Investor Update

Basel, 11 December 2015

Roche presents early data on investigational cancer immunotherapy atezolizumab in combination with nab-paclitaxel chemotherapy in patients with specific type of advanced breast cancer

  • The combination of atezolizumab plus nab-paclitaxel showed that approximately two thirds of people responded to treatment regardless of their PD-L1 (programmed death-ligand 1) status
  • Data showed atezolizumab can be combined with nab-paclitaxel to enhance the immune system to recognise and destroy cancer cells

Roche (SIX: RO, ROG; OTCQX: RHHBY) presented results from a phase Ib study of the investigational cancer immunotherapy atezolizumab (MPDL3280A) used in combination with nab-paclitaxel in patients with metastatic triple-negative breast cancer (TNBC). The study showed that the combination shrank tumours (overall response rate, including unconfirmed responses) in 70.8% of people, [n=24; 95% confidence interval, (CI): 48.9, 87.4]. 11 of 17 responses (65%) continued on treatment at time of data cut-off. The highest overall response rate observed [88.9% (CI: 51.7, 99.7)] was in people receiving their initial (1st line) treatment for metastatic disease, with 1 confirmed complete responder. Responses were observed in both PD-L1 positive and PD-L1 negative patients. In addition, some patients with evidence of RECIST based progressive disease developed further response with continued treatment. Adverse events (AEs) were consistent with what has previously been reported for treatment of nab-paclitaxel alone, with 56% of patients (n=32) experiencing Grade 3–4 AEs. These data were presented at the San Antonio Breast Cancer Symposium 2015 congress.1

“We are encouraged that a high proportion of people responded to combined treatment with atezolizumab and nab-paclitaxel chemotherapy, regardless of their PD-L1 expression,” said Sandra Horning, MD, Roche’s Chief Medical Officer and Head of Global Product Development. “This result indicates that combinations may provide a way to increase the benefits of atezolizumab in a wide range of people with triple-negative breast cancer."

Based on these results and the observed activity of single-agent atezolizumab in these patients, Roche is evaluating the combination of atezolizumab and nab-paclitaxel in a phase III study (IMpassion130; NCT02425891) of patients with previously untreated metastatic TNBC.

About the phase Ib study of atezolizumab in combination with nab-paclitaxel

  • This part of the multicentre, multi-arm phase Ib study aimed to evaluate atezolizumab in combination with weekly nab-paclitaxel in patients with metastatic TNBC previously treated with systemic cytotoxic therapy
  • Primary endpoints were safety and tolerability, with secondary endpoints including efficacy using RECIST v1.1 criteria (best overall response, objective response rate, duration of response, progression-free survival), pharmacokinetics, as well as biomarker analyses
  • Patients received atezolizumab 800 mg once every 2 weeks (days 1 and 15) with nab-paclitaxel 125 mg/m2 weekly (days 1, 8 and 15) for 3 weeks in 4-week cycles, until loss of clinical benefit
  • All patients were women with a median age of 58 years (range 32–75 years)
  • PD-L1 expression was assessed for both tumour cells (TCs) and immune cells (ICs); people were scored as IC0, 1, 2 or 3 and TC0, 1, 2 or 3 with an immunohistochemistry (IHC) test being developed by Roche Tissue Diagnostics
  • Expression of PD-L1 in TNBC was mostly restricted to IC

Efficacy

Summary of Best Overall Responses by RECIST v1.1

Objective Response Rate by PD-L1 Expression Levela

Safety

Treatment-related Adverse Eventsa

AEs, adverse events

About triple-negative breast cancer

Triple-negative breast cancer (TNBC) refers to any breast cancer that does not express oestrogen receptor (ER), progesterone receptor (PR) or overexpress the HER2 receptor. Approximately 10%–20% of all breast cancers are TNBC, and have a worse prognosis compared with other breast cancer subtypes.2, 3 TNBC is associated with more frequent recurrence, shorter disease-free interval and earlier visceral metastases. Patients with metastatic TNBC have decreased survival compared with patients with other subtypes of breast cancer, with a median survival of 6 to 13 months.4, 5, 6 Currently, chemotherapy is the mainstay of treatment for metastatic TNBC, although clinical practice patterns vary worldwide.

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 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. 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 chemotherapy.

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.

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References
1.Adams S, et al. Safety and clinical activity of atezolizumab (anti-PD-L1) in combination with nab-paclitaxel in patients with triple-negative breast cancer, Abstract number: 850477. 10th December, 07.30  San Antonio, TX, United States
2.Hudis CA, Gianni L.Oncologist 2011;16(suppl 1):1-11.
3.Aysola K, et al. Hereditary Genet 2013;2013(suppl 2)
4.Zhang J, et al. Oncotarget 2015 Oct 3 [Epub ahead of print]
5.Liedtke C, et al. J Clin Oncol 2008;26(8):1275-1291.
6.Dent R, et al. Breast Cancer Res Treat. 2009; 115:423-428.