Over the past 20 years, the investment in research and development of cancer therapies has been unprecedented, and the pace of new drug development has been accelerating. To illustrate this trajectory, the U.S. Food and Drug Administration (FDA) approved 71 treatments for solid cancers in adults between 2002 to 2014, but from 2017 to 2022, there were 161 new approvals. This rapidly expanding armamentarium of cancer therapeutics, often developed using novel trial designs, endpoints, and associated biomarkers, has resulted in a significant expansion in treatment and regulatory complexity, highlighting a need for investigators and sponsors to have a deep understanding of the requirements and regulatory processes of global regulatory authorities.
About the AAADV Workshop
Since 2004, the Accelerating Anticancer Agent Development and Validation (AAADV) Workshop has been a forum in which clinical and translational investigators developing anticancer agents can interact with experts in trial design, trial execution, and regulatory science to examine the safety and efficacy of these agents, as well as with patients who participate in their clinical development and evaluation. Specifically at the workshop, experts in cancer drug development and patient advocates discuss best practices with representatives of regulatory agencies, such as the FDA and other national and international agencies, regarding the development and validation of new anticancer and cancer prevention agents, as well as diagnostic, prognostic, and predictive devices. The workshop is conducted in an interactive atmosphere, with an emphasis on the design and analysis of highly innovative development strategies in the era of precision medicine and immunomodulators—from nonclinical platforms to first-in-human clinical trials, to biomarker validation, to enabling trials, to pivotal efficacy trials.
The original concept for this workshop emanated from the hope that best practices would always be employed when designing clinical studies in which participation of patients with life-threatening diseases was necessary. Leaders from clinical research organizations, the pharmaceutical industry, and, critically, from the FDA prioritized the role of patients and their voluntary participation in clinical research as the key driver to stimulate open discussions of best clinical research practices to determine the safety and efficacy of new agents. Generating reliable clinical data from each clinical trial participant was seen as a major goal and a key incentive in the creation of this forum.
Duke University, the U.S. National Cancer Institute (NCI), the FDA, the American Association for Cancer Research (AACR), ASCO, and Susan G. Komen jointly sponsored and organized many of the annual in-person AAADV Workshops held from 2004, with cumulative attendance exceeding thousands of participants. As with many in-person events, the COVID-19 pandemic interrupted these annual meetings. Nonetheless, the AAADV Workshop resumed in 2022 as a virtual meeting, with an emphasis on global cancer drug development, especially for participants developing therapies for rare cancers, pediatric cancers, and rare molecular subtypes of common cancers. AAADV workshops have evolved with an aim to refocus the workshop on global drug development and include participation by regulatory agencies not only the FDA, but also including the European Medicines Agency, the Japan Pharmaceutical and Medical Devices Agency, and the China National Medical Products Administration, among others. The 2022 and 2023 meeting agendas as well as archived videos of all presentations are available at www.AAADV.org and highlight this commitment to cancer drug development for the global oncology community.
Amended Organizational Model
In recent years, many educational programs have been developed by the Oncology Center of Excellence at the FDA in collaboration with AACR, ASCO, and Friends of Cancer Research, among others, to support training in regulatory science, which has created a robust environment for investigator training and professional development. In view of the greater number of educational programs in regulatory science now available, current and former leaders and program committee members of the AAADV met in a think-tank format to discuss strategic priorities and plans for the next decade of the AAADV Workshop that will complement this new regulatory science education ecosystem.
Based on these discussions, the AAADV Workshop amended its organizational model by creating a 501(c)3 organization (the AAADV Workshop Foundation) to facilitate obtaining unrestricted educational grants to support in-person meetings and virtual access to meeting materials by global participants. In addition, in-person and virtual educational activities in collaboration with the Triangle Center of Excellence in Regulatory Science and Innovation, sponsored by the FDA, will now be planned throughout the year.
2025 AAADV Workshop
At this time, the annual AAADV Workshop is returning to an in-person meeting, on May 14–15, 2025, to be held at the North Bethesda Marriott in Bethesda, Maryland. The program committee of Drs. Schilsky, Canetta, Fleming, and Lyerly are pleased that former FDA commissioner Dr. Robert Califf will be the keynote speaker, highlighting his experience and providing his perspective on the next era of drug development.
Four plenary sessions will follow, each consisting of a series of focused talks from experts in the field, followed by a moderated discussion emphasizing regulatory perspectives. The first plenary session will focus on the utility of large trials that use multiple experimental agents from different sponsors to identify signals of anticancer activity in an efficient manner. Specifically, the session aims to review and determine what has been learned from such trials and how to organize them even more efficiently in the future. Trials to be discussed include the Beat AML and PedAL studies (sponsored by the Leukemia and Lymphoma Society), the Lung-MAP study (organized by the NCI with support of the Foundation for the National Institutes of Health and Friends of Cancer Research), the NCI-MATCH study, and the ASCO TAPUR study.
The second session will focus on global drug development and highlight the experience in multinational clinical cancer research from one of the leading organizations, the European Organisation for Research and Treatment of Cancer. Additional topics will address inclusion of representative populations in international clinical trials, as well as the complexities of conducting clinical trials in which regional variations in medical practice and standards of care may exist. An additional plenary session on global cancer drug development will focus on Nigeria, which has a vision of becoming a clinical trial hub and innovation ecosystem.
The second day of the workshop will consist of two plenary sessions; the first will be on developing and implementing complex biomarkers to guide cancer treatment. This morning session will focus on the rapidly expanding role of artificial intelligence (AI) in cancer drug and biomarker development and on network analysis to identify novel biomarkers and targets. This will be followed by talks focused on the clinical applications of transcriptomics and AI-assisted digital pathology.
Finally, the workshop will conclude with a plenary session focusing on choosing proper primary endpoints and registrational oncology trials that focus on indolent cancers. This topic will allow a discussion of reliable assessment of efficacy and safety in trials of indolent cancers, when overall survival may take a long time to ascertain, as well evaluation of the effects of cancer treatments on how patients feel and function as a potential approval endpoint.
Long-Term Goals
Although it is understood that exciting therapeutic opportunities for cancers are being developed in research laboratories around the world, these new molecules often are accessible only to the elite research institutions that are in major cities. Most patients with cancer do not have access to these institutions and do not have access to these trials. Consequently, by creating a forum for best practices, and by providing educational content to early-career investigators, the AAADV Workshop aims to support researchers and clinicians in the broader medical community and provide the opportunity for clinicians and patients to access new therapeutics in their communities.
The AAADV has been instrumental not only in advancing the methodology of cancer clinical trials, but also in the training of a new generation of clinical investigators in both academia and industry. Consequently, a long-term goal is to expand the global educational and training infrastructure to continue to support and develop a clinical investigator workforce around the world that is expert in clinical trial design as well as trial conduct and analysis and has a deep understanding of regulatory requirements to advance new products to market.
Through these educational activities, including annual workshops and other ongoing educational activities, the AAADV Workshop hopes to catalyze efforts by senior investigators to provide training and education as well as to promote the adoption of policies that accelerate the development of new therapeutics for uncommon or rare conditions (especially those occurring in children). The AAADV Workshop also hopes to provide a foundation in regulatory science that will support the development and evaluation of products for these specific populations in a timely, reliable, and cost-efficient fashion, supporting the translation of the science to benefit patients.
DISCLOSURE: Dr. Lyerly is a co-founder and equity holder in Replicate Bioscience, TRIO Pharmaceuticals, and Sonokine Biosciences; is an equity holder in AlphaVax; serves as principal investigator or co-investigator and receives research grants in support from the U.S. Department of Defense and the National Institutes of Health, although they were not used in the production of this article. Dr. Canetta and Dr. Fleming reported no conflicts of interest. Dr. Schilsky is a board member and has equity in Leap Therapeutics and Clarified Precision Medicine; serves as a compensated consultant to Cellworks, Flatiron Health, Lind AI, and Zephyr AI and a compensated member of data and safety monitoring boards for trials sponsored by Toray Pharmaceuticals and Wugen; serves as principal investigator of the ASCO TAPUR study, and ASCO receives research grants in support of the study from AstraZeneca, Bayer, Boehringer Ingelheim, Bristol Myers Squibb, Genentech, Lilly, Merck, Pfizer, and Taiho Pharmaceutical; however, Dr. Schilsky does not receive personal remuneration from these companies.
Dr. Lyerly is Professor of Surgery, Duke University School of Medicine, and a member of the AAADV Workshop Foundation. Dr. Canetta is a member of the AAADV Workshop Foundation. Dr. Fleming is Professor, Biostatistics at the University of Washington, and a member of the AAADV Workshop Foundation. Dr. Schilsky is Professor Emeritus, University of Chicago, and a member of the AAADV Workshop Foundation.
