Adapting clinical trial designs to advance cancer research

What is the traditional model for clinical trials, and why is there a need for more innovative approaches?

Jason Luke (JL): In a standard cancer clinical trial, we typically recruit a set amount of patients to test how a single treatment (e.g., a new drug) or combination performs versus a standard treatment. Although this model has allowed us to test thousands of therapies in cancer research, it poses a couple of issues.

What do researchers need in order to design these types of trials?

Tim Reilly (TR): Before we even begin to conceptualize a novel trial, we focus on translational research to guide a hypothesis based on our understanding of tumor and immune biology. For instance, we’ve done a significant amount of research on the tumor microenvironment to understand various immune pathways and tumor evasion mechanisms, and how these pathways differ within groups of patients, or even individual patients over time. We also try to identify indicators of response to help establish which groups of patients are more likely to benefit, or are not likely to benefit, from investigational combinations.  Together, these learnings often serve as the foundation for innovative clinical designs.

Can you share an example of a new or innovative clinical trial design? 

JL: A really great example is a Bristol Myers Squibb-sponsored study that I’m leading called ADVISE (ADaptiVe Biomarker Trial that InformS Evolution of Therapy), which evaluates real-time, biomarker-driven patient selection for a range of I-O-based combinations. The interesting thing about ADVISE is that the study is designed in a way that allows us to perform prospective analyses on pre-treatment samples to assess the presence of certain biomarkers. From there, we can tailor each patient’s treatment combination based on their unique biomarker profile, allowing us to more closely mirror how patients are treated in the clinical setting. 

Learn More about the ADVISE Trial Design

TR: In addition to ADVISE, Bristol Myers Squibb is also sponsoring other platform type trials, including the platform known as FRACTION (Fast Real-time Assessment of Combination Therapies in Immuno-Oncology). The two trial concepts are very similar in the sense that multiple combinations are evaluated in a single study. But in the case of FRACTION, we are asking clinical questions around various combinations while analyzing biomarker data retrospectively to help us better understand the biological bases for responses – or lack thereof – to an investigational treatment combination. In addition, if a patient progresses, we can enroll them into another regimen within the trial. We can also add new combinations to the study on a rolling basis and pursue promising areas of science as they arise. Overall, this adaptive design gives us the flexibility to quickly assess and compare various treatment options in different stages of disease, which increases the opportunities for learning in a single study.

How do you see trial designs evolving in the future? 

TR: I think clinical trials will evolve in the same way pharmaceutical research and cancer treatment has over the past 30 years. Instead of a ‘one-size-fits-all’ approach, we’ll have ‘precision trial designs,’ meaning there will be a multitude of different trials using specific mechanisms and combinations of mechanisms in pre-defined patient segments that are tailored to specific hypotheses around those patients’ needs. This doesn’t mean that the traditional method will become obsolete, but I do think we’ll begin to rely on more innovative designs and apply the insights from focused clinical questions more broadly to larger groups of patients. 

Learn more about how FRACTION is simplifying the clinical trial process.