Roche announced final results from a randomised, multicentre, double-blind phase II study with its investigational personalised medicine, MetMAb, in people with previously-treated advanced non-small cell lung cancer (NSCLC). MetMAb is a unique one-armed investigational antibody designed to target Met, a protein (or receptor) associated with a poor outcome in many cancers. The study showed that people whose tumours had high levels of Met, as determined by a companion diagnostic, lived twice as long without their disease getting worse (progression-free survival, [PFS]) when they received MetMAb plus Tarceva (erlotinib) compared to Tarceva alone.

Overall survival (OS) was evaluated as an exploratory endpoint and the study showed MetMAb plus Tarceva tripled the time people with this form of advanced NSCLC lived compared with Tarceva alone. There were no unexpected safety signals from the combination of MetMAb with Tarceva and the safety profile of Tarceva was consistent with previous studies of the medicine in people with solid tumours.

“The unique design of MetMAb and the development of a companion diagnostic test allowed us to target a specific pathway that may be driving cancer growth,” said Hal Barron M.D., chief medical officer and head, global product development. “These results support further investigation of MetMAb as a potential personalised medicine for people with lung cancer and we plan to start a phase III study later this year.”

In the phase II MetMAb study, people with previously-treated NSCLC had their tumours analysed for Met protein levels using an immunohistochemistry (IHC) test developed by Roche’s Tissue Diagnostics Company, Ventana Medical Systems. Tumours with high Met protein levels were classified as Met diagnostic-positive, and with low Met protein levels as Met diagnostic-negative.

In the overall population of patients with high and low Met expression, the combination of MetMAb and Tarceva did not show a statistically significant improvement in PFS compared to Tarceva alone (HR=1.09, p=0.687, median PFS: 2.2 months vs. 2.6 months).

In people with high Met tumours, those who received MetMAb plus Tarceva had a statistically significant doubling of PFS compared to those who received Tarceva alone (HR=0.53, p=0.04). The median PFS was improved from 1.5 months to 2.9 months.

The addition of MetMAb to Tarceva also led to a statistically significant improvement in OS compared to Tarceva alone (HR 0.37, p=0.002) in people with high Met tumours. The improvement in median OS was tripled from 3.8 months to 12.6 months.

The most common adverse events (AEs) of any grade (= 15% in any subgroup or study arm, regardless of Met diagnostic status) included rash, diarrhoea, fatigue, decreased appetite, nausea, shortness of breath, cough, acne-like rash, infections, dry skin, anaemia (low red blood cell count), vomiting, fever, pain, chest pain, back pain and peripheral oedema (swelling of the hands and feet).

Of these AEs, only peripheral oedema was seen at a higher rate (more than 10%) in the combination group compared with the Tarceva only group (23.2% vs. 7.5%).

Although PFS and OS were improved in people classified as having high Met tumours, those with low Met tumours had worse outcomes when given MetMAb plus Tarceva as compared to Tarceva alone (PFS: HR=1.82, p=0.050, median PFS 1.4 months vs. 2.7 months; OS: HR=1.78, p=0.158, median OS=8.1 months vs. 15.3 months). This result highlights the importance of a companion diagnostic in evaluating the efficacy of experimental therapeutics to distinguish between the people who may potentially benefit from a new medicine as well as those who may not.

Full results of the OAM4558g study will be presented during an oral abstract session at the 47th Annual Meeting of the American Society of Clinical Oncology (ASCO) on June 5, 2011, by David R. Spigel, M.D., the principal investigator and programme director of Lung Cancer Research at the Sarah Cannon Research Institute in Nashville, Tennessee (Abstract 7505, Sunday, June 5, 10:00 - 10:15 AM CT, Hall D1).

OAM4558g is a global randomised, double-blind Phase II study comparing MetMAb plus Tarceva to placebo plus Tarceva in people with previously treated advanced NSCLC. One hundred and thirty-seven patients were randomised equally between the two arms between March 2009 and August 2010. Eligible patients in the placebo plus Tarceva arm were allowed to receive MetMAb following progression.

Patients’ tumours were classified as Met diagnostic-positive (high Met) or Met diagnostic-negative (low Met) depending on the results of the investigational companion diagnostic test.

The primary endpoint of the study was PFS in the high Met and overall populations. Additional endpoints included OS and the safety profile.

Many cancers are the result of abnormal growth, replication and survival of cells. These factors are controlled by signalling pathways that relay information from the outside to the inside of cells, via receptors. Met is a receptor, expressed on the surface of epithelial and endothelial cells, which is activated by a protein, called hepatocyte growth factor (HGF). Signalling through the HGF/Met pathway can become abnormal and cause healthy cells to become cancerous. By preventing the binding of HGF to Met, the ability of cancerous cells to grow, replicate, survive and spread is inhibited.1,2,3

MetMAb is a unique, monovalent (one-armed), monoclonal antibody designed to block Met signalling in cancer cells by binding specifically to the cell surface Met receptor, blocking HGF-mediated activation. MetMAb, an investigational medicine, is currently only available through clinical trials.

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 receptor (EGFR), a protein involved in the growth and development of cancers. Tarceva is a registered trademark of OSI Pharmaceuticals, LLC, a member of the Astellas global group of companies.

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.