On November 14, 2023, Friends of Cancer Research (Friends) hosted our 16th Annual Meeting in Washington, D.C. Discussions at the meeting were the culmination of three working groups led by Friends over the past year, which collaboratively proposed solutions for three key challenges in oncology drug development: dose-finding in early phase trials, incorporating pragmatic elements in clinical trials, and using data from academic-led studies for regulatory decision-making.
The meeting began with a keynote conversation between Rob Califf, Commissioner, U.S. Food and Drug Administration (FDA), and Monica Bertagnolli, Director, National Institutes of Health (NIH), moderated by Jeff Allen, President & CEO, Friends. The two discussed opportunities to improve the conduct of clinical trials. They noted the need to build infrastructure that supports the use of clinical practice data for research, and highlighted how quality assessment, observational analysis, and global evidence generation could benefit the clinical trial ecosystem. They also highlighted the challenges of post-market evaluation, particularly in determining comparability of treatments, how to combine treatments, and the appropriate duration of treatment. The two also considered how the NIH and the FDA could collaborate more strongly to advance clinical trials. Finally, the speakers emphasized the importance of evidence-based medicine and encouraging clinicians to collaborate with researchers to promote the use of data and technology to improve patient outcomes.
Panel 1 – Early Phase Trials: Data Implementation and Interpretation for Dose Finding
Julie Bullock of Certara moderated the first panel discussion with panelists Judith Fitzgerald a Patient Advocate, Ramon Kemp of GSK, Enrique Sanz Garcia of Princess Margaret Cancer Centre, Mirat Shah of the U.S. FDA, and Gita Thanarajasingam of Mayo Clinic.
To begin the panel discussion, Mirat Shah explained the goals of the FDA Oncology Center of Excellence (OCE) Project Optimus. The panel highlighted the critical role patients play in advocating for patient-centered approaches to dose optimization. Panelists also discussed work to establish standardized methods for measuring, analyzing, and incorporating patient reported outcomes (PROs) in early clinical trials. Collecting and sharing PRO data in real-time with physicians may be a more effective approach to incorporating patient information into clinical decision-making. Participants noted PROs can provide valuable data to assess tolerability, including data to characterize chronic symptomatic low-grade toxicities.
Panelists noted the various phases of dose evaluation throughout drug development, and unique considerations for what dosing data to collect and assess at each phase. Emerging technologies, such as artificial intelligence/machine learning (AI/ML) and circulating tumor DNA (ctDNA), may be leveraged to improve the patient experience and efficiency of assessing doses in clinical trials.
Finally, panelists discussed the importance of including diverse patient populations in clinical trials. Panelists noted there can be challenges to conducting additional dose optimization studies in the postmarket setting so, ideally, representative dose optimization studies should occur prior to approval.
Panel 2 – Incorporating Pragmatic Trial Elements into Oncology Drug Development
The second panel was moderated by Nafsika Kronidou Horst of F. Hoffmann-La Roche with panelists Erin Larkins of the U.S. FDA, Boris Kin Lin of Eli Lilly and Company, Sumithra Mandrekar of Mayo Clinic/The Alliance for Clinical Trials in Oncology, Kristin McJunkins a Patient Advocate, and Margaret Mooney of NCI Cancer Therapy Evaluation Program.
Erin Larkins shared insights into the genesis of the FDA OCE’s Project Pragmatica, which stemmed from promising results of a randomized phase II lung cancer trial that lacked sufficient data for regulatory approval. This led to the initiation of the Pragmatica Lung Trial to answer unresolved efficacy questions with streamlined data collection and an overall more pragmatic approach.
Panelists discussed how various pragmatic elements such as simplification of trial processes, expanded eligibility criteria, and streamlined data collection could help to address the inherent challenges of clinical trials. The speakers articulated the importance of harmonizing research with clinical care, integrating electronic health records (EHRs), and fostering international collaboration to augment the quality and generalizability of trial outcomes. Ethical considerations surrounding data collection practices were underscored, with panelists emphasizing the need for consensus among regulatory groups.
The panel also noted early engagement with regulatory agencies, the role of leadership, the need for culture shifts, and the integration of technology to streamline clinical trial processes. Overall, the panel underscored the potential advantages of incorporating pragmatic elements into trials, aligning research objectives with real-world outcomes, and steering the clinical trial methodologies towards greater efficiency and inclusivity for patients.
Lunch Keynote – Overview of OCE Projects
FDA OCE Director Richard Pazdur led the lunch keynote conversation with FDA OCE leadership who focused on several of the FDA OCE’s ongoing initiatives:
- Rea Blakey introduced “Project Community” which supports engagement with underserved communities to increase awareness around cancer risk.
- Mitchell Chan introduced “Project Facilitate,” which facilitates expanded access to oncology drugs by providing personalized support to physicians, regulatory professionals, and healthcare providers.
- Angelo de Claro discussed “Project ORBIS,” a collaboration with international regulators that helps facilitate review and international approval of cancer drugs.
- Gautam Mehta introduced “Project Confirm” which improves transparency around the outcomes from confirmatory trials for oncology accelerated approvals.
- Jeff Summers provided details on “Project Catalyst,” which assists small companies and academic researchers in developing new oncology therapies.
The conversation focused on how each of these initiatives helps to improve regulatory processes and development of oncology drugs, such as through ensuring timely confirmation of benefit for accelerated approvals, significantly reducing review times for expanded access applications, and fostering global collaboration to get novel therapies available to patients around the world.
Panel 3 Discussion – Maximizing Use of Data from Academic-Led Studies for Regulatory Decision-Making
Panel 3 was moderated by Kathleen Winson of Genentech, with panelists Kristina Laumann of Mayo Clinic, Margaret Mooney of NCI Cancer Therapy Evaluation Program, Christy Osgood of the U.S. FDA, Russ Palmer of EMD Serono, and Sunita Zalani of Merck & Co., Inc.
The panelists discussed how current approaches to leveraging data from academic-led studies need to be improved to avoid delaying drug approval processes. The panelists underscored the value of a collaborative and collective effort involving academia, industry, and regulatory bodies. The discussion noted there are benefits of academic drug development, acknowledging its role in accelerating drug development, expanding scientific knowledge, and fostering collaboration with key opinion leaders. Panelists also acknowledged the challenges unique to academic clinical trials, such as differing data collection standards and intentions compared to regulatory submissions.
Proactive engagement with health authorities was highlighted as crucial to preventing delays in data submission for regulatory review. Strategies discussed included the establishment of a regulatory track for academic studies, a professional-grade data management system, routine engagement with industry sponsors, and ensuring early commitment and support from organizations like NCI and FDA. Panelists identified a few next steps to continue their work including ongoing discussions to support stakeholder engagement, decision-making on individual company processes, and adapting academic-led systems to meet FDA requirements. The panel also stressed the benefits of collaboration and resource-sharing between academia and industry in cancer research, urging industry partners to explore collaborations beyond trial periods.