Precision Medicine in Early Oncology Trials: Biomarkers as Strategic Drivers

Oncology drug development has shifted decisively towards precision immunotherapies, where biomarker-defined patient populations play a pivotal role. Immuno-oncology now represents one of the most promising frontiers of cancer research, and while the commercial landscape is currently dominated by immune checkpoint inhibitors, several recent approvals of new modalities underline the field’s accelerating progress.

During a recent webinar, immuno-oncology experts at Caidya discussed the potential for novel immunotherapy combinations to further advance this emerging area. It was noted during the webinar that: “The approved immunotherapies still largely rely on immune checkpoint inhibitors, but in the last few years there is an expanding range that now includes CAR-T cell therapy, tumour-infiltrated lymphocytes, bispecific antibodies, cytokines, IL-2 and IL-15 analogues, and oncolytic viruses. We expect that in the coming years this will increase, not only with new immuno-oncology strategies but also with new combinations of these strategies looking for a synergistic effect.”

Later in the webinar, it was mentioned that the future of precision immunotherapies will be driven by two major trends: the first, novel combinations and second, new biomarker strategies.

Why biomarkers matter more than ever

By pairing appropriate treatments with the specific genetic or molecular characteristics of each patient’s tumor, biomarker-driven therapies are the true essence of precision oncology. Biomarkers are now foundational to modern oncology practices, especially given the vast array of molecular subtypes, immune microenvironment variabilities, and other patient-specific factors that are now known to drive unique patterns of tumor development, growth and resistance.

In clinical development, biomarker-driven therapies reduce costly failures by matching the right drug to the right patients, streamlining clinical trials and accelerating approvals. In practice, this means smaller trials with enriched populations, faster signal detection, and more efficient capital use.

While this brings major competitive benefits, it also presents challenges. For therapies targeting a specific biomarker-defined patient population, the FDA generally requires the contemporaneous approval of a companion diagnostic device, or CDx, which analyzes a sample of the patient’s tumor or blood to detect specific biomarkers. Early co-development activities can expedite regulatory submissions and support reimbursement and payer confidence upon market entry, providing clear evidence of patient benefit. However, this significantly complicates timing alignment, analytical validation requirements, and clinical strategies, with a delayed CDx strategy often derailing timelines.

Integrate biomarkers early

Overall, a key piece of advice shared in the webinar was to start building in biomarkers early, aligning target biology to measurable biomarkers from the preclinical stage. “As the industry evolves, it’s really critical to have early integration of biomarkers,” stated Adam Callahan, MS, MBA, Head of Oncology and Hematology at Caidya. During development, he explained that this can ultimately enhance both patient selection and trial efficiency, accelerating overall timelines and reducing costs.

During early trials, biomarkers can also drive dose optimization strategies as the industry moves away from maximum tolerated doses towards biologically optimized ones, in line with recent FDA guidance. CDx-informed dose stratification goes hand in hand with adaptive trial designs as early as Phase I, allowing for mid-course adjustments such as population enrichment or dropping an ineffective or unsafe dose early on.

“Implementing that early and looking at early signal detection becomes more and more critical for enabling decision-making across those inflection points,” Callahan added.

Emerging biomarker modalities and the role of AI

During the webinar, the experts also spent some time discussing emerging biomarker modalities, such as liquid biopsies and next-generation sequencing. One example is the use of circulating tumour DNA (ctDNA) detection for assessing the molecular residual disease in stage I-II colorectal cancer patients, giving a better understanding of the benefits or risks to that patient receiving adjuvant chemotherapy.

The webinar also highlighted the potential of AI integration to further improve decision-making, citing a study in which AI increased concordance in HER2 classification. This may support better patient selection as the range of commercially available targeted therapies for both HER2-high and HER2-low breast cancers continues to expand.

Watch the full webinar here

The critical role of biomarkers in precision oncology was just one topic of conversation during Caidya’s webinar, which provided an in-depth overview of oncology drug development trends, immunotherapy combinations, advanced technologies for reducing cost burden, and strategic trial design considerations.