Biomarker testing enables precise therapeutic decisions, from timely and accurate diagnoses through treatment selection and monitoring. As our medicines and technologies become more sophisticated, capable of curing or controlling disease, we envision a world in which most diseases are cured and no longer a threat to living our best lives. However, widespread patient access to testing is critical to realizing this vision. We need creative solutions and collective efforts.

Antibody-drug conjugates (ADCs) are one of the fastest growing classes of anticancer therapeutics in recent years. The unique design of ADCs, comprising a specific antibody conjugated to a cytotoxic payload via a linker, enables efficient and specific drug delivery to antigen-expressing tumor cells. Trastuzumab deruxtecan is a novel HER2-directed ADC that has been evaluated as a treatment for several HER2-expressing cancers. Here we provide an update on the recent companion diagnostic (CDx) approvals for this novel ADC agent, including the first CDx approval for the HER2-low metastatic breast cancer and the first NGS-based approval for the HER2- mutated NSCLC.

Despite significant challenges, drug companies have been increasing their investment in the discovery and implementation of patient selection biomarkers that focus on non-oncology areas. Outside of oncology, this path is not well paved including in the regulatory space. This talk will highlight the principles for co-development of a CDx with a non-oncology therapeutic product, communication strategies for coordinating investigational CDx tests with the FDA, and will address some of the current challenges for co-drug/device development programs in rare disease and cell and gene therapy programs.

The final frontier for cancer elimination may be early detection. Liquid (usually blood-based) biopsies may potentially identify early-stage cancer, allowing for simple curative interventions. Cell-free DNA, extracellular vesicles, and DNA methylation are transformative cancer screening methodologies. However, critical issues remain: addressing false positives when large populations are screened; optimizing assays for single cancer versus across cancers; assessing impact of lead-time bias on survival impact; and applications in high-versus lower-risk patients.

Precision medicine therapies have demonstrated benefits for cancer patients but are dependent on biomarker results for prescription. Four key barriers to optimal precision oncology treatment exist: Awareness, Availability, Adoption, and Access. Each hurdle will be examined through the lens of how LBx tests in today's healthcare system are well-suited to overcome some, but disadvantaged in other barriers, including examples of clinical utility from PADA-1 and DYNAMIC trials.

This talk will cover how challenges in biomarker testing in the cancer patient population are influencing progress, or lack thereof, in the implementation and promise of appropriate use of targeted, matched therapies in the cancer patient population. This talk will review current issues in the field and opportunities for improving options for patients and clinicians.

Despite the recent progress in the development of new anticancer therapies, many patients do not derive optimal benefit from available therapies and most cancers in the advanced stage remain incurable. Catalyzing the next wave of biomedical breakthroughs requires a paradigm shift in the classification of oncological diseases, moving to more objective methods derived from quantitative assessments closer to underlying mechanisms of disease by leveraging advances in AI and machine learning.