The US Food and Drug Administration (FDA) released a draft guidance for industry that provided advice on designing and conducting adaptive clinical trials that would allow companies and researchers to assess different aspects of a drug in development in a single clinical trial — all while enrolling the minimum number of study participants necessary to obtain this information.
The guidance, entitled “Expansion Cohorts: Use in First-In-Human Clinical Trials to Expedite Development of Oncology Drugs and Biologics,” is open for comment until October 12, 2018.
“As part of our ongoing efforts to advance more efficient ways to develop medical products, the FDA is encouraging pioneering new ways that innovators can modernize the way they conduct clinical trials,” FDA Commissioner Scott Gottlieb, MD, said in a prepared statement.2 “The approach we’re describing in new guidance today is to help innovators to evaluate drugs in trials that are potentially lower cost, more efficient, and could enable us to learn more about the safety and efficacy when compared to traditional trial designs.”
First-in-human expansion cohort trials have a “single protocol with an initial dose-escalation phase that also contains three or more additional patient cohorts with cohort-specific objectives,” according to the draft document.1 Among the possible objectives for the additional cohorts are assessment of antitumor activity, assessment of a reasonably safe dose in specific populations, evaluation of alternative doses or schedules, establishment of dose and schedule for the investigational drug administered with other oncology drugs, or evaluation of the predictive value of a potential biomarker.
According to the FDA, the guidance provides recommendations in 4 areas. First, it lists characteristics of drug products best suited for consideration for development under a multiple expansion cohort trial. For example, a drug formulation with drug substances that have attributes that would allow for straightforward bridging between early drug product formulations and marketing formulations may be the type of investigational therapy that would be the most appropriate for multiple expansion cohort trials.
The guidance also contains information about what to include in an investigational drug application submission to support the use of individual cohorts. Next, the guidance lists when to interact with the FDA on planning and conducting multiple expansion cohort studies. Finally, the guidance suggests how to construct safeguards for patients enrolled in first-in-human cohort studies and how to protect them from potentially synergistic drug toxicities.