

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.

About personalised cancer immunotherapy

The aim of personalised cancer immunotherapy (PCI) is to provide individual patients with treatment options that are tailored to their specific needs. The Roche PCI research and development programme comprises more than 20 investigational candidates, nine of which are in clinical trials. All studies include the prospective evaluation of biomarkers to determine which people may be appropriate candidates for Roche medicines. In the case of Tecentriq, PCI begins with the PD-L1 (programmed death ligand-1) IHC assay based on the SP142 antibody developed by Roche Tissue Diagnostics. The goal of PD-L1 as a biomarker is to identify those people most likely to experience clinical benefit with Tecentriq as a single agent versus those who may benefit more from combination approaches; the purpose is to inform treatment strategies which will give the greatest number of patients a chance for transformative benefit. The ability to combine Tecentriq with multiple chemotherapies may provide new treatment options to people across a broad range of tumours regardless of their level of PD-L1 expression.

PCI is an essential component of how Roche delivers on the broader commitment to personalised healthcare.

About Roche

Roche is a global pioneer in pharmaceuticals and diagnostics focused on advancing science to improve people's lives.

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. The ombined 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.

Founded in 1896, Roche continues to search for better ways to prevent, diagnose and treat diseases and make a sustainable contribution to society. Twenty-nine 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. Roche has been recognised as the Group Leader in sustainability within the Pharmaceuticals, Biotechnology & Life Sciences Industry seven years in a row by the Dow Jones Sustainability Indices.

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