On Monday, May 22, Friends of Cancer Research (Friends) hosted a hybrid public meeting titled “The Next Generation of Cellular Therapies: A Blueprint to Accelerate Development.” This meeting built on Friends’ previous work on Cell & Gene Therapies and was the second of two meetings in 2023 to explore next steps in the field. This meeting’s white paper and panel discussions will help facilitate the development of the next generation of cellular therapies and support policy discussions between key stakeholders in the drug development process.
The meeting began with a discussion between Steven Rosenberg, Chief of Surgery at the National Cancer Institute (NCI), and Arie Belldegrun, Executive Chairman and Co-Founder of Allogene Therapeutics. The two discussed early collaborations and research that led to the development of the successful CAR T cell therapies we have today. They also discussed future opportunities such as new treatment modalities, expanding the use of cell therapies for the treatment of solid tumors, and moving toward “off-the-shelf” cell therapies.
“The critical observation is taking a T-cell receptor and moving them into a patients normal cells.” – Steven Rosenberg, NCI
Session 1: A Risk-Based Data Extrapolation Plan for Developing Next Generation Cell Therapies was moderated by Patrick Hanley, Children’s National Hospital, with panelists Marc Better, Pharmefex, Christine Brown, City of Hope, Vicki Coutinho, Independent, Michael Kalos, Next Pillar Consulting, and Ingrid Markovic, U.S. Food and Drug Administration (FDA). First, panelists described how prior and current cell therapy development experiences have helped to identify effective approaches for developing the next generation of cell therapies. Panelists provided several examples of modifications and improvements to enhance existing cell therapies such as introducing switches into cells, engineering cells beyond T cells and K cells (e.g., gamma delta cells, macrophage, etc.), and redesigning cell therapies to remove the need for chemotherapy preconditioning. Panelist Ingrid Markovic then described regulatory opportunities for leveraging data and evidence from other product versions to help expedite development and review such as leveraging prior data to set preliminary acceptance criteria for a next-generation product. She also noted FDA is working on a guidance document to inform use of platform technologies for cell therapy manufacturing. She described how platform technologies can allow developers to leverage information to support multiple product applications. Panelists also described best practices for generating data that can support data extrapolation to future product versions. The panelists noted that building robust product knowledge through characterization studies and understanding sources of variability are critical to support leveraging data across products and ensure consistency across product lots.
“We need to build out object quality. The data has to be quantitatively sound and understood.” – Michael Kalos, Next Pillar Consulting
Session 2: Emerging Considerations for Next Generation Cell Therapies was moderated by Jonathan Jazayeri, Kite, A Gilead Company, with panelists Nigel Yateman, Novartis, Larissa Lapteva, U.S. FDA, Jae Park, Memorial Sloan Kettering Cancer Center, Raj Puri, Iovance Biotherapeutics, and Jennifer Yohrling, Janssen R&D. First, Raj Puri, and Nigel Yateman provided examples of how experience with first generation products has informed continued efforts to enhance cell therapies. Next, Larissa Lapteva described the FDA’s perspective of how the umbrella design approach, described in the FDA’s November 2022 guidance on “Studying Multiple Versions of a Cellular or Gene Therapy Product in an Early-Phase Clinical Trial,” can support more efficient development of cell therapies by providing preliminary clinical data early in development to help inform optimal design. Jae Park described how, from a clinician’s perspective, the single-IND approach outlined in FDA’s guidance provides both cost and time savings by avoiding submissions of duplicative information for multiple products. Panelists also discussed trial design considerations for next-generation therapies and considerations for extrapolating data for the treatment of a different type of cancer or in a different line of therapy. Finally, panelists discussed opportunities to facilitate interactions with the FDA on cell therapy development and how to overcome challenges to expanding patient access to cell therapies.
“You don’t know which technology is going to work. It may not be a one size fits all solution.” – Jonathan Jazayeri, Kite, A Gilead Company
Session 3, The Next Horizon for Cancer Therapies, was moderated by Margaret Anderson from Deloitte Consulting with panelists Peter Marks, U.S. FDA, Arie Belldegrun, Allogene Therapeutics, Marc Hurlbert, Melanoma Research Alliance, and Tal Zaks, OrbiMed. The discussion began with panelists sharing their perspectives on what a regulatory “blueprint” for cell therapy development would look like. Tal Zaks noted the current focus should be on key factors in the process of developing cell therapies. Next, panelists discussed challenges facing the cell therapy field, noting that science is advancing at a rapid pace. Peter Marks discussed how artificial intelligence (AI) and machine learning (ML) have the potential to enable more efficient manufacturing processes for cell therapies. He also noted that AI can be used to analyze adverse event reports to improve evaluations of safety and effectiveness. Arie Belldegrun noted the important role the FDA will play in helping address current challenges by leveraging learnings from a wide array of development programs and communicating them to support best practices and advancements. The panelists then discussed how to improve clinical trial designs, as well as how to enhance cooperation between the FDA and industry.
“The goal is not to make a PowerPoint presentation; the goal is to get drugs to patients.” – Tal Zaks, OrbiMed