Association of baseline clinical factors and treatment-related variables with survival in phase I solid tumor trials.

Abstract

11039 Background: Phase I trials in solid oncology increasingly use biomarker-based enrollment and evaluate diverse therapeutic mechanisms. However, outcomes among patients with advanced solid tumors remain heterogeneous, and the relative contribution of baseline patient factors versus treatment-related variables to survival is incompletely defined. Methods: We conducted a retrospective analysis of patients with advanced solid tumors treated on Phase I clinical trials in UCLA’s Drug Development Program between Jan 2013 and Sept 2025. Outcomes included objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), and overall survival (OS). Survival was estimated using the Kaplan–Meier method. Multivariable Cox proportional hazards models identified factors independently associated with OS, adjusting for clinical variables, treatment characteristics (including combination vs monotherapy, mechanism of action [MOA] of study therapy, and participation in biomarker-selected trials vs unselected patients), and baseline laboratory values. Results: 726 patients were included across 106 trials. ORR was 13.3%, and DCR was 61.7%. Median PFS was 2.9 months (95% CI 2.66–3.39), and median OS was 10.4 months (95% CI 9.15–12.34). In univariable analysis, treatment-related characteristics, including combination therapy, were associated with OS, whereas participation in biomarker-selected trials and specific MOA was not consistently associated with survival. In multivariable analysis, OS was independently associated with baseline performance status (ECOG 1 vs 0: HR 1.35, 95% CI 1.12-1.63, p = 0.0015), combination therapy (HR 0.81, 95% CI 0.68-0.98, p = 0.0283) and female sex (HR 0.79, 95% CI 0.65-0.96, p = 0.0164). Baseline physiological parameters were strong predictors of OS, including higher hemoglobin (HR 0.90 per 1g/dL increase, 95% CI 0.85-0.96, p = 0.0018), higher albumin (HR 0.48 per 1g/dL increase, 95% CI 0.38-0.61, p < 0.0001), and higher lymphocyte count (HR 0.75 per 1.0K/µL increase, p = 0.0005). Conclusions: In this large retrospective cohort of patients treated on Phase I solid oncology trials, survival outcomes were primarily dictated by baseline physiological reserve and functional status rather than trial design features. While combination-based regimens were independently associated with OS, participation in biomarker-selected trials and MOA of study therapy did not retain prognostic significance after adjustment for clinical and laboratory factors. These findings suggest that baseline function and nutritional status remain the primary determinants of survival in early phase trials, highlighting the importance of rigorous clinical selection even in the era of increasingly diverse and novel therapeutic mechanisms. Ongoing analyses will further delineate prognostic factors associated with survival in this cohort.