Evolving phase I oncology trials in the precision medicine era: design, outcomes, and geographic access

Over the past decade, early phase oncology trials have evolved from safety-focused designs to precision-oriented strategies. This study evaluated longitudinal trends, focusing on clinical outcomes, trial design evolution, and the impact of comprehensive genomic profiling (CGP) following its national insurance coverage in Japan in 2019.

This retrospective observational study included patients enrolled in early phase oncology trials at National Cancer Center Hospital (NCCH) between 2016 and 2023. Clinical, molecular, and geographic data were extracted from medical records. Categorical outcomes were compared using chi-square tests. Variables were compared between the early period (2016-2019) and the recent period (2020-2023).

Over 8 years, 1243 patients were enrolled across 1642 early phase trials. The proportion of patients enrolled in genomically matched trials increased significantly from 10.5% in the early period to 28.4% in the recent period (P < 0.0001), in parallel with expanded CGP implementation, which rose from 44.4% to 82.8% (P < 0.0001). The overall objective response rate (ORR) was numerically higher in the recent period (12.6% to 15.9%), with an ORR of 29.1% observed in genomically matched trials. Small-molecule therapies demonstrated a numerical increase in ORR (9.8% to 18.2%), whereas antibody-drug conjugates maintained high ORRs (30.8% to 30.5%). The median travel distance to NCCH increased from 26.6 km to 32.7 km (P < 0.0001), indicating expanded nationwide referral.

The evolving early phase oncology trials, characterized by increased adoption of genomically matched trial designs, broader access to CGP under universal health coverage, and expanded nationwide referral networks, highlight a shift toward more precision in early drug development.