Precision Signals: James Gulley, MD, PhD

Endpoints, Resistance, and the Architecture of Evidence in Immuno-Oncology

Immunotherapy has transformed the landscape of oncology, but many of its scientific and structural challenges remain unresolved.

In this episode of Precision Signals, I sat down with Dr. James Gulley, Chief of the Medical Oncology Service and Co-Director of the Center for Immuno-Oncology at the US National Cancer Institute. Dr. Gulley has been at the forefront of immuno-oncology for decades—helping move immune-based therapies from early skepticism to clinical reality while also shaping the frameworks that govern their evaluation and approval. I’ve had the privilege of working with Dr. Gulley across multiple domains, from the early development of immunotherapies to efforts integrating AI into clinical research.

At each inflection point in oncology, Dr. Gulley has brought a systems-level perspective that links mechanistic insight with operational execution, and scientific rigor with institutional change. Whether developing adaptive clinical trials or reimagining evidence generation and real-time data capture with machine learning, his work reflects a sustained commitment to redefining what translational and clinical research can achieve—and what it should require of us.

Our conversation traces the field’s evolution from first-in-human trials to today’s adaptive, biomarker-driven studies. We examine the limits of predictive biomarkers, the complexity of resistance mechanisms, and the inadequacies of current trial designs. We also discuss the need for new endpoints and evidence hierarchies that reflect patient heterogeneity more faithfully.

We also explore how AI-enabled protocol generation, wearable-derived physiologic monitoring, digital pathology, and EHR-integrated data flows are beginning to reconfigure translational infrastructure. Dr. Gulley shares insights from recent work using continuous monitoring to detect CAR-T toxicity before it manifests clinically—an example of how next-generation research tools are converging with real-world care.