By Diagnostics World Staff
May 4, 2016 | In separate announcements yesterday, Foundation Medicine released FoundationACT (Assay for Circulating Tumor DNA), and launched an agreement with AstraZeneca to develop companion diagnostic assays to facilitate personalized medicine in oncology by identifying patients most likely to benefit from medicines within AstraZeneca’s oncology pipeline.
“We use companion diagnostics throughout clinical development to deliver innovative, targeted therapies to patients most likely to benefit,” said Ruth March, VP and Head of Personalised Healthcare & Biomarkers at AstraZeneca, in a statement. “The leading genomic profiling approach provided by Foundation Medicine can help ensure that patients are matched with therapies specifically targeted to the molecular drivers of their disease.”
As part of the collaboration agreement, AstraZeneca will use the Quality Systems Regulations (QSR)-compliant version of Foundation Medicine’s comprehensive genomic profiling assay for solid tumors to enroll patients into clinical trials of therapies that target genomically-driven mechanisms of disease. The companion diagnostic assay assesses multiple cancer-related genes as well as all four classes of genomic alterations, and will be developed in parallel with the clinical development of AstraZeneca medicines as part of a coordinated regulatory strategy.
“This collaboration agreement, the fourth we have put in place with leading oncology companies, underscores the importance and potential of utilizing our rigorously validated, comprehensive profiling approach to make available to physicians an FDA-approved universal companion diagnostic solution for use with targeted medicines,” said Steven J. Kafka, Ph.D., President and Chief Operating Officer for Foundation Medicine. We look forward to providing further updates as individual programs are initiated.”
FoundationACT
The company also launched FoundationACT (Assay for Circulating Tumor DNA), an analytically validated and accurate blood-based circulating tumor DNA (ctDNA) assay. By analyzing circulating tumor DNA isolated from a patient’s blood, FoundationACT can identify clinically relevant genomic alterations and deliver a concise report that matches the findings with potentially relevant targeted therapies and clinical trials.
“Our goal has always been to deliver a highly accurate and sensitive assay available for blood based samples, and the confirmatory data produced by our clinical collaborators indicates that we have succeeded in achieving that with the release of FoundationACT,” said Vincent Miller, M.D., chief medical officer of Foundation Medicine in a statement. “Bringing the rigor used to develop and validate FoundationOne to this assay, we believe we have overcome many of the clinical limitations presented by other tests in the liquid biopsy field. Launching FoundationACT strengthens our market leading position as the go-to resource for a complete, end-to-end offering of comprehensive molecular information solutions.”
The presence of ctDNA, which is DNA shed from tumors that circulates in blood, is a well-established phenomenon that has led to the development of non-invasive tumor sequencing assays. However, the concentration of ctDNA compared to other DNA fragments derived from other tissue sources can vary significantly depending on tumor type and disease stage. For many cancer patients, this means that the proportion of detectable tumor DNA in the blood is extremely low, making the detection of therapeutically relevant genomic alterations much more difficult and error prone as compared to tissue-based approaches.
FoundationACT, which was launched to Foundation Medicine’s pharmaceutical partners for research use in December 2015, interrogates all clinically relevant alterations across 62 genes and fusions across six genes, and it has been optimized for sensitivity and specificity of all classes of molecular alterations, including base substitutions, insertions and deletion, focal amplifications and gene fusions. The assay was developed for patients who are not candidates for comprehensive genomic profiling with FoundationOne because of insufficient or inadequate tissue from a recent biopsy, safety risks associated with biopsy, or medical contraindications to re-biopsy.
In July 2015, Foundation Medicine initiated a large-scale, multi-center prospective clinical study to clinically validate FoundationACT across various cancers and stages of the disease. A portion of the patients in the study will include those with earlier-stage disease, allowing the company to investigate how different tumor types shed DNA into the bloodstream at different stages of the disease.
The company presented findings at the Annual Meeting of the Advances in Genome Biology and Technology (AGBT) in February 2016 and the American Association of Cancer Research Annual Meeting in April 2016. The study found that FoundationACT results were 100% concordant with FoundationOne and droplet digital PCR (ddPCR) results across 87 base substitutions (43 at <5% MAF), three indels and five genomic alterations. The company reports ≥99% sensitivity in the detection of alterations present in blood at low frequency with a very low rate of false positives, realizing the potential of ctDNA-based molecular profiling for the management of patients with cancer. In 48 clinical ctDNA samples, 95 alterations of all classes were 100 percent confirmed by orthogonal testing.