First in Human Trials of ProAgio, a Cytotoxin

Abstract public domain (NIH RePORTER)

AIM1 (ongoing): Test safety and pharmacokinetics (PK) of ProAgio in patients. A Phase I clinical study at the NIH Clinical Center was initiated in previously treated patients with advanced solid tumor malignancies (PI Alewine). Patient accrual began in 12/2021 and accrual to the dose escalation phase of the study completed January 2024 (n = 29) with identification of ProAgio single agent RP2D. Accrual of the dose expansion phase of the study (including biopsy cohort) is ongoing. AIM 2 (ongoing): Identify the specific cell subsets in the PDAC TME that are targeted by ProAgio and characterize its effect on TME structure over time. Our current data indicate that short-course ProAgio treatment does not deplete PDAC TME cell subsets that express integrin alphaV-beta3 despite causing significant retardation of tumor growth in an autochthonous mouse model of PDAC. These data have been presented at the AACR Special Conference on Pancreatic Cancer. We are continuing to study the affect of ProAgio on the murine PDAC TME after longer courses of treatment and anticipate submission of a manuscript later in 2024. AIM 3 (ongoing): Assess bioactivity of ProAgio in patients. Tumor biopsy samples are being collected from patients on the ProAgio study. Correlative studies to assess ProAgio effect on stromal density, blood vessels and tumor cellular components will begin when all samples are collected.