ORLANDO, Fla., (May 17, 2005) – Amgen Inc. (Nasdaq: AMGN), the world's largest biotechnology company, and Abgenix, Inc. (Nasdaq: ABGX), a leading antibody development company, today announced updated results from an ongoing Phase 2 study of panitumumab, a fully human monoclonal antibody directed against the epidermal growth factor receptor (EGFr). The results demonstrate that panitumumab has antitumor activity when administered as a single-agent treatment to patients with metastatic colorectal cancer (mCRC) who have failed standard chemotherapy. An independent central radiology review determined that treatment with panitumumab resulted in a nine percent overall response rate and median time to progression of 11.4 weeks. [Abstract #3520]
The data were presented today at the 41st Annual Meeting of the American Society of Clinical Oncology (ASCO). Investigators reported that patients with mCRC tumors expressing the EGFr protein who received panitumumab monotherapy demonstrated a median survival time of 37.6 weeks and a median duration of tumor response of 18.1 weeks. Stabilization of disease was observed in 29 percent of patients (n=43). Median progression-free survival time was 13.6 weeks.
"These data confirm previously reported safety and response findings in patients with metastatic colorectal cancer who have previously failed multiple lines of chemotherapy," said Imtiaz A. Malik, MD, professor of medicine, Loma Linda University Cancer Institute, Loma Linda, Calif. and one of the study's lead investigators. "Panitumumab's efficacy and safety data from Phase 1 and Phase 2 clinical trials to date suggest that panitumumab may provide an additional avenue for oncologists to manage the disease."
Patients in the study (n=148) were previously treated with 5FU (with or without leucovorin) and either irinotecan or oxaliplatin, or both. Patients received 2.5 mg/kg of panitumumab by weekly one-hour intravenous infusion without premedication. Tumor responses were confirmed no less than four weeks after the initial response was observed.
In this Phase 2 study, the most common side effect was skin toxicity (95 percent, 7 percent grade 3). Other side effects experienced by some patients were fatigue, nausea and mild diarrhea. One infusion reaction (grade 3) was reported per investigator assessment and the patient continued on full-dose panitumumab with pre-medication. There were no instances of anaphylaxis observed. In those patients tested who had a baseline and a post-baseline assessment (n=107), no human antihuman antibodies (HAHAs) formation was observed.
Phase 1 Open-Label Dose Escalation Trial Suggests Panitumumab May Provide for Flexible Dosing Schedules in Cancer Patients [Poster K4, Abstract #3059]
Additional data from a Phase 1 open-label dose escalation trial were presented by Louis M. Weiner, MD, chairman, department of medical oncology, and vice president, translational research at Fox Chase Cancer Center, Philadelphia, Pa. Exposure and tolerability profiles were similar between weekly, every-other-week and every-three-week dosing schedules.
"We are very encouraged by the safety profile at various doses of this antibody in cancer patients and in different types of cancers. We look forward to the continued evaluation of panitumumab, a promising antibody cancer therapeutic," said Dr. Weiner.
Patients (n=96) were randomized to receive four infusions of panitumumab at different dose levels and schedules ranging from 0.01 to 5.0 mg/kg once per week, 6.0 mg/kg once every two weeks or 9.0 mg/kg once every three weeks administered by intravenous infusion with no premedication required.
For further information concerning ongoing clinical trials involving panitumumab please visit, http://www.amgentrials.com/.
About Colorectal Cancer
Colorectal cancer is the third most common cancer diagnosed in men and in women in the United States. The American Cancer Society estimates that about 104,950 new cases of colon cancer (48,290 men and 56,660 women) and 40,340 new cases of rectal cancer (25,530 men and 16,810 women) will be diagnosed in 2005.
Co-developed by Amgen and Abgenix, panitumumab is an investigational product in a novel class of targeted cancer treatments called epidermal growth factor receptor (EGFr) inhibitors. Panitumumab (formerly ABX-EGF) is the first fully human monoclonal antibody directed against EGFr and is being evaluated as both a monotherapy and in combination with other agents for the treatment of various types of cancer, including colorectal, lung and kidney. Panitumumab was generated with Abgenix's XenoMouse® technology, which creates a fully human monoclonal antibody that contains no murine (mouse) protein. The fully human nature of panitumumab may result in a safety profile with a low incidence of infusion reactions and antigenicity. These are attributes currently being investigated in clinical trials. Pivotal clinical studies evaluating panitumumab as a monotherapy in colorectal cancer patients who have failed standard chemotherapy are ongoing with an every-other-week dosing regimen.
About the Epidermal Growth Factor Receptor (EGFr)
Although EGFr normally helps regulate the growth of many different cells in the body, EGFr can also stimulate cancer cells to grow. In fact, many cancer cells actually require signals mediated by EGFr for their survival. Residing on the surface of these tumor cells, EGFr is activated when naturally occurring proteins in the body, epidermal growth factor (EGF) or transforming growth factor alpha (TGFá), bind to it. This binding changes the shape of EGFr, which, in turn, triggers internal cellular signals that stimulate tumor cell growth.
Panitumumab binds to EGFr, preventing EGF and TGFá from binding to the receptor and interfering with the signals that would otherwise stimulate growth of the cancer cell and allow it to survive.
Source: Eurekalert & othersLast reviewed: By John M. Grohol, Psy.D. on 21 Feb 2009
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