Roche : showcases three distinct combinations for cancer immunotherapy treatment across a broad range of cancers

Basel, 4 June 2016

Roche showcases three distinct combinations for cancer immunotherapy treatment across a broad range of cancers

• Early data for Tecentriq® (atezolizumab) in combination with targeted therapy Cotellic® (cobimetinib) for people with advanced colorectal cancer (mCRC) was well tolerated with responses observed regardless of Programmed Death Ligand-1 (PD-L1) expression
• Updated data of Tecentriq in combination with Abraxane chemotherapy for people with advanced triple-negative breast cancer (mTNBC) shows responses occurring across all lines of therapy including some durable responses
• First data from dose finding study of Tecentriq in combination with anti-OX40 treatment (MOXR0916), shows a favourable safety profile and evidence of immune activation

Roche (SIX: RO, ROG; OTCQX: RHHBY) is presenting data from across its cancer immunotherapy pipeline highlighting its multipronged combination approach to cancer immunotherapy treatment. The first combination trial evaluated Tecentriq with targeted therapy Cotellic in a phase Ib study in people with mCRC who had been heavily pretreated. The study demonstrated a tolerable safety profile with an Overall Response Rate (ORR) of 17 percent (n=4). All responders had the KRAS gene mutation, and responses were observed irrespective of Microsatellite Instability (MSI) status. Responses were ongoing in two out of four people at the time of data analysis. The second evaluated a combination with Tecentriq and Abraxane chemotherapy in a phase Ib study for people with mTNBC. The results showed that the safety profile was similar to that previously seen with Tecentriq or Abraxane chemotherapy alone. An ORR of 38% (n=32) was observed across all lines of therapy. The final combination being presented are dose-escalation results from the ongoing phase Ib study of the investigational Roche cancer immunotherapy molecule (MOXR0916, anti-OX40) and Tecentriq. The data showed a favourable safety profile and evidence of immune activation, supporting the continuation of further investigation into the potential benefits this combination could bring to patients.

'Combinations based on a deep understanding of the science are a central component of our cancer immunotherapy development strategy.'' said Sandra Horning, MD, Roche's Chief Medical Officer and Head of Global Product Development. 'We believe we may be able to bring the full potential of treatments such as Tecentriq to a greater number of people by exploiting different mechanisms of action in combination, such as with chemotherapy, targeted treatments and other immunotherapy agents.''

Further information on Roche's contribution to the ASCO 2016 scientific programme, the company's wider progress in cancer care and key data being presented at the conference will be featured at a Roche investor briefing on Sunday 5 June between 6pm - 8pm CDT. This event is independently organised by Roche and is open to analysts attending the ASCO 2016 Annual Meeting. To register for the Roche investor briefing, please use the following link:
http://www.roche.com/investors/updates/inv-update-2016-04-27.htm

To learn more about Roche's personalised cancer immunotherapy programme and Roche's contribution to ASCO 2016, please follow Roche on Twitter via @Roche. You can keep up to date with ASCO 2016 Annual Meeting news and updates by using the hashtag #ASCO16.

About the phase Ib combination study of Tecentriq with Cotellic in advanced CRC

Overview and study design

• A phase Ib, open-label, multicentre study designed to assess the safety, tolerability and pharmacokinetics of co-administration of intravenous dosing of Tecentriq and oral dosing of Cotellic in participants with metastatic or locally advanced cancer for which standard therapies have been exhausted
• The primary endpoints of the study were safety and tolerability with secondary endpoints including ORR confirmed by RECIST v1.1
• 23 CRC (22 KRAS mutant, one wild type) patients were enrolled during escalation and expansion
• Cobimetinib was escalated from 20 mg to 60 mg daily (21 days on/7 days off) and combined with Tecentriq 800 mg IV q2w

About the phase Ib combination study of Tecentriq with Abraxne in mTNBC

Overview and study design

• GP28328 (NCT01633970) was a multi-centre, multi-arm study evaluating Tecentriq in combination with Abraxane chemotherapy. Arm F consisted of patients with TNBC (up to 3 prior lines of chemotherapy were allowed)
• -- The primary endpoint was safety and tolerability
• -- Secondary endpoints included efficacy per RECIST v1.1 criteria (best overall response, objective response rate, duration of response, progression-free survival) and immune-related response criteria (irRC), pharmacokinetics and biomarker analyses

About the phase Ib study of MOXR0916 (OX40) and Tecentriq in advanced solid tumours

Overview and study design

• A phase Ib, open-label, multicentre study evaluating the safety and pharmacokinetics of MOXR0916 and Tecentriq in patients with locally advanced or metastatic solid tumours
• The primary endpoint of the study is safety and tolerability,
• A 3+3 dose-escalation was conducted with a 21-day window to evaluate dose-limiting toxicity
• -- Escalating doses of MOXR0916 in combination with a fixed 1200 mg dose of Tecentriq were administered every three weeks (q3w)
• An expansion cohort to enable immune profiling of serial tumour biopsies was also enrolled
• 28 patients were treated in eight dose-escalation cohorts (MOXR0916 dose levels 0.8-1200 mg) and 23 additional patients were treated in the serial biopsy cohort
• -- The median number of prior therapies for metastatic disease was two (range 0-7) and nine patients had received prior PD-1/PD-L1 antibodies

Results:

• No dose-limiting toxicities, Grade 4/5 adverse events (AEs) attributed to study treatment or related AEs leading to treatment discontinuation were reported
• -- The majority of treatment-related AEs were Grade 1 in severity; one related Grade 3 event (pneumonitis responsive to corticosteroids) was reported
• Evidence of immune activation, including upregulation of PD-L1, was observed in paired tumour biopsies from some patients, including patients whose immediate prior therapy was anti-PD-1

The regimen selected for dose expansion is MOXR0916 300 mg + Tecentriq 1200 mg q3w. Evaluation of efficacy is ongoing in expansion cohorts for patients with melanoma, RCC, NSCLC, urothelial carcinoma, and TNBC.

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 Tecentriq (atezolizumab)

Tecentriq is a monoclonal antibody designed to bind with a protein called PD-L1. Tecentriq is designed to directly bind to PD-L1 expressed on tumour cells and tumour-infiltrating immune cells, blocking its interactions with PD-1 and B7.1 receptors. By inhibiting PD-L1, Tecentriq may enable the activation of T cells. Tecentriq may also affect normal cells.

About MOXR0916 (anti-OX40)

MOXR0916 is an agonist monoclonal antibody that targets OX40, a costimulatory receptor that is expressed by T cells, and results in activation rather than blockade of the OX40 signaling pathway. MOXR0916 is thought to promote anti-tumour immunity by binding to OX40 on both antigen-experienced effector T cells, thereby enhancing their proliferation and survival, and on activated regulatory T cells, thereby inhibiting their suppressive function. Because Tecentriq and MOXR0916 act through distinct but complementary mechanisms, in combination these investigational immunotherapies have the potential to enhance activation of CD8+ T-cells that mediate anti-tumour immune responses.

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 seven 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.