Adcentrx Therapeutics has announced the dosing of the first patient in a Phase 1a/b clinical trial evaluating ADRX-0405, a novel antibody-drug conjugate (ADC) targeting Six-Transmembrane Epithelial Antigen of the Prostate 1 (STEAP1), for the treatment of advanced solid tumors. This first-in-human trial aims to characterize the safety and tolerability of ADRX-0405 and determine its optimal dose, potentially addressing unmet needs in STEAP1-expressing cancers like metastatic castration-resistant prostate cancer.
Trial Design and Objectives
The Phase 1a/b trial is an open-label, dose-escalation and dose-expansion study being conducted across multiple sites in the United States. The trial is enrolling patients with select advanced solid tumors. The primary objectives include assessing the safety and tolerability of ADRX-0405 and determining the optimal dose for further clinical development. Initial data from the trial is anticipated in the fourth quarter of 2025.
ADRX-0405: A Novel ADC
ADRX-0405 is a next-generation ADC composed of a humanized IgG1 antibody targeting STEAP1, a cell surface protein that is upregulated in prostate cancer and certain other cancers, while exhibiting limited expression in normal healthy tissue. Adcentrx’s proprietary i-Conjugation technology platform plays a crucial role in the design of ADRX-0405. This platform utilizes protease-cleavable linkers and stable conjugation chemistry to enhance payload delivery, ensuring a highly stable ADC with a topoisomerase inhibitor payload conjugated at a drug-to-antibody ratio of eight (DAR 8).
Preclinical Evidence
Preclinical studies of ADRX-0405 have demonstrated favorable pharmacokinetics, a promising safety profile, and significant efficacy across multiple tumor models. These findings support the clinical investigation of ADRX-0405 as a potential first-in-class therapy for STEAP1-expressing cancers.
Executive Perspective
Hui Li, Ph.D., founder and chief executive officer of Adcentrx, stated, "Advancing our second program into clinical trials marks an important milestone for Adcentrx and further validates the potential of our ADC technology platform. STEAP1 is an attractive ADC target, and we are excited about the first-in-class potential for ADRX-0405. We believe this novel ADC offers a unique approach to treating patients with STEAP1-expressing cancers, such as metastatic castration-resistant prostate cancer, where a significant unmet need remains for new targeted therapies."
