Phase I study of ProAgio, an αvβ3 integrin cytotoxin, in patients with previously treated advanced pancreatic cancer and other solid tumors.

Abstract

e16336 Background: The limited clinical benefit of combination chemotherapy in patients with advanced pancreatic cancer is in part attributed to the tumor’s dense, hypoxic stroma that is largely composed of extracellular matrix, cancer-associated fibroblasts (CAFs), and myeloid cells. ProAgio is a pegylated peptide drug that targets and kills cells expressing integrin αvβ3, such as CAFs and endothelial cells. Preclinical activity of ProAgio was demonstrated in murine pancreatic cancer models. Here we describe the dose escalation arm of the first-in-human Phase 1 trial of ProAgio in patients with advanced solid malignancies, including pancreatic cancer. Methods: The dose escalation arm of this single institution study of ProAgio monotherapy enrolled adults with previously treated, histologically confirmed advanced solid tumors for which no curative therapy exists. Participants were required to have evaluable disease. The primary objective was to determine the recommended Phase 2 dose (RP2D) of ProAgio. Secondary objectives assessed the safety (CTCAE v. 4.03), pharmacokinetics, and objective response rate. ProAgio was administered as an intravenous infusion every 1-2 weeks depending on the dose level. Response was determined by serial imaging (CT or MRI) or serum tumor marker assessment. Results: Twenty-eight participants (26 with pancreatic adenocarcinoma and 2 with other gastrointestinal malignancies) were treated as of January 30, 2024, completing enrollment to all 6 planned dose levels. ProAgio has been remarkably 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. Isolated serious adverse events of hyperglycemia, acute kidney injury, or anemia (all grade 3) considered at least possibly related to ProAgio were observed in 3 separate participants. Five participants with pancreatic cancer receiving weekly dosing of ProAgio had stable disease, 2 of which had interval stabilization in CA 19-9 tumor markers. RP2D determination is pending completion of pharmacokinetic analyses. Conclusions: ProAgio is safe and well-tolerated at all dose levels. A dose expansion phase of 15 participants will begin enrolling once RP2D is determined. Clinical trial information: NCT05085548 .