There has been a real revolution in the understanding of molecular biology. This revolution is fueled by the rapid decline in the costs of sequencing, which allowed next-generation sequencing (NGS) assays, previously only seen in research laboratories, to begin making inroads into molecular diagnostics. The wide-ranging capabilities of next-generation sequencing offer extraordinary opportunities for the development and new companion diagnostics to probe oncogenes, tumor suppressor genes and cancer-enabling genes.[1]

Based on the explosive increasing in knowledge and understanding caused by the availability of new diagnostic tests, scientists are now changing the way they are thinking about diseases such as cancer. A better appreciation of genetic differences found in patients and their tumors, has helped explain the variability and difference in the response to specific treatments of cancer.

…companion diagnostic tests are playing a central role in delivering on the promise of personalized medicine…

While many diseases, including cancer, may, on the surface, seem the same, the increased understanding of molecular biology has helped scientists to appreciate that these diseases, on a molecular basis, can be fundamentally different.</>

A new approach
Before the dawn of personalized, targeted therapies, most cancer patients with a specific type and stage of cancer often received the same or similar treatment. While some patients benefited from these treatments, many patients did not or benefited only slightly.

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Today, many patients may still receive a more-or-less standard treatment for a specific form of cancer (which may include surgery, radiotherapy, chemotherapy or other interventions). But physicians can now also ?personalize? treatment based on an individual patient?s genetic profile.

A key to success
Understanding the unique molecular characteristics of an individual patient is key to the success of personalized medicine. It offers physicians the ability to determine a patient?s unique molecular characteristics and to use the genetic distinctions to diagnose more precisely the patient?s disease and select appropriate treatments based on these molecular characteristics that increase the chances of a successful outcome, while reducing the potential for possible adverse reactions.

Drug development and diagnostics
To be successful, these personalized cancer treatment ? tailored to the individual patient ? requires the collaboration between drug development and diagnostics. They may be offered as an active part of the treatment or as part of a new or ongoing clinical trial.

Companion diagnostics
To understand which patients would benefit from a particular drug or therapy or, conversely, which patients do not ? and as a result should not receive a particular medication, a number of medical device manufacturers are developing tests called ?companion diagnostics.?

In short, these ?companion diagnostics? are medical devices designed to help physicians decide which treatments they should or shouldn?t to offer to individual. Today, these companion diagnostics are becoming more essential to the safe and effective use of specific drugs. Companion diagnostics can predict response to specific chemotherapy drugs and/or regimens. The expectation is that this will ? in time ? fundamentally change medicine, since treatment is often given in a ?one size fits all? approach rather than being tailored to the specific needs of the patient.

According to the American Society of Clinical Oncology(ASCO), future cancer therapies will be developed through molecular approaches that can accelerate development of more effective, personalized treatments. Identifying specific genetic characteristics of malignancies is expected to also support development of new treatments that target specific proteins involved in the development and growth of cancer.

Development of new companion diagnostics
Earlier this week, Ventana Medical Systems, Inc, a member of the Roche Group involved in the development of companion diagnostics to identify the patients most likely to respond favorably to specific therapies, announced that it has entered into an agreement withImmunoGen, Inc.a company developing targeted anticancer therapeutics, to collaborate on the development of biomarker assays and a companion diagnostic immunohistochemistry (IHC) test for one or more of ImmunoGen?s product candidates.

The first product with ImmunoGen?s ADC technology was ado-trastuzumab emtansine (Kadcyla?; Genentech/Roche)

As part of this new agreement between Ventana and ImmunoGen, the companies created an initial test for folate receptor alpha (FR?, also known as folate receptor 1, or FOL1) that is being used in early trials of IMGN853.

IMGN853, an antibody-drug conjugate or ADC currently in dose-finding Phase I clinical testing, is a potential new treatment for FR?-positive solid tumors ? which include many ovarian and endometrial cancers, as well as non-small cell lung cancer (NSCLC) and other cancers that highly express FR?. The drug is now being evaluated in a first-in-human study to evaluate safety, tolerability, pharmacokinetics and pharmacodynamics. The primary outcome of this study is to determine the Maximum Tolerated Dose (MTD) and recommended Phase II trial dose.[2]

In this drug, ImmunoGen?s FR?-targeting antibody is attached to the potent cancer cell-killing agent DM4. The antibody serves to target the compound specifically to cancer cells expressing FR?, and the maytansine analog DM4, a potent microtubule-targeted compounds, inhibit proliferation of cells at mitosis.

The goal of the collaboration is to leverage Ventana?s expertise delivering patient stratifying diagnostic tools that help identify individual patients and patient poulations who are most likely to benefit from ImmunoGen?s bio-target directed therapies.

Ventana will develop the companion diagnostics, from initial development and prototyping through regulatory approval and commercialization.

?Companion diagnostic tests play a central role in delivering on the promise of personalized healthcare,? said Doug Ward, Vice President, Ventana Companion Diagnostics. ?[?] this agreement with ImmunoGen [?] further expand our menu of companion diagnostic test offerings for our pharma and biotech collaborators to benefit patients.?

?Our antibody-drug conjugate experimental therapies are designed to hone in on specific targets found on patients? cancer cells,? noted Charles Morris, M.B., Ch.B., M.R.C.P.. Executive Vice President and Chief Development Officer at ImmunoGen. ?Companion diagnostics can play an important role in ensuring the patients receiving our agents are ones with the targets and thus the patients most likely to benefit from the treatment. Having this collaboration with Ventana in place now helps us make sure the right patients are receiving IMGN853 during its development.?

For more information:
[1] Lin E, Chien J, Ong FS, Fan JB. Challenges and opportunities for next-generation sequencing in companion diagnostics. Expert Rev Mol Diagn. 2014 Sep 24:1-17.[Article][PubMed]
[2] First-in-Human Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of IMGN853 in Adults Wit
h Ovarian Cancer and Other FOLR1-Positive Solid Tumors (IMGN-0401)[Study Record Detail: NCT01609556]

This article was first published online in ADC Review / Journal of Antibody-drug Conjugateson October 28, 2014.

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