Boehringer Ingelheim to present new data at ASCO annual meeting regarding its investigational compound afatinib in EGFR-mutation positive patients with advanced NSCLC

RIDGEFIELD, Conn., May 25 /PRNewswire/ -- Boehringer Ingelheim Pharmaceuticals, Inc. will present new phase Ib data at the 2011 American Society of Clinical Oncology (ASCO) annual meeting in Chicago (June 3-7) that indicates combining its investigational therapy afatinib (BIBW 2992) with cetuximab at the maximum tested dose controlled disease in all (n=22) treated epidermal growth factor receptor (EGFR)-mutation positive patients with non-small cell lung cancer (NSCLC) who developed acquired resistance to treatment with a reversible EGFR tyrosine kinase inhibitor (TKI). Researchers observed a tumor size reduction of up to 76 percent over a treatment period of up to five months.(1) The most common drug-related adverse events were rash and diarrhea, with three patients (11.5%) experiencing Grade 3 rash. Afatinib is an orally-administered irreversible inhibitor of the erbB family of receptor tyrosine kinases, specifically EGFR and HER2.  It is in late-stage development in advanced NSCLC and breast cancer.

Boehringer Ingelheim and QIAGEN are pleased that ASCO and the National Comprehensive Cancer Network (NCCN), two leading oncology organizations, recently recommended EGFR mutation testing for patients with metastatic or recurrent NSCLC.  These recommendations underscore the importance of genetic tumor testing to predict patient response to certain treatments, enabling personalized healthcare.  Boehringer Ingelheim has partnered with QIAGEN to develop a real-time polymerase chain reaction assay (real-time PCR) companion diagnostic test for afatinib that, if approved, could help physicians identify which patients may benefit from EGFR-targeted therapies.

"The ASCO and NCCN EGFR mutation testing recommendations reinforce the importance of identifying the appropriate NSCLC patients for clinical trials," said Christopher Corsico, M.D., M.P.H., Senior Vice President, Medicine and Regulatory, Boehringer Ingelheim Pharmaceuticals, Inc. "Boehringer Ingelheim is committed to studying afatinib in patients with advanced NSCLC with EGFR mutations, in addition to other patient populations."

About the Afatinib Data to be Presented at 2011 ASCO Annual Meeting

This phase Ib study involved 26 EGFR-mutation positive patients with NSCLC who acquired resistance to a reversible EGFR TKI (erlotinib or gefitinib), potentially due to the emergence of a second mutation called T790M.  The T790M mutation is found in roughly 50 percent of the tumors from patients who develop acquired resistance to reversible EGFR TKIs.(2)  Patients in the study received afatinib 40 mg daily with escalating dose cohorts of bi-weekly cetuximab at 250 and 500 mg/m2.  Tumor tissue was collected at or after the emergence of acquired resistance for genetic testing.(1)

Twenty-two of the 26 patients in the study received the pre-defined maximum dose of afatinib 40 mg daily plus cetuximab 500 mg/m2.  The most common drug-related adverse events were Grade 1/2 rash (35% and 46%, respectively) and Grade 1/2 diarrhea (50% and 19%, respectively).  Three patients (11.5%) experienced Grade 3 rash.  In addition to the disease control rates observed, confirmed partial responses were seen in 36 percent (8/22) of evaluable patients (95% confidence interval [CI]: 0.17–0.59), including 29 percent of patients (4/13) who were found to have the T790M mutation.  Updated data will be available during the poster presentation at ASCO.  The study has since been expanded to enroll 80 patients; results will be presented at a future conference.(1)  

Boehringer Ingelheim will also present data at the ASCO annual meeting from several additional studies evaluating afatinib in patients with NSCLC, brain metastases and glioblastoma, and other advanced solid tumors.

About the ASCO Provisional Clinical Opinion and NCCN Clinical Practice Guidelines

Based on the growing body of research, ASCO issued a provisional clinical opinion in April 2011 stating that patients with NSCLC who are being considered for first-line therapy with an EGFR TKI should have their tumor tested for EGFR mutations to determine whether an EGFR TKI or chemotherapy is the appropriate first-line therapy.(3) Earlier this year, NCCN updated its clinical practice guidelines to include a category 1 recommendation for EGFR testing after a histologic diagnosis of adenocarcinoma, large cell carcinoma or undifferentiated carcinoma.(4)

It is believed that approximately 5-20 percent of NSCLC patients have mutations of the EGFR tyrosine kinase, with an increased frequency in patients with adenocarcinoma, Asian ethnicity and former/nonsmoking status.(5,6)

About Afatinib

Afatinib is an investigational compound.  Afatinib is not approved by the FDA; its safety and efficacy have not been established.  

Afatinib is an orally-administered irreversible inhibitor of the erbB family of receptor tyrosine kinases, specifically EGFR and HER2.  It is in late-stage development in several solid tumors including advanced NSCLC and breast cancer.  

About the Afatinib Clinical Program

Boehringer Ingelheim is actively developing targeted therapies – biologicals and small molecules – in areas of unmet medical need. This includes both solid and hematological cancers.  The company's comprehensive LUX clinical trial program includes, among other trials, more than 10 registration trials investigating afatinib for potential approval for a variety of solid tumor types, including NSCLC, breast and head and neck cancer.  

LUX-Lung 1 was a phase IIb/III trial investigating afatinib plus best supportive care (BSC) versus placebo plus BSC in NSCLC patients who were previously treated with first-line chemotherapy and the reversible EGFR TKIs erlotinib or gefitinib.

LUX-Lung 2 is a phase II trial evaluating afatinib in NSCLC patients with EGFR mutations, either treatment naïve or after one line of chemotherapy.

Boehringer Ingelheim recently completed enrollment in the phase III LUX-Lung 3 trial that will specifically investigate afatinib as a first-line treatment in patients with advanced NSCLC with EGFR mutations.  Another ongoing phase III trial, LUX-Lung 6, also investigates the efficacy and safety of afatinib compared to standard chemotherapy for first-line treatment of NSCLC patients with EGFR mutations in different geographical regions.

LUX-Lung 4 is a phase I/II trial of afatinib in NSCLC patients who have progressed after conventional EGFR-TKI treatment.  

LUX-Lung 5 is a global phase III trial in patients previously treated with erlotinib or gefitinib. This is the first randomized phase III trial investigating whether patients who initially benefit from treatment with afatinib alone may further benefit from afatinib beyond progression when given in combination with chemotherapy.

About Lung Cancer

Lung cancer is the second most common cancer and kills more people than any other cancer. In 2010, approximately 222,520 new cases of lung cancer were diagnosed in the United States, with 157,300 Americans dying from the disease.  NSCLC is the most common form of lung cancer, accounting for about 85 percent of all lung cancers.(7) Lung cancer remains an area of high unmet need, especially in its advanced stages where it is particularly aggressive and patients have limited treatment options.

About QIAGEN

QIAGEN is the leading global provider of sample and assay technologies. Sample technologies are used to isolate and process DNA, RNA and proteins from biological samples such as blood or tissue. Assay technologies are used to make such isolated bio-molecules visible. QIAGEN has developed and markets more than 500 sample and assay products as well as automated solutions for such consumables. The company provides its products to molecular diagnostics laboratories, academic researchers, pharmaceutical and biotechnology companies, and applied testing customers for purposes such as forensics, animal or food testing and pharmaceutical process control.  QIAGEN's assay technologies include multiple companion diagnostics that are co-developed with its pharmaceutical partners. Companion diagnostics are used to predict in advance which patients are most likely to benefit from a particular therapy.

QIAGEN's portfolio encompasses the therascreen® EGFR RGQ PCR Kit (CE-IVD) available in Europe, as well as a broad panel of other biomarkers including KRAS, PI3K, BRAF for Research Use Only (RUO) or CE-IVD. The QIAGEN EGFR test is not available for routine clinical diagnostic use in the United States.

QIAGEN employs nearly 3,600 people in over 30 locations worldwide. Further information about QIAGEN can be found at www.QIAGEN.com.

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.

In 2010, Boehringer Ingelheim posted net sales of approximately $16.7 billion (about 12.6 billion euro) while spending almost 24% of net sales in its largest business segment, Prescription Medicines, on research and development.

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

References

1. Janjigian YY et al.  Activity and tolerability of afatinib (BIBW 2992) and cetuximab in NSCLC patients with acquired resistance to erlotinib or gefitinib.  Abstract 7525, poster presentation at 2011 Annual Meeting of the American Society of Clinical Oncology, Chicago, June 6, 2011.  
2. Sharma SV et al. Epidermal growth factor receptor mutations in lung cancer.  Nat Rev Cancer. 2007;7(3):169-181.
3. Keedy V et al.  American Society of Clinical Oncology Provisional Clinical Opinion: Epidermal Growth Factor Receptor (EGFR) Mutation Testing for Patients With Advanced Non–Small-Cell Lung Cancer Considering First-Line EGFR Tyrosine Kinase Inhibitor Therapy.  J Clin Oncol. 2011 April.
4. National Comprehensive Cancer Network.  Non-Small Cell Lung Cancer Clinical Practice Guidelines.  January 2011.
5. Riely GJ et al.  Clinical course of patients with non-small cell lung cancer and epidermal growth factor receptor exon19 and exon 21 mutations treated with gefitinib or erlotinib.  Clin Cancer Res. 2006 Feb 1;12(3 Pt 1):839-44.
6. Gazdar AF.  Activating and resistance mutations of EGFR in non-small-cell lung cancer:  role in clinical response to EGFR tyrosine kinase inhibitors. Oncogene. 2009;28(suppl 1):S24-S31.
7. American Cancer Society. Cancer Facts and Figures: 2010. Available at: http://www.cancer.org/acs/groups/content/@epidemiologysurveilance/documents/document/acspc-026238.pdf. Last accessed Dec. 3, 2010.

SOURCE Boehringer Ingelheim Pharmaceuticals, Inc.