Challenges and Considerations in Designing and Conducting Immuno-Oncology Clinical Research

A dynamic landscape: Harnessing the immune system to treat diseases is a new approach that is seeing increased use, particularly in the field of oncology. According to an October 2018 report from The Cancer Research Institute (CRI) titled: “Trends in the Global Immuno-Oncology Landscape” and published in Nature Reviews Drug Discovery, the number of active agents in immuno-oncology ranging across multiple immunotherapy approaches increased 67% in a single year.

The most promising approaches currently include:

• Checkpoint inhibitors
• Adoptive cell transfer including CAR-T cells
• Monoclonal antibodies or therapeutic antibodies
• Treatment vaccines
• Cytokines
• Oncolytic viruses
• Combination therapies

Clinical Trial Considerations: Given the accelerating pace of I-O clinical research, awareness of the specific challenges and considerations in designing and conducting successful trials for these new agents is critical. Join experts from Medpace’s medical department, central lab, and imaging core lab in an interactive discussion that reveals lessons-learned, best practices and the importance of considering the most appropriate biomarkers, safety testing, and imaging needs early in the planning process.

Key topics for discussion will include:

1. Medical and operational considerations:

Clinical trials of immunotherapeutic agents have different considerations for successful execution than standard anti-cancer agents. As novel targets and methods of delivery are identified, investigators need to be aware of the effects on the immune system, including both immunosuppression and autoimmunity, especially as combination therapies are studied. Cellular therapies are known to have unique challenges with scheduling, manufacturing and toxicities. Immunotherapeutic trials have distinctive issues to be addressed regarding patient selection, pharmacokinetics, trial monitoring, toxicity grading, and response assessment.

Applying experience from managing numerous I-O clinical studies, discussion will cover how to successfully address these issues by:

• Carefully considering eligibility criteria
• Designing timely site communication
• Maintaining research subject calendars
• Employing standard guidelines developed for the assessment of disease response and toxicities

2. Biomarkers and testing considerations:

The goal of I-O biomarker development is to enable a more personalized approach to treatment by identifying patients who are likely to respond to specific immunotherapies. I-O biomarkers seek to characterize the relationship between the immune system, the tumor and its microenvironment, and the host. Unique interactions of these factors, as well as I-O biomarker presence and prevalence, contributes to the balance of activation versus suppression of the antitumor immune response.

I-O biomarkers that address this interplay between the immune system and the tumor belong primarily to four key areas. Each of these will be discussed:

• Tumor antigens
• Inflamed tumor markers
• Immune suppression markers
• Host environment factors

3. Imaging considerations:

Imaging poses challenges in trials of immunotherapies as well. In most oncology clinical trials, tumor response occurs between 8 and 12 weeks. With I-O agents, response may be delayed and pseudo-progression has been described. This may provide a false assessment of progressive disease. Newer radiographic staging systems have been developed for solid tumors and lymphomas, taking this observation into consideration. Discussion will cover the following topics accompanied with images to illustrate modalities and measurement criteria:

• Types of imaging that are useful as end-points in immuno-oncology trials
• I-O imaging-related response criteria including Response evaluation criteria in solid tumors (RECIST), irRC, irRECIST, and iRECIST
• Nuclear medicine imaging and I-O response criteria including PERCIST and Lugano
• Optimization of database structures for imaging endpoints in I-O trials including how to structure EDC and eCRF

Speakers

Gregory Hale, MD, Senior Medical Director, Hematology & Oncology, Medpace

Dr. Gregory Hale is a physician with over 26 years of experience in all phases of clinical development, with expertise in hematopoietic stem cell transplantation, cellular and gene therapies and immuno-oncology. Dr. Hale has served as clinical director of the Transplant and Gene Therapy Program at St. Jude Children’s Research Hospital and medical director of the Division of Hematology/Oncology at Johns Hopkins All Children’s Hospital. Most recently he was Professor of Oncology at Johns Hopkins and has authored more than 200 peer-reviewed manuscripts, review articles and book chapters. He has held leadership positions in the National Marrow Donor Program (NMDP) and the Center for International Blood and Marrow Transplant Registry (CIBMTR). 

He earned his medical degree from the Joan C. Edwards School of Medicine at Marshall University. He completed his pediatrics residency at Children’s Hospital of Pittsburgh and his pediatric hematology/oncology fellowship at St. Jude Children’s Research Hospital.

Message Presenter

El Mustapha Bahassi, PhD, Associate Director, Clinical Laboratory, Medpace

Dr. El Mustapha Bahassi is a research scientist with over 20 years of clinical and research laboratory experience. He is experienced in biomarker development and well-versed in various molecular biology techniques such as DNA cloning, PCR, protein purification, mass spectrometry, flow cytometry, mouse modeling, mammalian/bacterial cell culturing, and cell-free DNA/circulating tumor cells manipulation. 

He received his PhD in Molecular Biology and Biotechnology from the University of Brussels in Belgium. He then joined the University of Texas Southwestern Medical Center in Dallas as a postdoctoral fellow in Molecular Oncology. Following his training at UT Southwestern, Dr. Bahassi moved to the Department of Cancer Biology at the University of Cincinnati and later became a faculty member in the Division of Hematology/Oncology. As an independent faculty, Dr. Bahassi developed a translational line of research where he worked closely with clinical oncologists to develop new companion diagnostics using cutting-edge genomic technologies.

Message Presenter

Jess Guarnaschelli, MD, Medical Director, Hematology & Oncology, Medpace

Dr. Jess Guarnaschelli has 15 years of experience in clinical oncology. She is board-certified in radiation oncology, with clinical experience in numerous indications including breast cancer, gynecologic cancers and other adult solid tumors. Prior to joining Medpace, she was an assistant professor at the University of Cincinnati College of Medicine. During her academic career, she focused on novel treatments and supportive care methods for patients with solid malignancies. She was the principal investigator of multiple oncology clinical trials and received numerous funding awards. She has held nationally recognized leadership positions and is a frequently invited speaker at national and international conferences. Locally, she was the moderator of the University of Cincinnati breast tumor board for four years and now remains active in boards and advisory committees focusing on women’s cancer initiatives. 

Dr. Guarnaschelli received her BA in Biology at Brown University and her MD from the University of Louisville School of Medicine.

Message Presenter