Biomarkers for Basket & Umbrella Trial Designs

How identifying specific biomarkers makes them more effective

M2GEN Identifies Critical Cancer Biomarkers to Enhance the Effectiveness of Basket & Umbrella Trial Designs

The oncology landscape is shifting, and there are several promising developments on the horizon. As a result of groundbreaking advances achieved in the field of genomics in recent years, cancer care is becoming more personalized—and thus more effective—with the development of therapies that can target a tumor’s unique genetic characteristics. Specifically, the identification of biomarkers is allowing scientists to better understand the genetic drivers of cancer so they can anticipate how tumors will behave. As such, by better understanding the present, they can more accurately predict the future.

As the biopharmaceutical industry focuses more fully on developing and delivering targeted cancer therapies, biomarker-guided clinical trials are increasingly needed to evaluate those therapies. However, to ensure the success of those important and complex studies, oncology researchers first need to find new strategies to design them and gain access to a sufficient pool of eligible patients to support them.

The Challenges of Clinical Research in Precision Medicine

Traditionally, the oncology drug development process has involved the study of a single drug in a single cancer population in a single clinical trial. In contrast, today’s master protocols provide an overarching structure that allows researchers to study multiple drugs and cancer populations simultaneously in one trial, leading to a more efficient and accelerated drug development timeline.

One type of master protocol is a basket trial, which can be designed to incorporate multiple substudies of a single drug or drug combinations across several cancer populations (“baskets”) as defined by cancer stage, histology, prior therapies, genetic biomarkers, and/or demographics. For example, a basket trial could include patients who are known to have a specific genetic mutation in common, regardless of the site of origin of their tumor.

Another type of master protocol is an umbrella trial, which can be designed to incorporate multiple substudies of drugs administered alone or in combination in a single cancer population. As such, one type of cancer could serve as the “umbrella,” and underneath it, various substudies could be conducted to evaluate the effectiveness of different therapies against tumors with different biomarkers.

Due to their ability to address multiple interrelated questions in one trial, master protocols have emerged as the leading way to conduct clinical research in precision medicine. For example, because master protocols incorporate multiple substudies, the efficacy of an investigational drug can be determined faster and more efficiently requiring fewer patients overall in a single basket trial as compared to conducting several traditional trials to address the same questions. As such, master protocols not only hasten the drug development cycle but also lead to R&D cost savings for biopharmaceutical companies as they perform the vital work needed to bring new lifesaving cancer therapies to market.

Despite the promise of master protocols, however, some difficult challenges remain. Most notably, their statistical strong suits—aggregation and borrowing power—necessitate a highly complex trial design. Basket and umbrella trials incorporate multiple substudies, each of which must be designed with a specific objective in mind. What’s more, while patient recruitment is a key determinant of the success of any clinical trial, biomarker prevalence directly affects the size of the pool of suitable candidates for biomarker-driven studies. To identify eligible patients, researchers must gain access to—and thoroughly analyze—massive amounts of clinical, molecular, and tumor specimen data.

M2GEN Is Addressing Those Challenges Head-On

An oncology-focused bioinformatics company, M2GEN understands the myriad of challenges faced by today’s oncology researchers as they strive to make cancer therapies more personalized. For instance, the process of identifying patients with specific predictive biomarkers for clinical trials has been historically time- and resource-intensive. M2GEN is working to change that. We are committed to helping our research partners accelerate their drug development programs, make better-informed decisions, and improve their efforts to create targeted therapies for cancer patients.

The sources of information and data management solutions that support oncology drug development have evolved considerably over the last several decades, opening the door for landmark discoveries that can alter the course of cancer care for current and future patients. Consider M2GEN’s patented Total Cancer Care® (TCC) research protocol. As members of the Oncology Research Information Exchange Network® (ORIEN), many of the nation’s leading cancer centers contribute to TCC, the bedrock of a proprietary bioinformatics platform that has grown to become a powerful weapon in the fight against cancer. Specifically, TCC incorporates de-identified clinical and molecular data from a diverse population of hundreds of thousands of patients who consent to be followed for life and donate tissue samples that were not used for clinical purposes so they can be used for molecular analysis and research.

One of the most robust cancer-focused data resources available in the world today, TCC supports a clinical trial matching program that can both improve the design of biomarker-driven trials and significantly reduce the timeline for identifying suitable patients for enrollment. By utilizing longitudinal clinical, molecular, and specimen data to stratify patients based on specific oncology biomarkers, researchers are better positioned to match the right patients to the right clinical trials and thereby minimize the risk of recruitment failure.

Precision Medicine Is Improving Cancer Outcomes

Tumors are infinitely diverse. As such, it is impossible for oncology researchers to gain a “one-size-fits-all” understanding of cancer and approach to treatment. But through the practice of precision medicine, the focus shifts away from the average cancer population and toward the individual cancer patient, directly leading to better outcomes and quality of life.

At M2GEN, we anticipate that the future of cancer care will be profoundly dependent on the use of oncology biomarkers to inform clinical decisions and will guide physicians at every step of disease management. We also believe the future starts now. Contact us for information about our custom and ready-made data solutions that leverage the power of bioinformatics.