Whenever I’m asked about what drives my passion for cancer treatment and oncology R&D, my answer is simple: with every innovation, we’re closer to extending life for patients who are out of time. By getting clinical trial design right, we have the potential to give people with cancer the best possible chance at one more day – for a graduation, a birthday, or an afternoon at home with loved ones.
Increasing the likelihood of success in oncology takes more than passion. It takes smart deployment of resources. Those outside the field don’t often realize how many critical capabilities, people and functions it takes to write a purposeful clinical trial protocol that has the potential to bring a successful cancer treatment across the finish line for patients. To make this happen, every person within the organization – from data managers, statisticians, to programmers, regulatory experts, trial managers, clinical and pharmacovigilance representatives who evaluate safety and ensure patients are being treated and managed accordingly to the protocol. Each brings vital insights and experience to the process.
At the outset of the study design process, the aim is to build and conduct broad trials that allow for the potential to explore and potentially impact a variety of cancers. These basket-type trials drive a purposeful approach to oncology R&D and become the first step in seeing how and where a molecule may have impact and inform direction of subsequent trials into specific tumor types, and line of therapy including meaningful dosing.
These early trials also provide essential insights into the safety aspects of the molecule, to help guide future decisions regarding dose selection and administration. Once results begin to appear, the approach becomes more focused on cancers that are most responsive to the investigational trial drug. This level of exploration goes deeper to pinpoint the right tumor type, at the right dose, for the right types of patients, as we work towards our goal of developing a drug with acceptable benefits and side effects.
Designing a Purposeful Trial Program
Different considerations can inform trial development process over time. For example, at Alkermes, we have re-designed an existing molecule (IL-2) with the goal of harnessing its benefits while mitigating toxicity issues, so our early trials were designed to get initial validation of that re-design. Before we could pursue anything more specific, we first needed to understand questions around the right dose, the populations we may see a signal in, how to manage patients effectively, and the impact of pharmacodynamic effects in the patients in our studies. These early-stage studies help researchers determine whether a molecule worked as expected based on the design hypothesis.
The hope with a purposeful approach is that asking the right questions and following the data will eventually help identify the specific populations or tumor types where a molecule may deliver the greatest amount of benefit, informing later-stage trial design. The real joy in development is ultimately finding and getting approval for a treatment for patients who will receive the maximum amount of benefit, addressing key unmet needs in the field. For example: defining dedicated cohort types in later-stage trials, and then narrowing in to explore specific tumor types and patients in different stages of treatment.
What makes our program at Alkermes unique is that we’ve been able to show with our early design elements that our molecule mechanistically meets our design objectives. Therefore, we’re now able to explore its effects in patient populations where there is a high unmet need; for example, in CPI-resistant tumors where existing drugs have limited activity or there are no alternative treatments (such as in mucosal melanoma) or where checkpoint inhibitors have not shown effectiveness (such as in platinum-resistant ovarian cancer).
After meeting design objectives, further exploration can occur including the potential to combine a therapy with other drugs that may offer new combination treatment options in specific disease areas. At Alkermes, this is what we’re most proud of with our program’s design: we’ve been able to design a novel-novel combination trial where we will evaluate whether our drug is an improvement over standard of care (SOC), and investigate the contribution of our drug and the combination therapy in benefitting patients over SOC. By carefully selecting a drug’s potential combination partner and strategically designing the combination trial, there is potential to bring two therapies to market in combination that may benefit a population where there is a high unmet need to find new treatment options.
Purposeful R&D takes teamwork to Improve Potential
Purposeful R&D takes teamwork, a concerted effort, and many bright minds to execute each aspect along the way. You feel it when it’s flat: with even one broken piece, it means there is less likelihood of success. But when you get it right and you bring innovation to patients, it’s a like beautiful orchestra that brings music to everyone’s ears.
Jessicca Rege serves as Vice President, Clinical Research Oncology at Alkermes, where she is responsible for establishing the company’s immuno-oncology development strategy and overseeing the execution of its global clinical trials. Dr. Rege joined Alkermes in 2020, bringing with her more than 15 years of experience in research, clinical development and global medical affairs. She previously held roles of increasing responsibility at Bristol-Myers Squibb, Eisai, Daichi Sankyo and Boehringer Ingelheim. Dr. Rege earned a Bachelor of Science from Carson-Newman, and holds both a Master of Science in Physiology and a Ph.D. in Pharmaceutical Sciences from Virginia Commonwealth University. She completed her postdoctoral fellowship in pediatric leukemia at the University of Pennsylvania’s Children’s Hospital of Philadelphia