FDA, industry discuss need for flexibility in early phase clinical development of cell therapy products

More flexibility in early-phase development for cell therapies is needed, a panel of US Food and Drug Administration (FDA) representatives and industry members said at a public meeting hosted by Friends of Cancer Research and the Parker Institute for Cancer Immunotherapy.

Vijay Kumar, acting director of the Office of Therapeutic Products (OTP) in the FDA Center for Biologics Evaluation and Research (CBER), said the agency is considering the feedback it received from its joint workshop with industry on considerations for pediatric cell and gene therapy (CGT) clinical trials (RELATED: Expert: FDA, industry still wary of enrolling patients in early cell and gene therapy trials, Regulatory Focus 9 April 2026).

Kumar told attendees that FDA is “moving towards a more disease-context sensitive, mechanism-aware framework for pediatric eligibility, one that does not solely rely on temporal sequencing of the studies from the adults.”

FDA will consider whether early inclusion in trials is “scientifically and ethically justified based on our current understanding of the disease, characterization of the product, and the mechanism of therapy,” Kumar said.

Another big change following the meeting is that FDA’s current thoughts on pediatric enrollment for these trials are that it “should be addressed as a central design question, not as an afterthought to be resolved in the post-approval setting,” he added.

Considerations for pediatric early phase trials

FDA offers more flexibility in early-stage studies, including phase-based current good manufacturing practice (CGMP) requirements, adaptive dose escalation, smaller sample size, and exploration of biomarkers and novel endpoints, Kumar noted. The agency encourages sponsors to explore patient selection and enrichment strategies in early-phase clinical trials.

“The primary goal in the early-phase studies is establishment of safety and dose response definition, and not necessarily drawing inferences on efficacy,” he said.

To provide flexibility in later-phase studies, Kumar pointed to the recent FDA shift allowing single, adequate, well-controlled studies with confirmatory evidence (RELATED: FDA to tighten approval requirements for CAR T-cell therapies, Regulatory Focus 9 December 2025).

“I must stress that at the FDA, we are focused on the quality and the persuasiveness of the clinical data, not merely on the quantity of the studies,” he said. “We continue to be flexible and balancing pre- and post-approval data requirements. We are open to extrapolation of indication to the pediatric population based on the understanding of the disease, characterization of the product, and the applicable clinical data.”

Kumar also addressed the trend of some companies conducting early-phase studies overseas due to lower costs and potentially faster enrollment of a more diverse trial population. He said FDA has “a host of concerns” regarding product quality and interpretability of scientific data on safety and efficacy for these trials. These concerns include, but are not limited to, adherence to risk-based CGMP, integrity of the manufacturing chain, and the ability to inspect facilities.

Other FDA concerns about early-phase trials outside the US include data integrity, study oversight for safety, the nature of the informed consent process, commitment to long-term follow-up, and the applicability of non-US requirements for sponsors seeking product approval in the US.

Unless companies are engaged with consultants and contact research organizations familiar with FDA’s current modernization efforts, “sponsors may do studies outside the US, there may be a short-term benefit, but in the long run, it might prove counterproductive to them,” Kumar said.

DLT framework

Travis Quigley, chief development officer at Kelonia Therapeutics, said that his company, one challenge with investigational new drug (IND) readiness was consistency and flexibility. He said that dose-limiting toxicity (DLT) criteria for CGT, such as CAR-T, may be an area for alignment because it has “sentinel dosing strategy and study pausing rules that are consistently applied across the board.”

“You have confidence going into an IND that those types of things and study design aren't going to change,” Quigley said.

Kumar said at FDA, staff encounter firms with different approaches to measuring DLT in their products, and efforts to harmonize those approaches could be difficult. “There is a diversity of indications, there’s a diversity of sponsors, and our reviewers find the DLT very, very challenging,” he said.

Rosanna Ricafort, senior vice president, head of cell therapy, medical, at Bristol Myers Squibb, said that her company has “amassed an extensive amount of clinical data through our portfolio in myeloma, lymphoma, autoimmune disease, and there’s a tremendous amount of clinical and regulatory precedent that we learn from executing those trials.”

She noted the company has built its own internal common framework for early development studies, but that advantage isn’t likely available to smaller firms.

“What I think would be helpful if we’re going towards a solution-oriented path is having an intentional common framework that has structural starting points on those essential protocol elements that are common throughout all of early-phase development in cell therapies,” Ricafort said.

This could include elements like DLT criteria, safety monitoring, inpatient monitoring, and dose escalation. “I think that would go a long way for elevating that,” she said.

“If we had an intentionally designed common framework, that would be beneficial and really improve efficiencies in the pre-IND, IND space,” she added.

Despite significant variability in the types of cell therapies being developed and the proposals FDA is reviewing, sponsors would benefit from a “common starting point where deviations are really rare and very specific to a very specific issue—whether it’s lack of data or [a] novel therapy where we expect the clinical study to be sensitive enough to detect it,” said Lola Fashoyin-Aje, a clinical regulatory strategy consultant and session moderator.

FDA signaled it was open to conversations and potential collaborations with industry and other stakeholders on how to develop a common framework for early-phase CGT trials.

“If we can standardize more of those features, that would be better for everybody, from the patients, from the sponsors to the regulators—everybody,” Kumar said.

FOCR