Media Release Basel, 8 January 2016 Roche presents updated results for investigational cancer immunotherapy atezolizumab in advanced bladder cancer Higher expression of PD-L1 (programmed death-ligand 1) was associated with higher response rates, however low levels of PD-L1 expression did not preclude response Responses were ongoing in the majority of people Complete Responses (CR) were observed regardless of levels of PD-L1 expression Roche (SIX: RO, ROG; OTCQX: RHHBY) today announced updated results from the pivotal phase II study, IMvigor 210, of the investigational cancer immunotherapy atezolizumab (MPDL3280A) in people with locally advanced or metastatic urothelial carcinoma (muc). Median overall survival (mos) in this heavily pre-treated population was 11.4 months [95% CI: 9.0, NE] in people with higher levels of PD-L1 expression, and 7.9 months [95% CI: 6.6, 9.3] in the overall study population. The study also showed that 84% (n=38/45) of people who responded to atezolizumab continued to respond regardless of their PD-L1 status, when the results were assessed with longer median follow-up of 11.7 months. Median duration of response has not yet been reached. Atezolizumab was well tolerated and adverse events were consistent with those observed in previous updates. These data were presented at the 2016 Genitourinary Cancers Symposium of the American Society of Clinical Oncology (ASCO GU). 1 It is encouraging to see that the majority of people with advanced bladder cancer who responded to atezolizumab maintained their response with longer follow up, said Sandra Horning, MD, Chief Medical Officer and Head of Global Product Development. We are looking forward to sharing these results with the US FDA and other health authorities in the hope that we may bring atezolizumab to treating physicians and their patients as soon as possible. Roche is planning to submit these data imminently to Global health authorities and the U.S. Food and Drug Administration (FDA) under Breakthrough Therapy designation. This designation is designed to expedite the development and review of medicines that may demonstrate substantial improvement over existing therapies for serious diseases. F. Hoffmann-La Roche Ltd 4070 Basel Switzerland Group Communications Roche Group Media Relations Tel. +41 61 688 88 88 Fax +41 61 688 27 75 www.roche.com 1/5
About the IMvigor 210 study IMvigor 210 is an open-label, multicentre, single-arm phase II study that evaluated the safety and efficacy of atezolizumab 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 comprised those who had received no prior therapies for locally advanced or muc, but who were ineligible for first-line cisplatin-based therapy. The results for this cohort are not yet mature. Cohort 2, for which updated results were announced today, included people whose disease had progressed during or following previous treatment with a platinum-based chemotherapy regimen(heavily pretreated), 41 percent of people in the study had 2 or more treatments in the metastatic setting. People received a 1200-mg intravenous dose of atezolizumab on day 1 of 21-day cycles until progressive disease (Cohort 1) or loss of clinical benefit (Cohort 2). Co-primary endpoints of the study included confirmed RECIST v1.1 ORR per central IRF and investigatorassessed modified RECIST ORR. Secondary endpoints included duration of response, overall survival, progression-free survival and safety. People were selected by histology, prior lines of therapy and PD-L1 expression on tumour-infiltrating immune cells (IC), using an investigational immunohistochemistry test that is being developed by Roche Tissue Diagnostics. IMvigor 210 cohort 2 study results: (median follow-up of 11.7 months: range, 0.2+ to 15.2 mo) Study group measurable expression IC 2/3 (medium and high) IC 1/2/3 (any expression) ITT (Intent to Treat), all patients Number of patients 100 207 310 ORR* (Co-primary endpoints) ORR, % Confirmed RECIST v.1.1 ORR per IRF 26 (CI: 18, 36) 18 (CI: 13, 24) 15 (CI: 11, 19) Complete Response 11% 6% 5% DoR (IRF-assessed; RECIST v1.1; secondary endpoint) Median DoR, months Not reached in any PD-L1 subgroup ( 2.0*, 13.7* months, *censored values) PFS (IRF-assessed; RECIST v1.1) (Secondary Endpoint) Median PFS, months (95% CI) (CI:, 4.1) (CI: 2.0, ) (CI:, ) 6-month PFS 30% 23% 21% 2/5
(CI: 21, 39) (CI: 18, 29) (CI: 17, 26) OS (secondary endpoint) Median OS, months 11.4 (CI: 9.0, NE) 8.8 (CI: 7.1, 10.6) 7.9 (CI: 6.6, 9.3) 12-month OS 48% (CI: 38, 58) 39% (CI: 32, 46) 36% (CI: 30, 41) Safety (n=310) Atezolizumab was well tolerated with no treatment-related deaths, a low rate of treatmentrelated Grade 3 4 toxicities and no treatment-related renal toxicity or related Grade 5 AEs o 16% of people experienced Grade 3 4 treatment-related AEs and 5% experienced a Grade 3 4 immune-related AE o The most common Grade 3 4 treatment-related AEs were fatigue (2%), decreased appetite, anaemia, inflammation of the lung wall (pneumonitis), hypertension and hypotension, colitis, arthralgia, dyspnoea, enzymes in the blood (ALT increase) (all 1%) *ORR was assessed by central review (RECIST v1.1) and by investigators using modified RECIST (co-primary endpoints). IC: tumour-infiltrating immune cell; ITT: intent to treat; CI: confidence interval; NE: not estimable; DoR: duration of response; CR: complete response; ORR: objective response rate; PFS: progression-free survival; OS: overall survival; AE: adverse events In addition to IMvigor 210, Roche has an ongoing randomised phase III study, IMvigor 211, comparing atezolizumab with standard-of-care chemotherapy in people who have muc that worsened after initial treatment. All studies include the evaluation of a companion test developed by Roche Tissue Diagnostics to determine PD-L1 status. About metastatic urothelial cancer Metastatic urothelial cancer is associated with a poor prognosis and limited treatment options. It is a disease that has seen no major advancements for nearly 30 years. Urothelial cancer is the ninth most common cancer worldwide, with 430,000 new cases diagnosed in 2012, and it results in approximately 145,000 deaths globally each year. Men are three times more likely to suffer from urothelial cancer compared with women, and it is also three times more common in developed countries than in less developed countries. About atezolizumab Atezolizumab (also known as MPDL3280A) is an investigational monoclonal antibody designed to target and bind to a protein called PD-L1, which is expressed on TCs and tumour-infiltrating ICs. 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 3/5
interaction, atezolizumab 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 30 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. Our PCI research and development programme comprises more than 20 investigational candidates, eight of which are in clinical trials. All studies include the prospective evaluation of biomarkers to determine which people may be appropriate candidates for our medicines. In the case of atezolizumab (also known as MPDL3280A), 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 atezolizumab as a single agent and which people may be appropriate candidates for combination therapies; the purpose is not to exclude patients from atezolizumab therapy, but rather to enable the design of combinations that will provide the greatest chance for transformative responses. The ability to combine atezolizumab with multiple chemotherapies may provide new treatment options to people across a broad range of tumours regardless of their level of PD-L1 expression. About Roche Headquartered in Basel, Switzerland, Roche is a leader in research-focused healthcare with combined strengths in pharmaceuticals and diagnostics. Roche is the world s largest biotech company, with truly differentiated medicines in oncology, immunology, infectious diseases, ophthalmology and neuroscience. Roche is also the world leader in in vitro diagnostics and tissue-based cancer diagnostics, and a frontrunner in diabetes management. Roche s personalised healthcare strategy aims at providing medicines and diagnostics that enable tangible improvements in the health, quality of life and survival of patients. Founded in 1896, Roche has been making important contributions to global health for more than a century. Twentynine medicines developed by Roche are included in the World Health Organization Model Lists of Essential Medicines, among them life-saving antibiotics, antimalarials and chemotherapy. 4/5
In 2014, the Roche Group employed 88,500 people worldwide, invested 8.9 billion Swiss francs in R&D and posted sales of 47.5 billion Swiss francs. 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. All trademarks used or mentioned in this release are protected by law. Find out more about Roche in oncology here: www.roche.com/research_and_development/what_we_are_working_on/oncology.htm Roche Group Media Relations Phone: +41-61 688 8888 / Email: roche.mediarelations@roche.com Nicolas Dunant (Head) Ulrike Engels-Lange - Nicole Rüppel Claudia Schmitt Anja von Treskow Reference 1. Hoffman-Censits J., et al. IMvigor 210, a phase 2 trial of atezolizumab (MPDL3280A) in platinum-treated locally-advanced or metastatic urothelial carcinoma (muc) #355. Friday, 8 January 2016, [0755 0930], San Francisco, CA, USA. 5/5