Genomics for identifying tumor-related molecular pathways have long been pharma and biotech sponsors’ chief investigative focus for capturing unique patient and tumor characteristics in the pursuit of custom oncology treatments. Now, transcriptomics and analyses of the tumor microenvironment are assuming greater importance, with a view toward improving target agent penetration and efficacy.
As a result, the most efficient approach to more predictive biomarker assessment is a multifaceted one. A successful precision medicine strategy hinges on access to a variety of innovative, customizable testing capabilities supported by advanced application expertise, proactive management and impeccable, flexible execution across geographies.
Biomarker success relies on the interplay of key technologies
Multiple techniques used in oncology clinical research, such as flow cytometry, spatial omics, genomics and multiplex IHC, must work in synergy to address a given scientific question and shorten the timeline to better oncology trials and therapies. The concerted effort needed to make the best use of these modalities requires a high degree of organization.
“Specialized laboratories or all-under-one-roof centers of excellence in areas such as immuno-oncology help ensure project success,” says Jérôme Sallette, CSO at Cerba Research. “Global co-location of technical and scientific experts facilitates collaboration to meet sponsor-specific needs with suitable flexibility and customized validation.”
Flow cytometry, whether for immunophenotyping, receptor occupancy, immune cell activation or pharmacokinetics in CAR-T trials, or minimal residual disease (MRD) testing, typifies the benefits of collaboration. Scientist-to-scientist conversations during study design and at study startup allow multi-specialist providers to tailor test panels judiciously and validate them in a timely manner. Challenges should be addressed proactively. For example:
- Sample integrity may be supported through a global network of processing labs that standardize sample preparation (e.g. PBMCs).
- Limited sample volume can generate more data with the help of spectral flow cytometry.
- Flexibility to scale up rapidly in response to variable patient recruitment across the globe may be facilitated by a system for harmonizing and standardizing data analysis and review, regardless of geographic source.
Spatial omics also demonstrates the benefits of dedicated, in-house expertise and capabilities. Scientists can give guidance for the most appropriate panels and morphology markers while collaborations with our pathologists will help define the most relevant regions of interest. Combined histopathology and genomics experts and labs can provide both research and exploratory solutions. Key technologies enable characterization of the tumor microenvironment through RNA sequencing and protein analysis at spatial resolution. Such knowledge has become essential in precision medicine.
For holistic insights, flow cytometry and spatial omics are ideally complemented with additional capabilities. These may include genomics, IHC, molecular techniques like quantitative polymerase chain reaction (qPCR) and droplet digital PCR (ddPCR), new serological assays or multiplex ligand binding assays (LBA). A provider with the know-how to validate new assays and merge all these techniques with experience-based intention is invaluable and positions clinical research teams for success in the fast-growing field of cell and gene therapy, where customization, validation and standardization are key.
With increasingly complex clinical trials, sample integrity and value chain issues are magnified
As the science governing clinical research becomes more complex, with various techniques being applied in combination, every clinical sample is expected to yield maximal data.
“The challenge in reliably producing such data extends beyond technologies and scientific expertise,” Mr. Sallette explains. “It encompasses the entire value chain. Sponsors, from large pharma companies to biotech startups, must consider operations, preanalytical procedures, quality and flexibility carefully when choosing a multi-specialist provider.”
With biomarker development, increasingly complex and multi-technique assays demand more elaborate and customized kit building. With the expectation of diverse downstream analyses, integrity-preserving sample collection and handling, processing and logistical modalities become even more crucial. Smooth operations require sophisticated project management with open sponsor communications to achieve the necessary level of flexibility and to address evolving needs.
A provider that can cover the full spectrum from research through clinical and IVD trials, with capabilities for medical testing, sample collection and data at a very large scale, offers benefits throughout the value chain. Broad capabilities not only aid in the development of new drugs and new assays, but also assist with downstream real-life implementation for patients in diagnostics settings.
Indeed, a partner’s ability to advise on suitable test design and, in some cases, simplification, may improve patients’ access to the drug or test once marketed.
How complex oncology trials have become: three illustrations, including CAR-T
While the synergy of key technologies can provide scientific insights likely to yield more targeted biomarker strategies, it’s important to comprehend how demanding these trials can be. The practical importance of selecting a multi-specialist provider with appropriate expertise and capabilities is worth considering. To illustrate, here are a few examples of recent projects Cerba Research has undertaken:
- CAR-T cell therapy trials demand a variety of techniques as well as assay development. In one such trial, the team needed to custom-design, validate and then mobilize highly complex flow cytometry panels. In addition, they had to implement high-resolution NGS testing for human leukocyte antigens (HLA), multiplex cytokine panels and custom-designed replication-competent retrovirus/lentivirus (RCR/L) testing in qPCR — alongside more classical lab testing. With so many studies, care to maintain sample integrity was paramount. Pre-analytically standardized sample processing, particularly for peripheral blood mononuclear cells (PBMC) isolation, and bone marrow aspirates (BMA), was essential to ensure success.
- Another case involved global trials in more than 60 countries. Cerba Research needed to mobilize its worldwide logistics network to collect and process PBMC and BMA samples for cell sorting and isolation. They then had to conduct highly complex fluorescence in situ hybridization (FISH) studies at global scale in several laboratories.
- Another CAR-T study included flow cytometry, immunohistochemistry and multiplex cytokine panels. At the same time, the team had to manage complex logistics with cryopreserved samples, performing most of the tests in-house on two continents while also managing more than five referral labs.
With this much complexity, many things can go wrong. As indicated above, ensuring and standardizing sample integrity is key to correctly validating a new biomarker. “Without sample integrity,” Mr. Sallette points out, “output from the most advanced analytical technologies will be meaningless.” He adds, “Extensive validation with the right samples and the right expertise is very demanding. This is especially true with respect to timelines and obtaining the desired degree of precision, variability and specificity.”
Additionally, for a truly actionable global footprint, harmonization and standardization are essential. Furthermore, the assay must be designed in compliance with relevant quality and regulatory standards, especially if it is to be used for patient recruitment or, in the future, as a diagnostics or companion test. A failure in any of these details can derail a project.
A single, multi-specialty provider with the management capabilities and expertise to handle an entire study can simplify complex requirements.
Pharmaceutical and biotech sponsors, e.g. in oncology, rare diseases or infectious diseases, require a research partner that makes it easier to apply the multi-faceted oncology toolkit needed for success in the current research environment. From exploratory biomarker development to IVD kit building — one partner that can run the whole study, everywhere, expertly, is preferable to trying to coordinate the work of multiple providers. A suitable all-round provider will help sponsors save time, effort and cost with experienced guidance and streamlined systems in place that promote efficiencies and avoid errors.
The most suitable multi-specialty provider will offer flexible and innovative approaches for biomarker development, with attributes such as:
- Variety of dedicated resources for implementation and validation of new biomarkers: Sponsors benefit from the partner’s extensive experience and expertise with state-of-the-art instrumentation for modalities such as flow cytometry, spatial omics, genomics and multiplex IHC as well as customized NGS panels.
- Culture of collaboration and transparency: For successful strategizing and execution of customized, state-of-the-art strategies for targeted or broad approaches to biomarker selection, collaboration is key. The partner’s organization should facilitate interactions and transparency among provider scientists and between the sponsor and provider teams.
- Global network of laboratories and data: Capacity, breadth and global reach resembling that of a central lab with high-quality testing capabilities provides added flexibility. In addition, global access to demographically rich clinical trial data and capabilities in sourcing qualified specimens helps ensure sponsors’ target timelines are met.
- Proven ability to execute strategies through harmonized processes: A globally harmonized system with consistent, company-wide SOPs and method-transfer and validation processes is essential and can save time, costs and improve accuracy. A dedicated bioinformatics team and an automated platform for managing and transferring data from diverse sources in a centralized, aligned format result can streamline data analysis.
Deep expertise, customized services and well-designed operations enable sponsors to optimize protocol development and obtain innovative, flexible solutions grounded in scientific insights.
A global multi-specialist innovates at the frontier of precision and predictive medicine.
In the fast-moving field of precision medicine, stasis is not an option. Over 40 years, Cerba Research has harnessed its heritage in specialty, diagnostic and central lab services to create a unique, multi-specialty approach to underpin the next generation of clinical and IVD trials. With centers of excellence in oncology, infectious disease, hepatology, and so on, and expertise in technologies, such as flow cytometry, histopathology, genomics, cell-based assays and ligand-binding assays, the company’s expertise in cell and gene therapy is growing rapidly.
With a single partner for all test services, sponsors receive regular access and consistent support across all clinical trial phases to realize the transformative, human-centric clinical research of tomorrow. Dedicated resources for implementation and validation of new biomarkers, combined with capabilities in sourcing qualified specimens, allow Cerba Research to provide flexible and innovative approaches for development of new, exploratory biomarkers and IVD kit products. Oncology and genomics clients obtain customized, innovative, flexible, global solutions grounded in scientific expertise and impeccable execution, shortening timelines to better oncology trials and therapies.
For a company, implementing new techniques and amassing expertise represent significant commitments. Addressing the business model and economical sustainability of each investment is essential, with partnership playing an important role.
“Being an innovative player in precision and predictive medicine is a daily requirement,” says Jérôme Sallette. “We are always screening the market for innovative technologies and knowledge. It also requires a lot of humility in an increasingly complex world where interactions, conversations, and mutual knowledge-sharing and collective intelligence are key for success.” At Cerba Research, working day after day to offer clients the most innovative approaches is a passion — to benefit patients, improve healthcare and make the world a better place.
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