Friends of Cancer Research (Friends) held our 2024 Annual Meeting on November 12th in Washington, D.C. The meeting was a culmination of the collaborative efforts of scientists, clinicians, advocates, and policymakers to develop innovative solutions to challenges in oncology drug development. The meeting featured two keynote conversations with the U.S. Food and Drug Administration (FDA) Commissioner Robert Califf and Director of the National Cancer Institute (NCI) Kimryn Rathmell, and panels discussing three topics: interim OS evaluations, pragmatic trials in the post–marketing setting, and incorporating ctDNA in prospectively designed trials.
Morning Keynote Featuring Robert Califf, Commissioner, U.S. FDA
(Click here to watch the Keynote Conversation)
The meeting began with a forward-looking conversation between FDA Commissioner Robert Califf and moderator Ramsey Baghdadi of Prevision Policy. The two discussed the future of the FDA, including potential changes during the next administration and their impact on FDA and regulatory processes. Dr. Califf expressed confidence in the agency’s civil servants and scientists who work diligently to make evidence-based decisions. On the topic of drug pricing, Dr. Califf noted the importance of aligning pricing with demonstrated clinical benefit. Looking to his remaining time as FDA Commissioner, Dr. Califf highlighted the need for pragmatic trials to make healthcare more responsive and efficient. He expressed hope for greater efforts to address public health crises, particularly reform on tobacco and food, to counteract chronic health issues and improve life expectancy.
Session 1: Interim Overall Survival Evaluations and Implications for Trial Designs and Analysis Plans
Read the Session 1 White Paper here.
Geoff Oxnard of Eli Lilly and Company opened the first panel session with a presentation highlighting the complexities of interpreting interim overall survival (OS) data. Using trial examples, he illustrated how crossover, treatment sequencing, and other trial design elements can impact interim OS results and complicate interpretation alongside meaningful improvements in intermediate endpoints such as progression-free survival (PFS) and disease-free survival (DFS). Dr. Oxnard proposed several potential solutions, including use of quality of life (QoL) metrics to provide additional context for evaluating the risk-benefit balance of a regimen when interim OS data are inconclusive.
The presentation set the stage for the Session 1 panel moderated by Keith Flaherty of Mass General Cancer Center, with panelists Nicole Gormley, U.S. FDA, David Mitchell, Patient Advocate, Geoff Oxnard, Eli Lilly and Company, Lisa Rodriguez, U.S. FDA, and Antony Sabin, GSK. Dr. Gormley noted how advancements in therapies have led to significant improvements in OS for some cancer types, prompting a shift towards using intermediate endpoints for regulatory decision-making, with interim OS providing safety information. The panelists discussed key considerations when interpreting conflicting endpoint results, especially when outcomes like response rate or PFS suggest benefit and interim OS data suggests potential harm. Panelists proposed multiple strategies and methodologies for clinical trial design and interim OS data analyses, focusing on predictive modeling, treatment switching methodologies, tipping point analysis, and managing crossover in studies. The conversation also touched upon the need to address issues related to long-term follow-up and patient consent withdrawal. The panelists emphasized the importance of refining data collection methods, establishing best practices around study design and analysis of interim OS data, and providing greater clarity on expectations for the use of interim OS in assessing risk-benefit profiles.
Session 2: Enhancing Post-Marketing Studies with Pragmatism
Read the Session 2 White Paper here.
Paul Kluetz of the U.S. FDA began Session 2 with a presentation on how the incorporation of pragmatic elements into clinical studies can help minimize patient burden and improve the generalizability of clinical trial results. He emphasized the need for modernizing evidence generation through more efficient and patient-centric approaches, such as through post-market studies and leveraging real-world data (RWD) from electronic health records. Dr. Kluetz described the continuum of clinical trial designs, ranging from highly explanatory to more pragmatic approaches, and stressed the importance of revisiting eligibility criteria, decentralizing trial elements, and reducing assessments to streamline study protocols for real-world applicability.
Following the presentation, Richard Schilsky of the University of Chicago moderated a panel discussion with Allen Chen, AstraZeneca, Trixia Camacho, Bristol Myers Squibb, Eva May, Patient Advocate, Neal J. Meropol, Flatiron Health, Peter O’Dwyer, University of Pennsylvania, and Donna Rivera, U.S. FDA. The panel discussion focused on introducing pragmatic elements into post-market clinical trials, emphasizing the importance of tailoring trials to be fit-for-purpose based on the trial objectives and intended use of trial data. Panelists discussed the benefits and risks associated with pragmatic elements, highlighting how considerations will vary based on the study goals. Panelists highlighted how broadened eligibility criteria can enhance representation in clinical trials and how streamlined safety data collection can reduce operational burdens, making trials more accessible, particularly for community sites. Eva May underscored how pragmatic elements such as electronic informed consent and patient-reported outcomes (PRO) surveys help to make trials more patient-centered while providing important information on patient experiences and safety. Panelists also highlighted the importance of publicizing both successes and failures in pragmatic trials to collectively advance the field and drive progress in cancer research.
Session 3: A Common Strategy for Using ctDNA as an Intermediate Endpoint in Prospectively Designed Trials
Read the Session 3 White Paper here.
Hillary Andrews, Friends Director of Regulatory and Research Partnerships, presented new data from the Friends ctMoniTR project showcasing results from 4 randomized controlled trials (RCTs) (~1,000 patients) comparing anti-PD(L)1 (with or without chemotherapy) treatment to chemotherapy alone. Results demonstrated that ctDNA molecular response associated with improved OS for patients with advanced non-small cell lung cancer (aNSCLC) treated with anti-PD(L)1 and/ or chemotherapy, with a stronger magnitude of change observed in the anti-PD(L)1 group compared to the chemotherapy alone group. In addition, ctDNA collected later (7-13 weeks) showed stronger associations compared to ctDNA collected up to 7 weeks post-randomization, though the trend was observed at both time points.
The presentation set the stage for the panel discussion by outlining considerations for how ctDNA can be incorporated into clinical trials to enable future meta-analyses that can help validate the use of ctDNA as an intermediate endpoint. The panel was moderated by Charu Aggarwal, Abramson Cancer Center, University of Pennsylvania, with panelists, Zoe June Assaf, Genentech, A Member of the Roche Group, David Fabrizio, Foundation Medicine, Inc., Leon Freytor, Johnson & Johnson, Anand Pathak, U.S. FDA, Carol Vallett, Patient Advocate, and Paz Vellanki, U.S. FDA. Panelists outlined recommendations for implementing ctDNA as an intermediate endpoint, emphasizing transparent data management, assay validation, and alignment of sampling with treatment cycles. Discussions underscored the need for harmonized, sensitive ctDNA assays that can reliably detect change and the need for analytic validation studies. Panelists recommended using at least two time points to assess ctDNA, discussed the impact of using different metrics for molecular response categorization, and noted how meta-analyses could help establish appropriate cut-offs for evaluating ctDNA in various disease settings and therapies. The panel explored using ctDNA as a predictive tool in early-stage cancer and as a complementary endpoint to imaging in advanced settings, with the possibility of expediting drug approvals. Dr. Vellanki noted FDAs interest in seeing ctDNA data from sponsors, even in preliminary forms, as it can provide insights into potential applications and sponsors’ thought processes. The panel underscored the promise of using ctDNA for advancing precision oncology, with a call for further data to solidify its role in tracking and predicting cancer treatment outcomes.
We look forward to continued collaboration to advance these efforts. For more on our Annual Meetings visit here. To learn more about our upcoming meetings and register click here.
