Abstract IA01: Moving phase 1 trials to first-line metastatic disease: Challenges and Opportunities

Abstract First-in-human and phase 1 oncology studies have traditionally been conducted in patients with advanced, late-line disease. However, initiating evaluation of investigational agents in the first-line metastatic setting can confer important advantages in the right context and when supported by biologic rationale and early clinical data. These include expanding trial access, enabling more informative safety assessment, and potentially detecting larger efficacy signals in treatment-naïve populations. In recognition of these opportunities, the U.S. Food and Drug Administration launched Project Front-Runner in 2022 to provide a framework for identifying suitable applications and guiding initiation of development in earlier lines of metastatic disease. This presentation will review the scientific and regulatory rationale for phase 1 trials in this setting and will illustrate implementation of this approach using examples from the Amgen oncology development pipeline. Citation Format: Anna F. Farago. Moving phase 1 trials to first-line metastatic disease: Challenges and Opportunities [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics; 2025 Oct 22-26; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2025;24(10 Suppl):Abstract nr IA01.