The importance of ever-evolving phase 1 trials in oncology

Phase 1 clinical trials are a critical step in oncology drug development. Historically, these first-in-human trials focused on dose–toxicity profiling in heterogeneous populations. With the emergence of novel anticancer therapies, trial design has shifted toward model-based and adaptive dose-escalation designs, improving dose optimization, and now incorporates biomarker-driven patient selection and multiple objectives, including early efficacy assessment, which accelerates drug development. Hence, phase 1 clinical trials have undergone substantial transformation over recent decades, with a marked impact on response rates and phase 1 units that conduct these trials. By transforming early-stage drug discovery and target identification as well as predicting drug efficacy and toxicity, the implementation of artificial intelligence into early-phase cancer research will further accelerate the discovery of novel anticancer drugs and significantly transform today’s phase 1 trials, ultimately resulting in an increase in phase 1 clinical trials in the near future. In this narrative review, we address the importance of clinical phase 1 trials for oncology drug development, highlight their continuous evolution over the past decades to date, and discuss how this affects phase 1 units and their investigators, as well as exploring the impact of artificial intelligence on phase 1 trials in the coming years.