The Future of Drug Development: The Implementation of Precision Medicine for Successful Oncology Drug Development
By Angela Qu, Senior Director, Biomarkers & Genomic Medicine, Parexel and Todd Shuster, Vice President and Global Therapeutic Area Head, Oncology/ Hematology, Parexel
Rapid progress in genomic sequencing, biomarker identification, data capture and analytics have helped to accelerate the adoption of trials that test precision medicines, including the use of genotyping and biomarkers, to identify patient groups likely to respond to a therapy by providing a more personalized approach to treatment.
Precision medicines now represent a significant and growing proportion of drugs in the industry pipeline, particularly in oncology where the majority of therapies in development are personalized. While precision medicine can be applied to the drug development process, it also has been shown to improve standard patient care through individually tailored treatment options depending on the unique genetic characteristics of a patient’s cancer.
Parexel commissioned the Economist Intelligence Unit (EIU) to assess how innovations like precision medicine can improve drug development for different diseases, such as cancer. Key findings from The Innovation Imperative: The Future of Drug Development demonstrated that implementing precision medicine in oncology clinical trials improved trial efficiency and increased the likelihood of drug launch.
Genetic mutations may lead to uncontrolled tumor growth, and a highly heterogenous disease like cancer not only yields differences between tumor types but can present differently from patient to patient within the same tumor type. With such irregularities of any given cancer type, there is a critical unmet need to develop personalized treatments to target a patient’s distinct genomic signature. The key to integrating such a personalized method is developing an early planning strategy to account for such a detailed approach. There are several considerations developed by Parexel when designing a precision medicine trial:
- Genomic information needed for optimized study design
- Inclusion criteria for an enriched patient population
- Genomic assays and technology for increased trial efficiency
Genomic Information for Optimized Study Design
A patient’s genomic information can help in targeting specific biomarkers when working to develop a strategy for clinical trials. Understanding the genomic makeup of a tumor allows physicians and researchers to implement therapeutic options tailored to an individual’s cancer profile. The traditional trial method of cancer treatment, matching a single therapeutic protocol to a single indication, is still widely used but is not the most sustainable approach for oncology. Because cancer genomic profiles may evolve over time and may consist of multiple mutations on multiple genes, a trial leveraging current genomic information may be more effective.
In contrast with traditional treatment regimens developed for a general tumor type, precision medicine treatment plans that target specific genomic or molecular aberrations are much more effective using clinical strategies such as basket or umbrella designs. A basket trial tests the effect of a targeted therapy on different types of cancer, all with one specific genomic aberration (i.e., tissue-agnostic), whereas an umbrella trial tests the effects of more than one targeted therapy in one type of cancer with more than one possible genomic aberration (e.g., EGFR, ALK, ROS, BRAF in NSCLC). Basket trials are particularly suitable in dealing with a rare mutation spread amongst a variety of tumor types, while umbrella trials may have a broader scope and require a longer duration to fully enroll all of the treatment cohorts.
Inclusion Criteria for Enriched Patient Populations
Adapting precision medicine enrichment strategies to recruitment allows researchers to refine which patients are more or less likely to respond to a treatment, thus improving the efficacy of a targeted therapy and the clinical trial efficiency. An enrichment study design enrolls only biomarker-positive patients to reduce the number of patients that are unlikely to benefit to a specific treatment plan. Having a study population that most readily demonstrates the effectiveness of a drug will increase the likelihood of being brought to market. While this strategy allows for a more responsive group of trial participants, enrichment plans can pose some barriers to adoption. These designs require a highly refined and detailed screening of candidates, which may result in increased time for enrollment of participants that meet the necessary criteria. Additionally, the lack of heterogeneity within the trial population poses a risk of missing other potential signals and targets for a different enrichment group. Therefore, other suitable patient recruitment and enrollment strategies will also need to be considered such as adaptive enrichment design or biomarker and treatment interaction designs (i.e. inclusion of both biomarker-positive and biomarker-negative patients) which can help researchers understand the treatment effect within subgroups to demonstrate significance of response in the biomarker-positive population.
Genomic Assays and Technology for Increased Trial Efficiency
With the additional genetic testing typically required for precision oncology trials, the recruitment may be slower. An important component of trial efficiency is the assay selected to test and establish an individual’s eligibility to participate in a trial. Genomic testing using tumor biopsies is a common way of confirming if a patient meets necessary genomic inclusion criteria for enrollment but is not always the most efficient. Facilitating programs that can assay an individual’s genome as quickly and efficiently as possible can decrease the amount of time taken to determine patient eligibility. For example, liquid biopsy assays (e.g. blood-based non-invasive genomic profiling technology) can benefit patients that may be too ill or are otherwise unable to provide an additional tumor specimen for genomic or other types of biomarker testing. The incorporation of faster and non-invasive genetic testing and validated technologies in precision trials allows for a greater volume of patient eligibility, as well as enhanced assessment of tumor heterogeneity.
Researchers have a greater appreciation of the heterogeneity of cancers and how a one-size-fits-all drug is no longer the most effective form of treatment. Precision medicine can significantly increase the efficiency of drug development by enabling more personalized, data-rich trials. As patients are increasingly involved in their health, patient-centric trial designs are gaining traction at pharmaceutical companies. With more efficient diagnostic tests being developed and training in data sciences increasing for researchers and healthcare professionals, precision medicine trials are creating a powerful approach to drug development and treatment.
For a more insights on developing a genomics strategy for successful drug development in oncology, visit https://clinicaldevelopment.parexel.com/latest-content/early-genomics-strategy-article.