Investor Update

Basel, 09 October 2010

MetMAb, a new compound under investigation, extends the time people with lung cancer live without their disease getting worse

Important new data in lung cancer presented at ESMO, including further evidence of strong efficacy of Tarceva in lung cancer with genetic mutations

  • MetMAb plus Tarceva in lung cancer patients: preliminary data showed a pre-specified group of patients lived nearly twice as long without their disease getting worse than those who received placebo plus Tarceva.1
  • Tarceva in people with a distinct form of lung cancer: helped patients live almost three times longer without their disease getting worse compared to patients who received traditional chemotherapy.2

Roche (SIX: RO, ROG; OTCQX: RHHBY) today announced new data released at the 35th European Society for Medical Oncology (ESMO) congress showing significant progress for people living with lung cancer.

“We are pleased to be able to share this new data in lung cancer regarding Tarceva and MetMAb here at ESMO,” said Richard Scheller, Ph.D., Head of Genentech Research and Early Development, (gRED). “Lung cancer remains an area of high unmet medical need, and our new data with MetMAb is an example of how a targeted, personalized approach may help improve outcomes in this hard to treat disease.”

MetMAb combined with Tarceva in NSCLC

Preliminary results from a phase II study show that a combination of MetMAb, a unique monovalent antibody, with Tarceva (erlotinib) nearly doubled the time people with high MET expressing non-small cell lung cancer (NSCLC) lived without their disease getting worse (progression-free survival or PFS) compared to placebo plus Tarceva (HR=0.560, p=0.0547). The median PFS was improved from 6.4 weeks to 12.4 weeks.

The phase II, randomised, multicentre, double-blind, placebo-controlled study, presented at the European Society for Medical Oncology (ESMO) 2010, evaluated the activity and safety of MetMAb plus Tarceva, versus placebo plus Tarceva in patients who had received prior treatment for advanced NSCLC. Patients were stratified by the MET receptor expression in their tumour sample using immunohistochemistry (IHC), developed in collaboration with Ventana, a member of the Roche Group, and were categorised as MET-high or MET-low, according to a pre-defined scoring system.

The study also showed that as of the data cut date of June 8, 2010, the addition of MetMAb to Tarceva in patients whose tumours expressed high MET levels as assessed by IHC (50% or more of tumour cells staining at IHC intensity of 2+ or 3+) led to an improvement in overall survival (OS) compared to placebo plus Tarceva (HR=0.549 p=0.1113). The median OS was improved from 7.4 months to 7.7 months.

MetMAb treatment was generally well tolerated and no unexpected safety signals were observed. The MET-high population represented 54% of the patients enrolled in the study. The full analysis of the phase II study will be presented at a medical meeting in the near future.

Tarceva first-line nearly triples PFS in NSCLC with EGFR activating mutations

Results from the phase III OPTIMAL study show that first-line Tarceva (erlotinib) extended the time people with a distinct form of lung cancer lived without their disease getting worse (progression free survival – PFS) to more than one year, which was almost three times longer than for patients who received traditional chemotherapy (median 13.1 vs. 4.6 months, HR=0.16, p<0.0001).

After one year over half (56%) of all Tarceva treated patients with advanced non small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) activating mutations were progression free compared to 1.7% of people who received chemotherapy. In addition, more than twice as many patients who received Tarceva experienced shrinkage of their tumours compared to those who received chemotherapy (83% vs. 36%; p < 0.00001).

Data from the OPTIMAL study will be shared with the European Medicines Agency to support the label extension currently under review for use of Tarceva as a first-line monotherapy treatment for people with advanced NSCLC with EGFR activating mutations.

Tarceva is the only EGFR inhibitor approved for use in maintenance and second-line treatment settings in patients with advanced or metastatic NSCLC irrespective of the presence of EGFR activating mutations.

A licence for Tarceva for use in the first-line setting would allow physicians to personalise early treatment according to EGFR activating mutation status, while people with NSCLC without EGFR activating mutations would continue to benefit from treatment with Tarceva in later lines of therapy.

As many as one in three (30%) Asian patients with lung cancer and an estimated one in ten (10%) lung cancer patients in the Western population have this distinct form of NSCLC.3,4

About the OPTIMAL study

  • OPTIMAL (CTONG 0802) is a randomised, phase III study evaluating the efficacy of first-line Tarceva versus gemcitabine/carboplatin chemotherapy in patients with advanced NSCLC with epidermal growth factor receptor (EGFR) activating mutations who have not received prior chemotherapy. The study involving 165 patients was initiated by Tongji University, Shanghai, China with support from Roche Shanghai.
  • The primary endpoint of the study was progression free survival (PFS). Secondary endpoints include overall survival, overall response rate, quality of life and safety.
  • Overall PFS was significantly prolonged with Tarceva vs. chemotherapy. People who received Tarceva lived a median of 13.1 months without their disease getting worse, whereas those who received chemotherapy lived a median of 4.6 months [HR=0.16 (0.10-0.26), p<0.0001].
  • After one year 56% of all patients receiving Tarceva were alive and progression free compared with only 1.7% of people in the chemotherapy group.
  • The objective response rate was significantly improved for people receiving Tarceva compared to those receiving chemotherapy (83% vs. 36%, p < 0.00001).
  • Overall survival data are not yet mature.
  • Safety data confirm the favourable safety profile of Tarceva with a lower incidence of adverse events and serious adverse events observed in patients receiving Tarceva compared with those receiving chemotherapy. No unexpected safety signals were reported in either group.

OPTIMAL data presentation at the 35th European Society for Medical Oncology (ESMO) congress: Chest Tumours I Session, Silver Hall, Saturday 9 October11:00 CET: Efficacy results from the randomized phase III OPTIMAL (CTONG 0802) study comparing first-line erlotinib versus carboplatin (CBDCA) plus gemcitabine (GEM), in Chinese advanced non-small-cell lung cancer (NSCLC) patients (pts) with EGFR activating mutations, C. Zhou et al.

About Tarceva

Tarceva is a once-daily, oral non-chemotherapy treatment for the treatment of advanced or metastatic NSCLC. It has been shown to potently inhibit (epidermal growth factor) EGFR, a protein involved in the growth and development of cancers. Tarceva is the first and only EGFR inhibitor to be approved for use in maintenance and second-line treatment settings in patients with advanced or metastatic NSCLC. It is also the only EGFR inhibitor to have shown activity in patients irrespective of EGFR activating mutation status. In both maintenance and second-line settings, Tarceva has a proven and significant survival and symptom benefit without the side effects associated with chemotherapy. In addition, Tarceva in combination with chemotherapy is the first treatment in over ten years to be approved for patients with advanced pancreatic cancer. Since initial launch Tarceva has been used to treat more than 400,000 patients worldwide and is now approved in more than 100 countries.

About the MetMAb study

  • OAM4558g is a global randomised, double-blind phase II study comparing MetMAb (15mg/kg IV q3wks) plus erlotinib (ME) to placebo plus erlotinib (PE) in 2nd/3rd line NSCLC. 128 patients were randomised from 3/2009 to 3/2010 to ME (n=64) or PE (n=64).
  • Eligible patients on the PE arm were allowed to crossover to ME following progression. Patients were stratified by histology, ECOG PS and smoking status. Archival tissue was mandatory for determination of MET expression by IHC.
  • Co-primary endpoints of the study were progression free survival (PFS) in the MET-high and overall populations. Secondary endpoints include overall survival and safety.
  • As of June 8, 2010 data cut, PFS was significantly prolonged with MetMAb plus erlotinib in MET-high NSCLC patients who lived a median of 12.4 weeks without their disease getting worse. PFS in MET-high NSCLC patients who received placebo plus erlotinib lived a median of 6.4 weeks without their disease getting worse (HR=0.560 p=0.0547).
  • Conversely, MET-low NSCLC patients had worse PFS when treated with MetMAb plus erlotinib as compared to placebo plus erlotinib (HR=2.012, p=0.0354).
  • Overall survival (OS) was prolonged in MET-high NSCLC patients on MetMAb plus erlotinib compared to MET-high patients on placebo plus erlotinib (median OS of 7.7 months with MetMAb vs. 7.4 months on control arm, HR=0.549, p=0.1113).
  • MET-low NSCLC patients had worse OS when treated with MetMAb plus erlotinib as compared to placebo plus erlotinib (HR=3.256, p=0.0142).
  • No unexpected safety signals were observed.

MetMAb data presentation at the 35th European Society for Medical Oncology (ESMO) congress: Chest Tumours I Session, Silver Hall, Saturday 9 October 12:00 CET: Randomised multicenter double-blind placebo-controlled phase II study evaluating MetMAb, an antibody to met receptor, in combination with erlotinib, in patients with advanced non-small-cell lung cancer, D. Spigel et al.

About MetMAb

MetMAb is a unique monoclonal monovalent antibody (one-armed antibody) that binds specifically to the cell surface MET receptor, blocking HGF-mediated activation. MET can be inappropriately activated in many cancers such as lung, metastatic breast, kidney and gastric by different mechanisms, such as over expression and a variety of mutations, which lead to invasive cancer growth. Abnormal MET activation has been associated with worse prognosis in a variety of tumour types, including NSCLC5, and has been implicated in resistance to EGFR inhibition in EGFR-mutated NSCLC6.  The predominant mechanism by which MET becomes activated is through binding of its ligand, hepatocyte growth factor (HGF). MetMAb binds specifically to MET, blocking HGF-mediated activation. Dual inhibition of Met/EGFR may result in promising activity in NSCLC.

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, virology, inflammation, metabolism and CNS. Roche is also the world leader in in-vitro diagnostics, tissue-based cancer diagnostics and a pioneer in diabetes management. Roche’s personalised healthcare strategy aims at providing medicines and diagnostic tools that enable tangible improvements in the health, quality of life and survival of patients. In 2009, Roche had over 80’000 employees worldwide and invested almost 10 billion Swiss francs in R&D. The Group posted sales of 49.1 billion Swiss francs. Genentech, United States, is a wholly owned member of the Roche Group. Roche has a majority stake in Chugai Pharmaceutical, Japan. For more information:

All trademarks used or mentioned in this release are protected by law.

1) D. Spigel et al.MetMAb in combination with Tarceva, ESMO 2010, Abstract LBA15
2) C. Zhou et al. Tarceva OPTIMAL, ESMO 2010, Abstract LBA13
3) Rosell R, Moran T, Queralt C, et al. Screening for epidermal growth factor receptor mutations in lung cancer. N Engl J Med 2009;361:958–67
4) Mitsudomi T, Kosaka T, Yatabe Y. Biological and clinical implications of EGFR mutations in lung cancer. Int J Clin Oncol 2006;11:190–8
5) Lai AZ, Abella JV, Park M. Crosstalk in Met receptor oncogenesis. Trends Cell Biol. 2009;19:542
6) Engleman JA, et al. Mechanisms of Acquired Resistance to Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors in Non–Small Cell Lung Cancer. Clinical Cancer Research 14; 2895, May 2008