3 Central Lab Capabilities Mandatory for I/O Clinical Trial Success
In the exploding field of immuno-oncology (I/O), delivering the right treatment to the right patient at the right time requires expert, integrated clinical laboratory and diagnostic solutions delivered by top scientists who will help you assess needs and generate early insights that optimize your protocol. Along with access to a sizable patient database, impeccable performance across the globe, and I/O experience, three main testing capabilities are nonnegotiable when selecting a lab partner for the challenging journey from translational research to commercialization.
Biomarkers make all the difference in immunotherapeutic and personalized medicine
For a drug developer, the value of obtaining early biological insights that help identify the right patients, treatments, dosages, and durations and streamline complex trials cannot be overstated. Biomarker development and validation are key to:
- Guide dose selection
- Characterize mode of action or resistance
- Stratify patients/determine inclusion-exclusion
- Predict drug efficacy and safety profiles
- Aid in prognosis
- Monitor disease
At Cerba Research, where half of our studies are in oncology, access to biobanked human specimens provides a clear advantage when identifying novel and existing I/O-related pathways including tumor morphology, tumor genetics, tumor protein and gene expression, and tumor infiltrating lymphocytes (TILs). Related biomarkers can then be developed further to stratify patients into treatment groups, gauge efficacy, formulate hypotheses, and increase the trial’s probability of success.
3 types of test support a wide variety of biomarkers
For precision medicine in immuno-oncology, a complete program enabling a 360˚ view of patient status and tumor susceptibility demands experienced guidance and customization for three types of testing: flow cytometry, tissue immunohistochemistry (IHC), and genetic screening (next-generation sequencing, NGS).
Flow cytometry is a powerful technique that rapidly detects and measures thousands of cells with high sensitivity and specificity, providing a snapshot of the immune response. Beyond cell surface markers, flow cytometry can also detect intracellular antigens such as cytokines and phosphorylated signaling proteins. This methodology allows functional analysis and helps with therapeutic strategies and prediction of therapeutic response. The simultaneous use of many biomarkers generates data that is multifaceted, highly complex, and dimensional.
Immune profiling by flow cytometry produces a large amount of information from a single blood sample. The result is a very granular breakdown, for example, of lymphocytes and subtypes, down to T cell memory subsets and activated-versus-nonactivated markers. Clinical researchers can utilize this technology to understand how patients are responding and what kind of therapies are suitable for patient-specific treatment plans.
These studies demand highly skilled staff scientists to develop and validate both off-the-shelf and novel biomarkers. Therefore, the lead time for assay development to validation must be considered. Further, for global trials, a standardized approach is critical, including instrument standardization and assay process standardization (same SOP).
Immunohistochemistry (IHC) is a cost-effective assay that profiles tissue biomarkers to individualize a patient’s therapy. It is an antibody-mediated approach that allows detection of the target of interest in the tissue through fluorescent or chromogenic revelation for quantification and cellular localization. This technique has typically been used for the diagnosis and classification of tumors such as lymphomas and breast cancer. In addition, IHC conveys structural information about the tumor and the tumor microenvironment, demonstrating the localization of immune cells in relation to the tumor or other immune cell populations. It can also reveal the expression of activation/deactivation biomarkers as part of immune cell profiling and oncogene evaluation. Cerba Research offers sponsors an ever-increasing number of novel I/O biomarkers, including hard-to-develop, customized IHC assays for the preclinical phase, with subsequent validation for use in clinical trials.
Multiplex IHC, the combination of several biomarkers on a single slide/section, is an advanced version that allows for the detection of up to eight biomarkers in one precious tissue section. The ability to detect more biomarkers per slide is increasingly important as:
- Demand for more biomarkers is growing.
- Accurate phenotyping requires several markers.
- Biopsy size limits the number of sections.
- Some data cannot be obtained from circulating markers, such as spatial context and organization and distances between populations of cells.
NGS for genetic screening
Genetic screening measures changes in nucleic acid sequences associated with disease susceptibility or resistance. Next generation sequencing (NGS) enables a wide range of new applications and investigations in genetics, including analysis of solid and hematologic tumor genomes as well as in-depth analysis of the patient’s immune repertoire pre- and post-treatment, including T cell receptor (TCR) analysis.
Cerba Research’s capacity for high throughput, with the ability to sequence 1,000+ whole human genomes in a week — coupled with one of the largest catalogs of clinical NGS genetic and genomic testing — helps ensure that sponsors reach milestones and preserve development timelines, whether they need whole exome sequencing or gene panels customized to suit their protocol.
Applications of genetic insights to look for:
- Biomarker discovery, with comprehensive genomic profiling and customized assays that link mutation to disease
- Prospective patient stratification screening with NGS, PCR, and other assays
- Companion diagnostics development on NGS-based or CHIP-based multiplex qPCR platforms to assess therapeutic suitability
- Cyto- and molecular-genetic diagnosis of constitutional and acquired disorders, including developmental disease, predisposition factors, and clotting malfunctions
As an example, the tumor mutational burden (TMB) is a genetic biomarker currently receiving some attention. Cancer is the result of a series of mutations, and cancer cell lines each have between one (1) and around 10,000 coding mutations, or .1 to 100 mutations per megabase — the tumor mutational burden. TMB is associated with antitumor response and is a good predictor of response to cancer immunotherapy drugs in some cases, such as melanoma, cutaneous squamous cell carcinoma, and certain colorectal and noncolorectal GI cancers. The reason may be that tumor cells with high TMB have high neoantigen loads, leading to greater T cell reactivity and an enhanced antitumor T cell response. Although the gold standard for TMB analysis has been whole exome sequencing, recent advances in NGS tumor panels have provided consistent results.
Support for immuno-oncology trials depends on experience and commitment
With ever-expanding possibilities for specificity and design, immune-based therapies are pouring into the clinical research funnel. In immuno-oncology clinical trials, finding the proper resources to achieve your goals can be a challenge. Three main testing methodologies are needed for immuno-oncology: multiplex immunohistochemistry (IHC) for solid tumors, flow cytometry for cells in suspension, and genetic studies (NGS).
Partnering with a high-performing global central lab like Cerba Research for patient- and science-driven insights can help you optimize your protocol, then seamlessly ramp up to commercial scale. You will be able to minimize expenditures while keeping timelines intact — and bring groundbreaking therapies to patients sooner. With over 35 years of experience, Cerba Research is a leader in immuno-oncology clinical trials, providing global solutions that include a vast array of biomarker assays and expert validation services. Start with Cerba Research. As your partner, we empower you to bring new life-changing therapies to patients worldwide.Together, we’ll change the shape of your clinical development.