Roche announces initiation of two phase III pivotal trials in melanoma based on results of studies combining targeted and immunotherapy treatment approaches; early data presented at the International Congress of the Society for Melanoma Research

• In previously untreated BRAF^V600 mutation-positive metastatic melanoma, combining TECENTRIQ with Cotellic plus Zelboraf was well tolerated with efficacy in the majority of patients, as shown in a phase Ib study
• In BRAF-wild-type and BRAF-mutant metastatic melanoma, TECENTRIQ with Cotellic was well tolerated with promising efficacy in patients, as shown in a separate phase Ib study
• Roche is initiating two phase III studies of these investigational combinations for patients with specific types of metastatic melanoma
• Updated data from the phase III coBRIM study confirms long-term overall survival (OS) benefit for the combination of Cotellic plus Zelboraf vs Zelboraf alone in patients with BRAF^V600 mutation-positive advanced metastatic melanoma

Roche (SIX: RO, ROG; OTCQX: RHHBY) announced results from two early cancer immunotherapy studies at the International Congress of the Society for Melanoma Research (SMR). These early studies of clinical efficacy and safety for combinations including TECENTRIQ® (atezolizumab), Cotellic® (cobimetinib) and Zelboraf^TM (vemurafenib), are advancing the development of new treatment approaches while broadening the understanding of melanoma.  In addition, three-year data from the phase III coBRIM study were presented, confirming the long-term overall survival benefit of Cotellic plus Zelboraf in BRAF^V600 mutation positive advanced or metastatic melanoma.

Safety and efficacy results from 30 patients in a phase Ib study of the combination of TECENTRIQ, an anti-PD-L1 monoclonal antibody, with Cotellic, a MEK inhibitor, plus Zelboraf, a BRAF inhibitor, in previously untreated patients with BRAF^V600 mutation-positive metastatic melanoma, were presented. Median safety follow-up was 3.9 months (range 0.7-16.8). Grade 3-4 adverse events (AEs) were seen in 40 percent of patients treated with the triple combination; all resolved after appropriate interventions. No unexpected AEs, Grade 5 AEs or TECENTRIQ-related serious AEs occurred. Out of 29 evaluable patients for efficacy, responses were seen in 24 patients (83 percent) with 3 complete responses and 21 partial responses; the majority of patients continued to respond at the time of data cut-off (median follow up of 5.6 months).

Results were also presented from a phase Ib study of TECENTRIQ with Cotellic, including efficacy and safety data for 22 patients with metastatic melanoma (2 ocular, 20 non-ocular with 10 each BRAF-mutant and wild-type). Patients had received a median of 1 prior therapy for melanoma (range 0-8), but had not received prior anti-PD-1/PD-L1 therapy. Median safety follow-up was 14.0 months (range 2.4-20.2 months). Grade 3-4 AEs occurred in 59 percent of patients, no treatment-related Grade 5 AEs were reported; all AEs were manageable. Among the 20 patients with non-ocular metastatic melanoma the objective response rate (ORR) was 45 percent (50 percent in BRAF wild-type and 40 percent in BRAF-mutant patients). The median progression-free survival (PFS) was 12 months in the non-ocular melanoma patients (15.7 months in BRAF wild-type and 11.9 months in BRAF-mutant patients).

"We are encouraged by these early results which demonstrate a high proportion of people responded to these investigational combination therapies,” said Sandra Horning, MD, Roche’s Chief Medical Officer and Head of Global Product Development.  “The results suggest that the combination of TECENTRIQ with our BRAF and MEK targeted agents may extend the established benefits of the approved monotherapy and combination approaches of these medicines.”

Based on the promising results of these Phase Ib studies, Roche plans to initiate two Phase III studies of these investigational combinations for patients with metastatic melanoma.  These pivotal trials will study TECENTRIQ with Cotellic plus Zelboraf in treatment-naïve, BRAF-mutant metastatic melanoma and TECENTRIQ with Cotellic in treatment-naïve, BRAF wild-type metastatic melanoma.

Additionally, updated OS data from the phase III coBRIM study of Cotellic plus Zelboraf have demonstrated the continuing benefit across all patient subgroups of the combination therapy vs Zelboraf alone, in patients with BRAF^V600-mutation positive unresectable locally advanced metastatic melanoma. The percentage of patients alive at three years was 37.4 percent for people treated with Cotellic plus Zelboraf vs 31.1 percent for patients treated with placebo plus Zelboraf. Median OS was 22.5 months for Cotellic plus Zelboraf vs 17.4 months for Zelboraf alone.

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About Cotellic and Zelboraf in combination

Zelboraf was the first approved treatment for patients with unresectable or metastatic melanoma with BRAF V600 mutation as detected by a validated test, such as Roche’s cobas 4800 BRAF Mutation Test. Zelboraf is not indicated for use in patients with wild-type BRAF melanoma.  Cotellic (cobimetinib) is designed to selectively block the activity of MEK, one of a series of proteins inside cells that make up the MAPK signaling pathway that helps regulate cell division and survival. In the majority of patients, resistance to BRAF-inhibitor monotherapy will eventually occur through re-activation of the MAPK pathway via MEK.  Cotellic was developed to overcome resistance to BRAF-inhibition and prevent re-activation of the pathway.  Cotellic binds to MEK, while Zelboraf binds to mutant BRAF, to interrupt abnormal signalling that can cause tumours to grow.

Cotellic is also being investigated in combination with several investigational medicines, including immunotherapy, in several tumour types such as non-small cell lung cancer and colorectal cancer. Cotellic was discovered by Exelixis Inc. and is being developed by Roche in collaboration with Exelixis.

About melanoma

Melanoma is less common, but more aggressive and deadlier than other forms of skin cancer. A V600 mutation of the BRAF protein occurs in approximately half of melanomas, and should therefore be tested to identify the best treatment option. When melanoma is diagnosed early, it is generally a curable disease, but most people with advanced melanoma have a poor prognosis. More than 232,000 people worldwide are currently diagnosed with melanoma each year. In recent years, there have been significant advances in treatment for metastatic melanoma, and people with the disease have more options. However, it continues to be a serious health issue with a high unmet need and a steadily increasing incidence over the past 30 years.

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 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.

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 eight years in a row by the Dow Jones Sustainability Indices.

The Roche Group, headquartered in Basel, Switzerland, is active in over 100 countries and in 2015 employed more than 91,700 people worldwide. In 2015, Roche invested CHF 9.3 billion in R&D and posted sales of CHF 48.1 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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