INGELHEIM, Germany—Boehringer Ingelheim and DxS have partnered on a clinical trial to identify likely responders to new treatment for non-small cell lung cancer, the companies announced in June. Financial terms of the agreement were not disclosed.
Boehringer Ingelheim has chosen DxS as a partner because of the company's diagnostic kit for measuring mutations in the epidermal growth factor receptor (EGFR) in patients with lung cancer.
"We now wish to work together to adapt this kit for use in Boehringer Ingelheim's global multi-center, Phase III clinical trial of BIBW 2992 (Tovok) and ensure that the kit is available for the subsequent world-wide commercialization," says Dr. Manfred Haehl, corporate senior vice president of medicine at Boehringer Ingelheim. He adds that DxS is a company that is at the forefront of developing diagnostic solutions for personalized medicine.
BIBW 2992 is a novel tyrosine kinase inhibitor that acts by irreversibly blocking the EGFR/HER2 receptors, which are promoters of tumor growth. As with other tyrosine kinase inhibitor therapies, patients with mutations in the EGFR gene will be more likely to respond to a medication that targets these receptors, thereby allowing doctors to prescribe the most effective and individual treatment. Furthermore, BIBW 2992 has demonstrated preclinical activity against erlotinib- and gefitinib-resistant mutations. Neither of the latter two compounds blocks the target receptors irreversibly.
Clinical data published to date suggest that BIBW 2992 offers a marked increase in efficacy in comparison to standard treatments for lung cancer patients carrying mutations in the EGFR gene. The drug is currently in Phase III clinical development in non-small cell lung cancer (NSCLC). As epidermal growth factor receptor (EGFR) and human epidermal growth factor receptor 2 (HER2) play a pivotal role in many solid tumors, BIBW 2992 is also being investigated in other indications including breast, colorectal, head and neck cancers and glioblastoma.
To date, 409 NSCLC patients have been screened in the LUX-Lung 2 study and 104 patients with EGFR mutations have started treatment with BIBW 2992 once daily. Preliminary data were presented at ASCO 2009 for the first 73 second-line patients, all of whom had previously received one regimen of chemotherapy. Sixty-seven patients were evaluable for response. Interim data show that 64 percent of patients taking BIBW 2992 in the second line setting experienced a partial response, with 31 percent experiencing stable disease. Median progression-free survival (PFS) in the second line setting was 10.2 months.
The DxS EGFR companion diagnostic is a real-time PCR assay, designed to detect the most common mutations in the EGFR gene. The diagnostic has been developed and manufactured at DxS' head office in Manchester, UK., and will be available later in the summer for Boehringer Ingelheim's global, multi-centre Phase III clinical trial for BIBW 2992.
Commenting on this announcement, Dr. Stephen Little, CEO of DxS, says "This is another great endorsement of our companion diagnostic assays for predicting patient response to targeted therapies. It is an exciting step forward for personalized medicine and DxS is pleased to be at the forefront of this revolution in cancer treatment."
Little notes that there are two sets of hurdles to overcome in genetic testing when looking at tumor tissue rather than SNPs.
"When you're looking at tumors, the detection technique must work on the tumor biopsy where part of the sample is not tumor, but rather background," he notes. The second challenge is consistency: "In academic and other settings, 'home brews' don't have the necessary consistency. Our tests must work every time over 10,000 or even 100,000 samples," he states.
Privately held DxS has an expanding portfolio of cancer mutation products. Its TheraScreen range of CE-marked clinical diagnostic kits can identify genetic tumor mutations that affect how patients respond to cancer therapies, thus enabling doctors to provide the most beneficial treatment. DxS markets two clinical diagnostic kits, K-RAS and EGFR-29. The K-RAS Mutation kit is a companion diagnostic for Vectibix (Amgen) and Erbitux (Merck KGaA) for the treatment of colorectal cancer. DxS has an exclusive global distribution agreement with Roche Diagnostics for the distribution of its K-RAS and EGFR29 mutation kits.
