OCE Scientific Interest Areas

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Cell/gene and personalized neo-antigen-based therapies for cancer

Cell therapy is a promising new form of cancer treatment as demonstrated by recent CAR T-cell therapy approvals. New technologies are enabling rapid manufacturing of cells with tumor-killing capacity, necessitating more efficient clinical evaluation and innovative regulatory approaches.

The science of neo-antigen-based therapies for cancer is also developing rapidly, particularly since advances in genomics and proteomics allow identification of somatic mutations unique to individual cancers. Recent studies have demonstrated that high levels of somatic tumor mutations are correlated with response to immunotherapies such as checkpoint inhibitors, suggesting that individual tumor mutations (neoantigens) could be harnessed for immune targeting to develop personalized therapies such as cancer vaccines and cell therapies that target these neoantigens.

OCE is interested in supporting research related to clinical development, safety, manufacturing and quality control for cell therapy and neo-antigen-based therapies for cancer. Example OCE research interests in this scientific priority area include:

Create novel technologies and approaches to evaluate both efficacy and safety for neoantigen-based therapies that incorporate unique features of individual cancers, neoantigen and immune responses. Examples may include neoantigen-based vaccines redirecting the T-cell specificity by genetically modifying T cells with receptors specific against neoantigen-derived epitopes. (BAA Charge I.B.2.)
Develop, optimize and standardize bioinformatic algorithms for neoantigen identification and development of personalized therapies. These are important to ensure the efficacy and safety of these products in the treatment of patients with cancer. (BAA Charge I.C.2.)
Develop innovative trial designs (e.g., master protocols) for a group of cell or neoantigen-based therapies that were developed using a common platform (but target distinct antigens) to compare safety and clinical activity among products to identify the most promising candidates for further development. (BAA Charge I.F.1.)
Develop innovative clinical trial designs to establish safety and efficacy in cell and gene therapies in randomized clinical studies where feasible. (BAA Charge I.F.1.)

Immuno-oncology

Immune checkpoint inhibitors (ICI) have become the standard of care for more than 25 types of cancer and offer long-term disease control. Unfortunately, a large proportion of patients do not respond or become resistant to these treatments. There is a high unmet need to develop therapeutics for ICI-refractory or resistant patients.

Example OCE research interests in this scientific priority area include:

Understanding tumor biomarkers (e.g., spatialomics, transcriptomic, proteomic analyses) that would predict subsequent radiologic and clinical outcomes (e.g., prolonged stability/ subsequent response vs. continued progression) in patients who have radiologic progression without signs of clinical progression that allows for discretionary continuation of current immune-checkpoint inhibitor therapy (BAA Charge I.C.2.)
Further characterization of molecular mechanisms of immunologically cold tumors that could potentially translate into therapeutic interventions (BAA Charge I.C.2.)

For more information, see the Immuno-Oncology Program.

Oncology patient-focused drug development

Patients with cancer experience disease symptoms and symptomatic treatment side effects that can impact their ability to function and other aspects of their health-related quality of life. OCE is interested in supporting research focused on developing approaches to assess the patient experience that will complement existing survival and tumor information. These concepts and core domains are well described in the FDA Core Patient-Reported Outcomes in Cancer Clinical Trials Final Guidance.

Symptomatic adverse events and overall side effect impact are critically important to patients, and improved analysis and visualization of symptomatic adverse events is a priority. In addition, the OCE is interested in exploring the utility of a single overall side effect global impact question that can be used to summarize overall side effect burden.

Physical function is another important patient-centered outcome that is a focus area of OCE research efforts. In particular, OCE is interested to learn more about the impact of different technologies, recall periods and different data collection platforms for gathering physical function data in oncology clinical trials.

Example OCE research interests in this scientific priority area include:

Investigate the sensitivity and measurement characteristics of existing patient-reported or digitally-derived physical function measures in patients with rare and ultra-rare cancers (BAA Charge I.E.1.)
Investigate open label bias: evaluate the impact of patient knowledge of their treatment on patient-reported outcomes in cancer clinical trials (BAA Charge I.E.1.)
Study existing methods and develop novel methods to measure patient-reported symptomatic ocular toxicity in patients receiving anti-cancer therapy (BAA Charge I.E.1.)

For more information, see the Patient-Focused Drug Development Program.

Oncology safety

Many advances have been made in the treatment of cancer with an increasing number of treatment options available to oncology patients. With the introduction of newer treatment approaches, patients and providers are faced with unique new toxicities and challenges associated with their management. Many cancer patients are living longer and are being exposed to multiple lines of cancer therapy which increases morbidity from toxicities.

Some toxicities are acute while others become chronic. Often, the safety profile of oncology drugs is not fully defined until the drug is administered to a large population of 'real-world' patients with comorbidities that were not included in a clinical trial, or until long-term follow-up uncovers late-onset toxicities or additional exposure uncovers rare serious toxicities. The natural trajectory and long-term outcome, as well as the underlying mechanisms of many toxicities, is not well understood. There are no clear predictors of risk factors for most of these toxicities and why they vary in severity and duration from one individual to another.

There is a lack of mechanistic insight into these adverse events, difficulties in objectively measuring treatment-related toxic effects and insufficient studies validating pre-clinical biomarkers in the clinical setting.

Example OCE research interests in this scientific priority area include:

Develop improved and standardized approaches to collect serious toxicities such as cytokine release syndrome and neurotoxicity across a drug class, e.g., bispecific T cell engagers (BAA Charge I.J.2.)
Develop and validate AI based approaches for collecting and analyzing safety data from RWD sources to expand understanding of the safety profile of approved oncology products in clinical practice and post approval (BAA Charge II.A.2.)
Develop novel approaches to utilizing AI/ML to mine different data sources (e.g., EHRs, claims data, clinical trial data) for safety signal identification (BAA Charge II.B.2.)
Develop and validate models and/or new translational study designs to better understand the mechanisms of toxicity observed with recent new drug approvals e.g.: ADCs and ophthalmological toxicity (BAA Charge II.C.2.)
Develop AI based tools and/or algorithms to identify immune-related adverse events observed with immune check point inhibitors to eliminate the need for manual adjudication (BAA Charge II.D.2.)
Develop improved and standardized approaches to collect and analyze cardiotoxicity data in the context of clinical trials to support new indications (BAA Charge I.J.2.)
Analyze RWD to help understand which patients are most likely to experience cardiotoxicity (or other types of severe toxicity) during cancer treatment (BAA Charge II.A.2.)
Develop improved and standardized approaches to collect and analyze cardiotoxicity data in the context of post approval clinical trials and clinical practice (BAA Charge II.C.2.)
Conduct basic, translational or clinical studies that investigate the underlying causes of cardiac toxicities associated with approved oncology agents (BAA Charge II.C.2.)

Oncology trial designs, endpoints and statistical methodologies

OCE provides detailed advice to sponsors about appropriate clinical trial designs, including statistical analysis methods. Rapid technological developments have increased sponsors’ interest in developing novel endpoints and interest in using data sources other than information collected during traditional clinical trials to support regulatory submissions.

Example OCE research interests in this scientific priority area include:

Pediatric oncology

The development of drugs for children and adolescents with cancer is highly complex and involves unique biological, clinical, societal, and economic challenges. Pediatric drug development usually leverages efforts in adult drug discovery and development. Recent observations made possible through large scale pan-cancer genomic profiling across multiple pediatric cancers suggest that more than 50% of childhood cancers express druggable (approved, targeted drugs available) molecular aberrations. However, some targeted agents developed for adults are not effective in children. For example, immune checkpoint inhibitors have transformed treatment for several adult cancers but are less effective in most pediatric cancers because of diminished neoantigen expression due to low mutational burdens. Insufficient availability of appropriate preclinical models for pediatric cancers is also a major obstacle to advancing the field and is critical to identify promising molecular therapeutic products, particularly immunotherapies and other complex biological products, for pediatric cancers.

Examples of OCE research interests in this scientific priority area include:

For more information, see the Pediatric Oncology Program.

Precision oncology

Implementation of precision oncology has grown rapidly, with dozens of gene- and protein-based markers used to define enrollment criteria for oncology clinical trials and included in drug labels as companion or complementary diagnostics, pharmacogenomic or safety markers. There is a continued need to further understand the role of biomarkers in oncology including predicting response to treatment, understanding disease progression and resistance mechanisms, and identifying high risk populations.

Several exciting technologies are advancing precision oncology, including measuring molecular changes in circulating tumor DNA isolated from plasma, and radiomics, an emerging science that uses algorithms to extract features from medical images that are invisible to the human eye. Combined with advanced machine learning algorithms, radiomics can improve disease detection, characterization, staging, as well as assessment and prediction of treatment response. A related field, radiogenomics, assesses the relationship between imaging features and gene expression. Work in this area is advancing rapidly since extensive imaging and genomic information are routinely collected in oncology clinical trials.

Example OCE research interests in this scientific priority area include:

Identify and explore approaches to validate biomarkers (including liquid biopsy and multiomic biomarkers) that capture the dynamic nature of cancer and treatment resistance, including for treatment escalation/de-escalation in the neoadjuvant, adjuvant, advanced and recurrent disease settings. (BAA Charge I.D.2.)
Conduct studies to compare the analytical and clinical performance of local and centralized molecular tests used for patient enrollment on cancer clinical trials (BAA Charge I.D.2)
Develop novel selection/response biomarkers using algorithms combining different types of medical images including radiology images (e.g., CT, PET) and/or histopathology images combined with novel analysis approaches such as radiomics and artificial intelligence/machine learning (BAA Charge I.C.2.)
Conduct studies to understand why tumors originating from different organ sites with molecular alterations in the same target respond differently to therapies to inform future potential tumor agnostic drug development (BAA Charge I.D.2.)
Studies, including registries, to understand the epidemiology and rates of biomarker testing in patients with cancer, such as studying the prevalence of rare genomic subsets of clinical interest in patients with cancer (BAA Charge I.J.2.)

For more information, see the Precision Oncology Program.

Rare cancers

Identifying candidate drugs and testing their effects in rare populations can be challenging and time consuming. Investigating approved drugs potentially offers a more efficient pathway for drug development for rare cancers. Use of decentralized elements in clinical trials including telemedicine and incorporation of other pragmatic features into clinical trials are also areas of interest for OCE but have not been widely implemented.

OCE is interested in supporting research to assist drug development for rare cancers, including molecularly defined subsets (e.g., RET-positive lung cancers and KRAS-mutated low grade serous ovarian cancer) of more common tumors, and all pediatric cancers such as:

For more information, see the Rare Cancers Program.

Oncology Real-World Data and Real-World Evidence

Developing approaches to evaluate, integrate, and facilitate the use of oncology real world data (RWD) (e.g., electronic health records, administrative health claims, drug or disease registries, patient reported or generated health data) to generate high-quality real-world evidence (RWE) is an active area of regulatory science as noted in the 21st Century Cures Act.

Methodologically rigorous research which expands upon the need to evaluate innovative study approaches such as clinical trials including pragmatic elements, or other prospective designs including development of RWD resources through high quality registry studies to accelerate clinical development of new drugs in oncology are encouraged. Specific examples of interest are included in the immuno-oncology, oncology trial designs, endpoints and statistical methodologies, pediatric oncology, oncology safety, and rare cancers sections.

Evaluation of innovative applications of RWD to clinical drug development, including epidemiologic and statistical approaches, specifically scientific methods research to enhance evaluation and assessment of RWD through evaluation of bias, confounding, or other potential threats to study validity. Examples include investigations to explore appropriate uses of externally controlled designs in clinical drug development (BAA Charge I.J.2.)
Explore and define RWD quality through a research study or framework development to consider factors including data reliability and relevance including (but not limited to) factors such as collection missingness, specificity, sensitivity, data validation, data harmonization, data provenance, interoperability, data linkage, and the potential capability to make accurate inferences from the available data or improve standardization efforts in the source data towards learning healthcare systems (BAA Charge I.J.2.)
Develop, define and test real world endpoints from oncology RWD that could be used to generate real world evidence (RWE) to complement traditional clinical trial data submitted to FDA, particularly the development of measures of real-world response (BAA Charge I.J.2.)

For more information, see the Oncology Real World Evidence Program.

Further Information