As technologies evolve and regulatory agencies throughout the world change requirements for CDx, pharma companies have to continually adjust their global CDx strategies. In this talk, we will discuss some of the recent changes, challenges and solutions.

Increased focus on targeted patient populations in oncology drug development has led to a rise in the requirement for fit-for-purpose assays that can select the intended patient population in early oncology programs. This creates a need to implement comprehensive strategies for CDx development early on and balance the investment approach with the biomarker complexity and probability of success. Best practices related to these challenges will be reviewed.

Plasma-Safe-SeqS (SafeSEQ), an ultra-sensitive NGS liquid biopsy, can aid cancer drug development, treatment guidance and monitoring, in addition to post-treatment recurrence monitoring. Dr. Fred Jones discusses the clinical value of SafeSEQ by reviewing therapy de-escalation of HPV+ HNSCC patients and monitoring PIK3CA and ESR1 low-level mutations in breast cancer.

Pharma-Diagnostic partnership has become a standard practice for most drug development programs under the Rx/Dx co-development principle. However, successful collaborations often take meticulous planning and execution with flexibility on both ends to overcome constant challenges and deliver on time with highest possible quality for the developed diagnostics. This presentation will highlight some considerations from the pharma perspective at different stages of working with a diagnostic partner.

Recent epidemiological data reported Nonalcoholic Fatty Liver Disease, as one of the most common causes of chronic liver disease in the developing world. Diagnosis of disease severity is an important issue as noninvasive diagnostic biomarker is currently lacking. Analysis of the ABOS cohort led to the stratification of about 800 patients in three distinct groups according to their liver status. A multi-omics analysis was performed from plasma/serum, miRNA sequencing from liver biopsies, RNAseq on a subset of samples from extreme phenotypes with unequivocal diagnosis. Predictive disease biomarker candidates have been identified which are being further validated.

Hybrid capture technology confers a number of advantages over traditional amplicon-based sequencing including increased uniformity, lower error rate, and improved detection of more complex indels. Because of these benefits and the multiple assays used for specific tumor types, the Center for Personalized Diagnostics (CPD) decided to move to a single hybrid capture panel for both solid tumors and hematological malignancies. The CPD joined colleagues who are developing an academic laboratory consortium, the Genomics Organization for Academic Laboratories (GOAL), that was initially developed to improve group purchasing power for the capture probes needed for the development of a larger panel. This talk will discuss the validation parameters for this clinical panel, designed for the detection and reporting of SNVs and indels across the full coding sequence of 116 hematological malignancy-related genes and 183 solid tumor-related genes as well as CNVs in a subset of these genes. Penn plans to participate in GOAL consortium concordance studies to demonstrate laboratories using the shared resources show consistent and reproducible results.

The analysis of tumors using biomarkers in blood is already transforming treatment selection and it may have utility at almost every stage of the management of patients with cancer, including diagnosis, minimally invasive molecular profiling, treatment monitoring, the detection of residual disease and the identification of resistance mutations. The revolution of liquid biopsies will transform the way we do diagnostic testing, but it will also bring important clinical implementation challenges. These challenges include, among others, appropriate analytical and clinical validation, trained lab personnel, multidisciplinary teams’ education and training, results interpretation regulatory approvals, or reimbursement. Machine learning or artificial intelligence may facilitate some of these processes. We will review these and other options to understand how we could accelerate this transformation based on previous learnings. We do need to change our minds; we need to think differently, and this is the necessary step to definitely bring into the clinical practice this important tool.

Over the past two decades, precision medicine has transformed the treatment of cancer by understanding disease biology and targeting treatment appropriately. Using the same approaches we can revolutionize the way that we treat other major diseases – targeting the right medicine to the right patient. In this presentation, I will outline the progress that is being made in this field and the impact that this will have on the future.

Biomarker driven decisions from preclinical research through clinical phases increase the probability of success by the ability to make accurate assessment of treatment and enable optimal clinical management of patients. When each drug discovery project enters the portfolio, a dedicated biomarker strategy is therefore developed. I will present examples on biomarker development in cardiovascular and renal diseases showing how the target engagement can change by mode-of action and modality.

Transformative precision medicine approaches perfectly integrate disease root cause identification, prediction of disease dynamics and medical interventions guided by an advanced understanding of pharmacodynamic up- and downstream effects which allows to optimize and deepen responses at individual patient level. AI/ML powered translational research generated several clinically actionable insights for new targets, early interventions/maintenance settings and combination therapies. Digital pathology, radiomics and advanced clinical genomics platform approaches are key enablers to develop precision oncology break-through therapies.

Circulating exosomes have emerged as means for a multitude of cancer applications including early detection, tumor molecular classification, prediction of therapeutic response, and monitoring of tumor progression and regression. The informative value of circulating exosomes across several types of solid tumors will be presented that are indicative of the value of circulating exosomes as a liquid biopsy approach.

We have developed a functional genomics engine that consists of a multi-interdisciplinary team of clinicians, pathologists and scientists, utilizing the latest comprehensive genomics tools and preclinical models dedicated to improving patient outcomes by tailoring therapy according to the compendium of alterations of the patient’s cancer. Knowledge that is gained by this system leads to novel biomarkers that if validated can be translated to clinical tests in a CLIA environment.