Radha Krishnan, MD | January 23, 2017

Fighting Cancer: Biomarkers for Immuno-Oncology Clinical Trials

Using anatomic pathology for biomarker development in clinical trials can help predict and assess how a patient will respond to IO therapies.
Each year, researchers and clinicians renew their determination to make a difference in the diagnosis and treatment of cancer on World Cancer Day.  This year’s campaign theme is “We can. I can.”—an appropriate slogan for a fight that truly does depend on everyone’s contribution. Each person, from donors and patients to scientists and doctors, has a role to play in reducing the global burden of cancer.

At Q2 Solutions, we’re attacking cancer from many angles, but one approach we’re particularly excited about is the use of anatomic pathology for biomarker development in clinical trials. This technology can help predict and assess how a patient will respond to immune-oncology (IO) therapies, which are some of the most promising new treatments clinicians have to fight cancer.

Using Anatomic Pathology to Develop Biomarkers

Biopsies taken for clinical evaluations can be particularly useful for biomarker development during IO clinical trials. Ideally, anatomic pathology biomarker development would utilize existing tissue biopsy samples, reducing patient burden and streamlining the research process. Tests would be straightforward in creation and interpretation, methods would be standardized across trial sites, and all biomarker assays developed for research would lead to beneficial, commercially available tests.

In reality, however, the process of creating and implementing a biomarker using anatomic pathology faces several key challenges.

Key Challenges to Biomarker Development in Clinical Trials

Programmed cell Death-Ligand 1 (PD-L1), a molecule expressed on tumor cells and inhibiting the anti-cancer immune response (hence refer to as immune check-point inhibitor) offers a great opportunity to examine the gamut of challenges facing biomarker development. Many studies across a diversity of tumor types have linked the pretreatment expression level of PD-L1 in the tumor microenvironment (in later stage patients) and the likelihood of response to single-agent PD-1 pathway inhibitor therapy. This makes it a high-priority candidate for assay development in clinical trials, leading to Key Challenge 1:

  1. Common biomarker, disparate assays. PD-L1’s potential as biomarker predictive of drug response is now well-known, and multiple assays are candidates for use in research examining anti-PD-1/PD-L1 therapies. Assay staining, visualization and scoring, thresholds for positive results, and the sample types needed to perform the assay can vary considerably, creating confusion over which assay to order and how to use it properly in research. This challenge is exacerbated by Key Challenge 2:
  2. Technical variability in sampling. In all clinical research using tissue samples, there are storage, transportation, and collection and processing techniques that impact the reliability and precision of the resulting assays. In IO trials, there are additional hurdles, such as tumor size, availability and age of tissue blocks, and adherence to specific immunohistopathology techniques. When variability complicates trial conduct, effective research is only further tested by Key Challenge 3:
  3. Operations and logistics of patient enrollment. Enrollment in studies may often hinge on ability of sites and laboratories to appropriately (and quickly) collect and process samples. Yet even when standards exist and protocols are explicit, enrollment can suffer due to unforeseen delays, regional differences in sample processing and preparation, import/export delays, and other difficulties.  

Demonstrated Assay Development and Trial Success

Well aware of these key challenges, Q2 Solutions recently used innovative and flexible laboratory solutions to help develop a PD-L1 immunohistochemistry assay in an early-phase study endeavor with a large pharma company. Forming a partnership with a major diagnostics company, Q2 Solutions developed immunohistochemistry test scoring methods, supported design control, and utilized the expertise of Q2 Solutions’ Anatomic Pathologist to make the early-phase work a success while also supporting late-phase research and commercialization. 

Q2 Solutions enabled the sponsor to obtain prototype tests for a wider range of indications and programs than what would have been available from the diagnostic company alone, with the potential to achieve enhanced commercial and revenue objectives. PD-L1 assays are now available for multiple sponsor programs, meeting performance requirements as well as documentation for future regulatory submissions.

Making Anatomic Pathology Matter for Worldwide Cancer Research

As part of an end-to-end biomarker plan for clinical trials, anatomic pathology can become an integral part of successful research outcomes for customers and patients. And when Q2 Solutions contributes thoughtful leadership and partnership to the process, we can help overcome the key challenges to biomarker development in IO research.

It is our belief that key research tools, like anatomic pathology, will help dramatically further the success of biomarker testing in IO trials, so that one day World Cancer Day won’t be about working toward new treatments—it will be about celebrating the cure. 

For more information, see Planning and implementing biomarker testing for immune-oncology trials.

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