Originally published July 29.
NEW YORK (GenomeWeb) – AstraZeneca is exploring the use of liquid biopsy-based companion tests to pick out best responders for its drugs for lung cancer, where acquiring biopsy tissue is particularly challenging for advanced patients.
The drugmaker this week announced two deals, one with Qiagen and another with Roche, to advance liquid biopsy-based companion diagnostics for its marketed non-small cell lung cancer drug Iressa (gefitinib) and the investigational NSCLC agent AZD9291, respectively.
AstraZeneca's Iressa is indicated as a first-line treatment for EGFR mutation-positive advanced NSCLC patients. The drug firm is also developing AZD9291, an irreversible inhibitor of EGFR that specifically targets the resistance mutation T790M. AstraZeneca is focused on advancing AZD9291 for patients who have become resistant to first-generation EGFR tyrosine kinase inhibitors, such as Iressa and Tarceva (erlotinib).
The deal with Qiagen to develop a companion test for Iressa will likely offer AstraZeneca quick market entry since the drug is not sold in the US, as well as test the viability of using circulating tumor DNA in a predictive setting.
"The test will be developed for the European market where Iressa is already approved, so a 510(k) is not needed," Thomas Theuringer, Qiagen's director of public relations, told PGx Reporter. In European markets, diagnostics developers can self register diagnostics via the so-called CE marking process ahead of test commercialization. Obtaining CE marking, according to industry players, is a less involved process than the US Food and Drug Administration's regulatory requirements for diagnostic pre-market approval or 510(k) clearance.
AstraZeneca, in 2011, pulled its accelerated approval application for Iressa in NSCLC, and said that it will not re-file a new application to try to launch the drug in a genetically defined subpopulation. The company said that after conversations with the FDA, it became clear that AstraZeneca wouldn't be able to meet the agency's requirements.
"Our intention is to register this diagnostic quickly [in Europe], making use of data sets and experience already gained in both AstraZeneca's and Qiagen's NSCLC portfolio of research and development," Theuringer said.
According to Qiagen, the liquid biopsy-based companion test is slated to become available on the market by next year. Data from published studies suggest that tissue samples aren't available or don't yield test results for between 10 percent and 30 percent of lung cancer patients.
The test for Iressa is initially intended to be used for NSCLC patients for whom tissue samples are not obtainable, but eventually, Qiagen envisions broader uses for blood-based companion diagnostics of this kind. "We have a growing portfolio of liquid biopsy solutions for personalized healthcare applications, and we see the potential for patient monitoring using blood tests for future Qiagen Therascreen CDx," Theuringer said.
At a recent medical conference researchers from AstraZeneca and elsewhere reported data from a post-marketing study of Iressa, showing strong concordance between tests that gauge EGFR mutations in tissue and plasma biopsies. In the Iressa Follow Up Measure study, researchers reported a post-treatment mutation rate of 13.7 percent in tumor samples and 10.5 percent in plasma samples. The concordance rate of EGFR mutation status between the two sample types was 94 percent.
The companion diagnostic AstraZeneca is developing with Roche, meanwhile, has a longer development timeline since AZD9291 is in the early stages of development. For this next-generation EGFR TKI, AstraZeneca is planning ahead in developing a companion test that can gauge mutations in both tissue and plasma samples.
Currently, patients whose lung cancer has progressed despite treatment with EGFR-TKIs have to undergo surgery to garner tissue for further molecular analysis. A test that can gauge circulating DNA in plasma samples would save advanced cancer patients from having to undergo invasive biopsies.
At the American Society of Clinical Oncology's annual meeting in June, AstraZeneca presented preliminary data showing promising activity of the agent, designed to more accurately target EGFR mutant cells and cause fewer side effects. A team led by Pasi Janne of Dana-Farber Cancer Institute evaluated nearly 200 patients in various dose escalation and expansion cohorts, and reported a 51 percent response rate with AZD9291 in all evaluable patients. Out of 89 patients with T790M mutations, 64 percent responded, while 23 percent of those without T790M mutations responded to AZD9291. Disease control was achieved in 85 out of 89 T790M-positive patients.
In this study, still being conducted, the longest enduring response was more than nine months, as reported in June. AstraZeneca did not respond to questions for this article ahead of press time.