Boehringer Ingelheim Pharmaceuticals, Inc. Release: Interim Data Announced for BIBF 1120 as Compared to Bevacizumab in Combination Chemotherapy in Metastatic Colorectal Cancer

STOCKHOLM, Sept. 27, 2011 /PRNewswire/ -- Boehringer Ingelheim Pharmaceuticals, Inc. today announced interim results from an exploratory clinical trial evaluating its investigational compound BIBF 1120 in patients with metastatic colorectal cancer (mCRC). In this Phase I/II study of 126 patients comparing BIBF 1120 as first-line treatment to bevacizumab, both in combination with mFOLFOX6 (6th modified regimen of folinic acid [leucovorin], fluorouracil, and oxaliplatin), the progression-free survival (PFS) rate at 9 months was 63 percent (95% CI: 50%-75%) in the BIBF 1120 arm and 69% (95% CI: 53%-86%) in the bevacizumab arm.(1) The median PFS was numerically similar between both groups at 10.6 months ([95% CI: 9.4-12.3] for the BIBF 1120 arm and [95% CI: 9.1-NA] for the bevacizumab arm).(2)

The study, presented at the Presidential Session of the 2011 European Multidisciplinary Cancer Congress in Stockholm, Sweden, also showed that the objective response rate (ORR), a measure of tumor shrinkage, was 61 percent in the BIBF 1120 arm and 54 percent in the bevacizumab arm.(1)

While both treatment arms showed similar safety profiles, a lower incidence of serious adverse events was seen in patients taking BIBF 1120 compared to those taking bevacizumab (34% vs. 54%).(2) Adverse events (grade 3 or higher) experienced by at least 10 percent of patients in the BIBF 1120 and bevacizumab arms included neutropenia (32% vs. 24%), diarrhea (15% vs. 12%), neurotoxicity (14% vs. 10%), paresthesia (13% vs. 12%) and asthenia (11% vs. 10%).(1) Patients receiving BIBF 1120 experienced a lower frequency of serious gastrointestinal adverse events than those receiving bevacizumab (12% vs. 29%).(2)

The study is ongoing in order to collect overall survival (OS) data. Phase III trials with larger patient populations will be considered to confirm these results and to further investigate the potential of BIBF 1120 in mCRC.

"The study results allow us to move forward and to investigate BIBF 1120 in patients with advanced colorectal carcinoma enabling us to further explore this potential additional treatment option," said Christopher Corsico, M.D., M.P.H., Sr. Vice President, Medicine and Regulatory, Boehringer Ingelheim Pharmaceuticals, Inc. "BIBF 1120 is another example of Boehringer Ingelheim's continued commitment to advancing oncology research by investigating our compounds in a variety of tumor types."

BIBF 1120 is an investigational orally-administered triple angiokinase inhibitor that targets three of the receptor tyrosine kinases shown to aid in the regulation of angiogenesis, or the formation of blood vessels: fibroblast growth factor receptor (FGFR), platelet-derived growth factor receptor (PDGFR) and vascular endothelial growth factor receptor (VEGFR).(3)

About Trial Nr. NCT 00904839

Abstract Details

• Abstract title: A Phase I/II, Open-label, Randomised Study of BIBF 1120 Plus mFOLFOX6 Compared to Bevacizumab Plus mFOLFOX6 in Patients with Metastatic Colorectal Cancer
• Abstract number: 14LBA
• Speaker: Van Cutsem, E. (B)
• Session being presented: Presidential Session IV: Best and Late Breaking Abstracts
• Location: Hall A1
• Date: September 27, 2011, 3:00 5:00 a.m. EDT

The primary objective of this Phase I/II study is to evaluate PFS rate at 9 months of patients receiving BIBF 1120 in combination with mFOLFOX6 compared to patients receiving bevacizumab combined with mFOLFOX6 in first line metastatic colorectal cancer.(4) The 9-month PFS rate was defined as the percentage of patients whose disease did not progress or who did not die 9 months after the treatment had started.(4)

About Colorectal Cancer

Although mortality rates for colorectal cancer in the U.S. have declined over the past two decades, an estimated 49,380 related deaths are expected to occur in 2011, which will account for about 9 percent of all cancer deaths.(5)

About Boehringer Ingelheim in Oncology

Building on scientific expertise and excellence in the fields of pulmonary and cardiovascular medicine, metabolic disease, neurology, virology and immunology, Boehringer Ingelheim has embarked on a major research program to develop innovative cancer drugs. Working in close collaboration with the international scientific community and a number of the world's leading cancer centers, Boehringer Ingelheim is committed to discovering and developing novel cancer treatments. This commitment is underpinned by using advances in science to develop a range of targeted therapies in areas of medical need, including seven investigational compounds in different phases of development for solid tumors and hematological cancers.

The current focus of research includes compounds in three areas: angiogenesis inhibition, signal transduction inhibition and cell-cycle kinase inhibition. Afatinib is currently in phase III clinical development in NSCLC and breast cancer. Apart from afatinib, Boehringer Ingelheim's late-stage oncology portfolio includes BIBF 1120, an investigational orally-administered triple angiokinase inhibitor that targets three of the receptor tyrosine kinases shown to aid in the regulation of angiogenesis (formation of blood vessels): fibroblast growth factor receptor (FGFR), platelet-derived growth factor receptor (PDGFR) and vascular endothelial growth factor receptor (VEGFR). As angiogenesis plays a pivotal role in the growth of all solid tumors, (6,7) BIBF 1120 is currently being investigated in a number of cancers including NSCLC, ovarian, hepatocellular and colorectal cancers. BIBF 1120 and afatinib are not approved by the FDA; their safety and efficacy have not been established.

In the area of cell-cycle kinase inhibition, Boehringer Ingelheim is developing inhibitors of polo-like kinase (Plk), a protein that is involved in the processes of cell division. These molecules are in the earlier stages of clinical development.

About Boehringer Ingelheim Pharmaceuticals, Inc.

Boehringer Ingelheim Pharmaceuticals, Inc., based in Ridgefield, CT, is the largest U.S. subsidiary of Boehringer Ingelheim Corporation (Ridgefield, CT) and a member of the Boehringer Ingelheim group of companies.

The Boehringer Ingelheim group is one of the world's 20 leading pharmaceutical companies. Headquartered in Ingelheim, Germany, it operates globally with 145 affiliates and more than 42,000 employees. Since it was founded in 1885, the family-owned company has been committed to researching, developing, manufacturing and marketing novel products of high therapeutic value for human and veterinary medicine.

As a central element of its culture, Boehringer Ingelheim pledges to act socially responsible. Involvement in social projects, caring for employees and their families, and providing equal opportunities for all employees form the foundation of the global operations. Mutual cooperation and respect, as well as environmental protection and sustainability are intrinsic factors in all of Boehringer Ingelheim's endeavors.

For more information, please visit http://us.boehringer-ingelheim.com and follow us on Twitter at http://twitter.com/boehringerus.

References

1. Van Cutsem et al. A Phase I/II, open-label, randomised study of BIBF 1120 plus mFOLFOX6 compared to bevacizumab plus mFOLFOX6 in patients with metastatic colorectal cancer. Late-breaking abstract 1199.51, European Cancer Organization Congress, Stockholm, September 2011.

2. Van Cutsem et al. A Phase I/II, Open-label, Randomised Study of BIBF 1120 Plus mFOLFOX6 Compared To Bevacizumab Plus mFOLFOX6 In Patients With Metastatic Colorectal Cancer. Oral presentation, European Cancer Organization Congress, Stockholm, September 2011.

3. Hilberg F et al. BIBF1120: Triple angiokinase inhibitor with sustained receptor blockade and good anti-tumor efficacy. Cancer Research 2008;68(12): 4774-4782.

4. Van Cutsem et al. A Phase I/II, open-label, randomised study of BIBF 1120 plus mFOLFOX6 compared to bevacizumab plus mFOLFOX6 in patients with metastatic colorectal cancer. Clinical Trial Protocol (1199.51), Revised 23 June 2009.

5. American Cancer Society. Cancer Facts and Figures: 2011. Available at: http://www.cancer.org/acs/groups/content/@epidemiologysurveilance/documents/document/acspc-029771.pdf. Last accessed September 15, 2011.

6. Folkman N. Clinical Applications of Research on Angiogenesis. New England Journal of Medicine 1995;333: 1757-1763.

7. Ellis, L.M. and Hicklin, D.J. VEGF-targeted therapy: mechanisms of anti-tumour activity. Nature Reviews Cancer 2008;8: 579-591.

SOURCE Boehringer Ingelheim Pharmaceuticals, Inc.