Abstract B047: Phase I trial of αvβ3 integrin cytotoxin ProAgio in patients with previously treated advanced pancreatic cancer and other solid tumor malignancies
Authors: Skorupan Nebojsa , Peer Cody J. , Koehler Eve , Steinberg Seth , Trepel Jane B , Figg William D , Liu Zhi-Ren , Alewine Christine 
Published: December 2023

Background: ProAgio is a pegylated peptide drug that targets and kills cells that express integrin αvβ3 including cancer associated fibroblasts (CAFs) and endothelial cells within the tumor microenvironment. ProAgio utilizes a novel binding site to directly trigger apoptosis of target cells in pre-clinical models. Here we describe the interim results of a first-in-human phase 1 trial of ProAgio in patients with advanced solid malignancies, including pancreatic cancer.

Methods:  The trial is enrolling adults with previously treated and histologically confirmed advanced solid malignancy for which no curative therapy exists. The dose escalation cohort uses a modified 3+3 design to determine the recommended phase 2 dose (RP2D) of ProAgio. This will be followed by a dose expansion cohort which will enroll only participants with non-neuroendocrine advanced pancreatic cancer. The primary objective of the trial is to determine the RP2D of ProAgio. Secondary objectives assess the safety (CTCAE v. 4.03), pharmacokinetics and objective response rate (ORR) of Proagio. Ascending doses of ProAgio were administered as an intravenous infusion every 1-2 weeks depending on dose level. Response is determined by serial imaging (CT or MRI) and tumor marker assessment (CA 19-9 or appropriate tumor-specific marker). Exploratory objectives include assessing biologic effect of ProAgio on pre- and on-therapy tumor biopsy specimens (apoptosis of tumor cells, integrin αvβ3 expression, CAF population, tumor vasculature and architecture), as well as identifying putative surrogate circulating biomarkers (circulating αvβ3 expressing cells among others).

Results: Sixteen participants (14 with pancreatic adenocarcinoma and 2 with other gastrointestinal malignancies) have been treated on the dose escalation as of June 30, 2023. Preliminary pharmacokinetic measurements demonstrate a plasma half-life of 17.35 hours, distribution volume of 17.62 L, and clearance of 0.522 L/hr. ProAgio has been exceptionally well tolerated with only transient grade 1 or 2 treatment-related adverse events observed in most participants. Two participants had grade 2 infusion related reaction but were able to continue treatment with increased dose of diphenhydramine pre-medication. A serious adverse event of grade 3 hyperglycemia was observed in 1 participant with insulin-dependent diabetes within 24 hours of ProAgio infusion. No other treatment-associated hyperglycemia has been observed. Two participants with pancreatic cancer receiving weekly dosing of ProAgio had stable disease for &gt;4 months and interval stabilization in CA 19-9 tumor marker.

Conclusions: ProAgio is safe and well-tolerated. Upon completion of the dose escalation, a dose expansion phase of 15 participants treated at the RP2D will begin enrolling. NCT05085548

Citation Format: Nebojsa Skorupan, Cody J. Peer, Eve Koehler, Seth Steinberg, Jane B Trepel, William D Figg, Zhi-Ren Liu, Christine Alewine. Phase I trial of αvβ3 integrin cytotoxin ProAgio in patients with previously treated advanced pancreatic cancer and other solid tumor malignancies [abstract]. In: Proceedings of the AACR-NCI-EORTC Virtual International Conference on Molecular Targets and Cancer Therapeutics; 2023 Oct 11-15; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2023;22(12 Suppl):Abstract nr B047.