Overview
Trillions of microorganisms within the human body profoundly influence health and disease therapeutic outcomes. Developing novel microbiome-based therapies, such as probiotics, prebiotics, diet, defined microbial consortia, engineered bacteria, microbiota-derived proteins and metabolites and fecal microbiota transplantation (FMT) has been the area of extensive research. However, due to many variables and confounding factors, advancing these interventions from preclinical to clinical trial has been challenging and requires transdisciplinary collaborations and rigorous evaluation of safety and effectiveness.
NCI hosted the first timely strategic workshop focused on rigor and reproducibility issues of FMT and microbiome-based cancer therapeutics in 2019, which has recognized the challenging and promising potential of FMT as a novel type of cancer therapeutics and warranted more well-designed larger coordinated clinical trials for many cancer types with ultimate goal toward defined consortia (https://dctd.cancer.gov/NewsEvents/20191031_reproducibility_of_fecal_microbiota_transplants.htm).
NCI is hosting it's “2nd NCI/NIH- Microbiome-targeted Intervention Clinical Research Workshop” virtually on March 5-6, 2024 which will highlight the most recent emerging science and advances in the field, including the results from 2021 first-in-human pilot trial of FMT-improved response to immune checkpoint inhibitors in melanoma patients, which was funded by NCI (1R01CA222203-01A1) in 2018. The FDA has approved the 1st microbiota-based therapy for C. difficile infection in 2022 (https://www.fda.gov/vaccines-blood-biologics/vaccines/rebyota), and the 2nd product in 2023 (https://www.fda.gov/news-events/press-announcements/fda-approves-first-orally-administered-fecal-microbiota-product-prevention-recurrence-clostridioides). This timely 2024 meeting will bring together national and international experts including scientists, physician scientists and FDA regulatory experts in the fields of FMT, pre/probiotics, nutrition, microbiome, epidemiology, bioinformatics and computation, cancer biology, immunology, neuroscience, bioengineering, gastroenterology, oncology, infections, neurological diseases, mental health and behavior science, and drug development.
Purpose:
To accelerate translational and clinical research for developing precision microbiome-targeted interventions for cancer and other diseases.
Objectives:
- Evaluate the science and best research approaches of microbiome-targeted interventions in mechanistic and translational clinical research.
- Discuss research needs and opportunities for harmonization, standardization, and collaboration to enhance the rigor and reproducibility of research on the safety and effectiveness of microbiome-targeted interventions.
Sessions and Key Suggested Discussions:
Session 1: Microbiome Measurements, Bioinformatics and Computation Analysis
- What are the best practices, approaches, tools, and methodologies to enhance research rigor and reproducibility in microbiome measurement and computational analysis for cancer and other diseases?
- What are the challenges for the next steps in developing SOPs? How to overcome?
Session 2: Preclinical Research and Models
- How do we go beyond correlative studies of microbiome and cancer?
- How to take advantage of preclinical models to better understand specific mechanisms of how specific bacteria or bacteria consortia that impact cancer etiopathogenesis and cancer therapies?
Session 3: Translational and Clinical Research
- What is the best approach to developing therapeutic microbiome-targeted interventions for clinical trials for cancer and other diseases?
- What is the current best evidence supporting the most promising interventions advancing to clinical trials, e.g. FMT or defined microbial product? What are the challenges?
- What are the best practices in clinical trial study design, specimen collection, biological measurement and assay, eligibility criteria, inclusion of diverse racial and ethnic populations, determination of primary and secondary endpoints, statistical power calculation, and selection of biomarkers for patient selection?
- What are the best approaches to data collection for variables and confounding factors, and how can AI be developed for microbiome-targeted intervention development, mechanistic research, and clinical trials?
Session 4: FDA Clinical Trial Design and Clinical Regulatory Policy/IND: FMT and LBP for Cancer and Other Diseases
Session 5: Final Panel Discussion and Summary
- Summarize the challenges and provide actionable recommendations for developing a strategic framework for the next 5 and 10 years: how to overcome pitfalls and effectively advance the rigor and reproducibility of preclinical and clinical research in developing precision microbiome-targeted interventions for cancer and other diseases through harmonization, standardization, and collaboration in the era of precision medicine and AI.
- What are the best practices, approaches, tools, and methodologies to enhance research rigor and reproducibility for microbiome measurement and computational analysis from population studies, preclinical mechanistic and translational research to clinical trials in cancer and other diseases?
- What are the best practices and approaches to enhance research rigor and reproducibility for preclinical and clinical research to inform the best clinical trial design?
- What are the best practices and approaches in conducting clinical trials to enhance success and improve healthcare disparity for microbiome targeted intervention?
- What is the current best evidence for the most promising products of each type of intervention moving forward to phase 1/2, randomized phase 2, or 3 in cancer and other diseases?
- What is the best evidence of the currently most promising interventions to develop potential cancer standard care for improving overall survivor and quality of life?
- What are the best approaches in developing a framework for multi-dimensional data collection of biomarkers, variables, and confounding factors, and for infrastructure of bioinformatic and computational analysis for human research and clinical trials?
- What is the best practice and approach in applying data science and AI to advance microbiome-targeted intervention development and clinical trials?
Conference Contact:
Dan Xi, PhD, NCI; Workshop Planning Chair at xida@mail.nih.gov
Workshop Planning Committee AND Participating Institutes and Agency:
National Cancer Institute (NCI):
Dan Xi, Marco Cardone, Phil Daschner, Nina Lukinova, Mehdi Mesri
National Institute of Allergy and Infectious Diseases (NIAID):
Ryan Ranallo
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK):
R. Dwayne Lunsford
U.S. Food and Drug Administration:
Peter Bross