Advancing your global companion diagnostics program: Insights from a recent Japan symposium (Part 1)
Through companion diagnostics (CDx), a patient can receive individualized treatment designed to improve clinical outcomes while avoiding adverse effects. A key component of precision medicine, CDx can also lead to significant cost savings, cutting up to 60% of the total clinical trial research and development costs. The global CDx market thus has been growing rapidly and is estimated to reach USD 17.6 billion by 2027. It is crucial for companies developing CDx programs to choose a partner with the right capabilities and experience, especially with validations required for approval from regulatory bodies, such as the FDA. Our experience supporting successful CDx clinical trials globally has helped us gain deep insights into CDx development best practices.
The ideal model for going from basic research to FDA approval is the co-development of a prescription (Rx) drug and its associated CDx. However, at a recent symposium, Dr. Chang-Jun Yue, global medical director at Labcorp’s Los Angeles lab, noted how rare it is for pharmaceutical companies to achieve Rx/CDx co-development. Fortunately, there are alternative pathways to the co-development route, which Dr. Yue discusses in his presentation. He also discusses the various types of submissions for FDA approval and the related validation parameters and standards. Read on to discover more insights from Dr. Yue’s presentation, where he also explores the crucial considerations that can help advance global CDx programs—namely, antibody and tissue selection, cutoff design, and finding the right IVD partner.
FDA’s criteria for approving IVDs and LDTs
The parameters for FDA approval are designed to ensure safety and effectiveness. A safe device is one whose probable benefits outweigh the probable risks. An effective device is one that will provide clinically significant results. In vitro diagnostics (IVDs) require clinical and analytical validation, while laboratory-developed tests (LDTs) require only analytical validation.
For clinical validation, the clinical cutoff is the most important component. Lowering cutoffs allows pharma companies to include more patients, which can significantly expand the number of patients who may ultimately be eligible for the treatment when approved. Alternatively, increasing the cutoff decreases the number of patients and can reduce risk, but it also decreases the potential pool of eligible patients. An optimum clinical cutoff can ensure the right balance between risk and market opportunity.
Important considerations for your CDx program
Some important questions must be considered when selecting the right antibody during the validation process. These questions should address whether to use monoclonal or polyclonal antibodies, which type of animal to use for antibodies based on the specificity, whether to use commercial or proprietary antibodies, and whether the suppliers are stable. Dr. Yue discusses his specific recommendations for each of these considerations. When multiple options are available, Labcorp subject matter experts can assess them to advise you on what may best meet your needs.
When it comes to tissue selection, optimization is critical. Setting the baseline with normal tissues rather than tumor tissues is generally recommended. Additionally, it is important to consider that the number of samples to use for validation based on requirements from the College of American Pathologists (CAP) or FDA may vary.
Another important question for CDx programs regards cutoff design. For very new markers or antigens, it is recommended to start with data from surveys on purchased tumor samples. Notably, some of the phases of clinical trials involve trial and error, so the cutoff can be adjusted in later phases. Deciding on a higher or lower cutoff determines your risk and gain balance.
When it comes to selecting the right IVD partner, some considerations may be more important than financial ones. Understanding your partner’s strengths and their team’s experience becomes crucial as you rely on their scientists and pathologists to design your CDx program. Partners also have different platforms, and those offering reliable and clear staining should be prioritized. Labcorp’s global project management and experienced lab teams have consistently delivered reliable solutions to support CDx programs.
A central pathology review is essential for the FDA submission process. Selecting a central lab that monitors data integrity with established QA and QC processes is crucial for the central pathology review process. To ensure consistency in data presented for review, the FDA requires the data to be collected from a central lab and not from hospitals. Notably, the FDA accepts complete pathological response as the endpoint for accelerated drug approval. Complete pathological response occurs when a drug is successful in eliminating tumor tissue entirely prior to surgical removal of tissue. The trend of the FDA assessing drugs via complete pathological response started with drugs that targeted breast carcinomas, which was later adapted for other organs. Labcorp’s Los Angeles lab was one of the first to work on non-breast tumors.
Our experience supporting CDx clinical trials
The CDx validation process comes with major challenges, underlining the importance of leveraging an experienced partner. Labcorp has conducted over 1,000 oncology trials across various tumor types and supported over 700 trials in CDx development. We have supported over 60% of the total and over 85% of PD-L1 CDx applications approved by the FDA each year.
Some success stories from our Los Angeles lab:
- First to validate the PDL-1 and make the IVD kits available
- Performs 40% of Labcorp’s CDx studies (about 160 per year)
- Ran 44 CDx and 23 non-CDx studies in 2023
- One of the first central labs to perform complete pathological response
With our four core central lab teams—DDS management oversight, core project team, functional support, and laboratory team—we work with you to efficiently support your CDx clinical trials.