Originally published June 13.
By Turna Ray
Agendia will deploy its ColoPrint colon cancer recurrence test in a collaboration with MD Anderson Cancer Center and the Netherlands Cancer Institute intended to further understand the molecular pathways driving the disease. The study will also yield additional validation data on ColoPrint that, if positive, will likely bolster the regulatory and reimbursement prospects for the test in the US.
As part of the project, "Agendia will perform gene expression analysis on colon cancer samples of known clinical outcome from MD Anderson cancer center to validate the ColoPrint signature," a company representative told PGx Reporter.
The broader objective of the collaboration between the three entities is to employ multiple genomic and proteomic analysis methods to uncover the pathways driving colon cancer subtypes and the molecular mechanisms behind differential response to treatments.
"We will use multiple 'omics' technologies to ask which kinase signaling pathways are activated in colon cancer," the Agendia spokesperson said last week, following the announcement of the collaboration.
Within the partnership, the Netherlands Cancer Institute will perform exome sequencing of the kinome of hundreds of tumor samples that MD Anderson will provide. In these same samples, MD Anderson will use reverse phase protein lysate array technology to analyze activated kinases. Agendia's role in the study will be to perform gene expression analysis with ColoPrint.
Knowledge of the major driver pathways in colon cancer will "enable patient-tailored treatment regimens for individual colon cancer patients," the Agendia representative said.
Using these various genomic and proteomic analysis methods, the Netherlands Cancer Institute, MD Anderson, and Agendia will characterize each tumor sample by gene expression, gene mutation, and protein activation. Researchers will then combine this data with patients' pathological and clinical data.
This is the second partnership Agendia has formed in the past month around colon cancer. In mid-May, Agendia entered the companion diagnostics space for the first time, signing a deal wit AstraZeneca and the Netherlands Cancer Institute to apply its diagnostics capabilities to accelerating the development of targeted colon cancer drugs. Under the deal, it is also possible that Agendia will develop commercial companion diagnostics for specific drugs in AstraZeneca's pipeline (PGx Reporter 05/11/2011). It is unclear if ColoPrint will be used in this Rx/Dx partnership.
Agendia is in the final development stages for ColoPrint, an array-based gene expression profiling test for predicting the risk of distant recurrence of stage II and III colon cancer patients. Agendia plans to submit the test to the US Food and Drug Administration for approval but has not disclosed a timeline for doing so.
Two years ago at the American Society for Clinical Oncology's annual meeting, Agendia presented data from the study through which it developed the gene expression signature underlying the ColoPrint test. In the study, a research team from Agendia and other research institutions in the Netherlands found that ColoPrint was able to "predict the prognosis of stage II and III colon cancer patients and facilitate the identification of patients who would benefit from adjuvant chemotherapy."
Researchers used Agilent 44K oligonucleotide arrays to analyze frozen tissue samples from 180 Stage I-III colon cancer patients undergoing surgery. Based on full-genome expression measurements, the study authors classified patients into three molecular subclasses: A, B, and C (PGx Reporter 02/03/2009).
Survival analysis showed that 27 patients in subclass C had poor outcome, while 48 patients in subclass A had good outcome. The researchers used data from 104 subclass B patients (the intermediate group) to develop a gene signature associated with five-year distant metastasis free survival.
This gene signature was validated in 178 tissue samples from patients with Stage II and Stage III colon cancer, who were followed for almost six years. At five years, 90 percent of patients classified as low risk by ColoPrint and just over 60 percent of high-risk patients had survived disease-free.
At this year's ASCO meeting, researchers from Agendia and several other European institutions provided an update on the Prospective study for the Assessment of Recurrence risk in Stage II colon cancer patients, or PARSC, involving the 18-gene expression profile test. PARSC began in September 2008, including 26 participating sites in 11 countries, but is still attempting to recruit a large enough patient cohort to yield significant results.
The aim of the study is to validate the ability of the ColoPrint profile to pick out which patients will relapse within three years compared to risk assessments conducted using clinical parameters and ASCO's recommendations for high-risk stage II patients.
So far, out of 262 stage II patients, 214 are eligible for evaluation. Researchers plan to launch an interim analysis after 300 eligible stage II patients have been enrolled. Approximately 600 stage II patients are needed to differentiate with statistical significance between three-year recurrence-free survival predicted by ColoPrint and clinical factors.
ColoPrint is marketed in certain European markets with a CE marking. Agendia recently filed to go public in Europe. The company hopes to raise around €81.4 million ($119 million) in the IPO.
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