A new investigational compound, MetMAb, was found to double the survival period for patients with high MET expressing non-small cell lung cancer, without the disease worsening, when taken along with Tarceva, compared to Tarceva plus a placebo, Swiss pharmaceutical company announced at the 35th European Society for Medical Oncology (ESMO) Congress.

Richard Scheller, Ph.D., Head of Genentech Research and Early Development, (gRED), said:

We are pleased to be able to share this new data in lung cancer regarding Tarceva and MetMAb here at ESMO. 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 is a unique monovalent antibody.

Roche presented details on MetMAb’s Phase II randomized, multicenter, double-blind, placebo-controlled trial which compared the safety and efficacy of MetMAb plus Tarceva against a Tarceva plus a placebo in patients with advanced non-small cell lung cancer (NSCLC) who had received prior treatment. They were stratified by the MET receptor expression in their tumor sample via IHC (immunohistochemistry), which was jointly developed with Ventana. They were categorized as MET-low or MET-high.

As of June 8, 2010 (data cut date), adding MetMAb to Tarceva in patients whose tumors were categorized as MET-high (at least 50% of tumor cells staining at IHC chemistry of 2+ or 3+) resulted in an overall survival improvement when compared to Tarceva plus placebo.

No unexpected safety signals were observed among patients receiving MetMAb – it was generally well tolerated. Roche informs that a complete analysis of this trial will be presented shortly at a medical meeting.

A phase III OPTIMAL study demonstrated that first-line Tarceva extended the survival time for patients with advanced non small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) activating mutations, a distinct form of lung cancer, by over one year; nearly three times longer than similar patients would expect with traditional chemotherapy – 13.1 months versus 4.6 months. Also, 56% of the patients receiving Tarceva were progression free, versus 1.7% in the traditional chemotherapy group. 83% of the Tarceva patients experienced tumor shrinkage compared to 36% in the traditional chemotherapy group.

OPTIMAL, a randomized Phase III study, involved 165 patients. Tarceva was compared to gemcitabine/carboplatin chemotherapy in patients with advanced NSCLC with epidermal growth factor receptor (EGFR) activating mutations who had not received prior chemotherapy. Its primary endpoint was progression free survival. Its secondary endpoint included overall survival, overall response rate, quality of life, and safety.

In a communiqué, Roche writes:

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.

It is estimated that approximately 30% of Asian patients and 10% of Caucasian patients have this distinct form of NSCLC, according to Roche.

Roche wrote about Tarceva that:

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.

Roche wrote about MetMAb that:

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 NSCLC. 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.

Source: Roche

Written by Christian Nordqvist