A new draft guidance issued by the U.S. Food and Drug Administration (FDA) provides advice to sponsors regarding the design and conduct of first-in-human (FIH) clinical trials for cancer drugs and biologics. The draft guidance, issued in August 2018, describes the use of multiple expansion cohort trial designs as a means to expedite clinical development.
Specifically, the guidance provides FDA’s current thinking regarding:
- Characteristics of drug products best suited for consideration for development under a multiple expansion trial
- Information to include in investigational new drug application (IND) submissions to support the use of individual cohorts
- When to interact with FDA on planning and conduct of multiple expansion cohort studies
- Safeguards to protect patients enrolled in FIH expansion cohort studies.¹
First-in-human multiple expansion cohort trials: Opportunities and challenges
In the draft guidance, FDA defines FIH multiple expansion cohort trials as those with a single protocol in which an initial dose-escalation phase that also contain three or more additional patient cohorts with cohort-specific objectives. FDA outlines some of inherent challenges and risks of these studies, including:
- “Challenges in disseminating new safety information to investigators, IRBs, and regulators in a timely manner…
- Exposing a large number of patients across multiple, simultaneously accruing, cohorts to potentially suboptimal or toxic doses of an investigational drug
- Exposing more patients than required to achieve the cohort’s objectives.
- Inefficient drug development based on possibly missed interpretation of preliminary trial results and unplanned analyses that can lead to delays in proper clinical development.”1
Given these increased risks, FDA recommends that clinical trials with FIH multiple expansion cohorts be limited to investigational drugs for indications and patient populations in which the potential benefits justify the risks. Furthermore, FDA suggests that the patient population should be limited to patients with serious diseases for which no curative therapies are available,¹ The guidance also lists considerations based on cohort objectives (e.g. confirming safety of recommended Phase 2 dose, biomarker development, evaluation specific PK and pharmacodynamic aspects, etc.)
Pearl IRB is part of Pearl Pathways, a comprehensive life science product development services company. Pearl Pathways’ team possesses significant experience navigating regulatory challenges and clinical trials for drugs and biologics targeting cancer. Contact us today to discuss to discuss how our team can help get your product to patients quicker.