Wednesday, May 18, 2011

MetMAb in Combination with Tarceva Doubled the Time People with Lung Cancer Lived without Their Disease Getting Worse

Genentech's Investigational Personalized Medicine Showed Promising Final Phase II Results in People With a Form of Lung Cancer

South San Francisco, Calif. -- May 18, 2011 --

Genentech, a member of the Roche Group (SIX: RO, ROG; OTCQX: RHHBY), today announced final results from a randomized, multicenter, double-blind Phase II study with its investigational personalized 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 tumors had high levels of Met, as determined by a companion diagnostic, lived twice as long without their disease getting worse (progression-free survival or 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 tumors.


"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 personalized 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 tumors analyzed for Met protein levels using an immunohistochemistry (IHC) test developed by Roche's Tissue Diagnostics Company, Ventana Medical Systems. Tumors 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 (hazard ratio [HR]=1.09, p=0.687, median PFS: 2.2 months for the combination vs. 2.6 months for Tarceva alone).
  • In people with high Met tumors, 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 tumors. 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 percent in any subgroup or study arm, regardless of Met diagnostic status) included rash, diarrhea, fatigue, decreased appetite, nausea, shortness of breath, cough, acne-like rash, infections, dry skin, anemia (low red blood cell count), vomiting, fever, pain, chest pain, back pain and peripheral edema (swelling of the hands and feet).
  • Of these AEs, only peripheral edema was seen at a higher rate (more than 10 percent) in the combination group compared with the Tarceva only group (23.2 percent vs. 7.5 percent).

Although PFS and OS were improved in people classified as having high Met tumors, those with low Met tumors 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 for the combination vs. 2.7 months for Tarceva alone; OS: HR=1.78, p=0.158, median OS: 8.1 months for the combination vs. 15.3 months for Tarceva alone). 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 program director of Lung Cancer Research at the Sarah Cannon Research Institute in Nashville, Tenn. (Abstract #7505, Sunday, June 5, 10:00 - 10:15 a.m. CDT, Hall D1).


About the MetMAb Phase II Study Design
OAM4558g is a global, randomized, 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 randomized 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' tumors 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.


About the Met Pathway
Many cancers are the result of abnormal growth, replication and survival of cells. These factors are controlled by signaling 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). Signaling 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.


About MetMAb
MetMAb is a unique, monovalent (one-armed), monoclonal antibody designed to block Met signaling 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.


About Tarceva
Tarceva is approved for patients with advanced NSCLC whose cancer has not spread or grown after initial treatment with certain types of chemotherapy (maintenance treatment). Tarceva is also approved for patients with advanced NSCLC whose cancer has spread or grown after receiving at least one chemotherapy regimen (second-/third-line treatment). Tarceva is not meant to be used at the same time as certain types of chemotherapy for NSCLC.


Important Safety Information for Tarceva in Advanced NSCLC
There have been reports of serious Interstitial Lung Disease (ILD)-like events including deaths in patients taking Tarceva. Serious side effects (including deaths) in patients taking Tarceva include liver and/or kidney problems; gastrointestinal (GI) perforations (the development of a hole in the stomach, small intestine, or large intestine); and severe blistering skin reactions including cases similar to Stevens-Johnson syndrome.


Eye irritation and damage to the cornea have been reported in patients taking Tarceva. Difficulty with blood clotting, and bleeding events, including gastrointestinal and non-gastrointestinal bleeding have been reported in clinical studies. Women should avoid becoming pregnant and avoid breastfeeding while taking Tarceva. Patients should call their doctor right away if they have these signs or symptoms: new or worsening skin rash; serious or ongoing diarrhea, nausea, loss of appetite, vomiting, or stomach pain; new or worsening shortness of breath or cough; fever; eye irritation. Rash and diarrhea were the most common side effects associated with Tarceva in the NSCLC clinical studies.


For full prescribing information on Tarceva, please visit http://www.tarceva.com.


Tarceva is a registered trademark of OSI Pharmaceuticals, LLC, a member of the Astellas global group of companies.


About Genentech
Founded more than 30 years ago, Genentech is a leading biotechnology company that discovers, develops, manufactures and commercializes medicines to treat patients with serious or life-threatening medical conditions. The company, a member of the Roche Group, has headquarters in South San Francisco, California. For additional information about the company, please visit http://www.gene.com.


# # #