Xilio Therapeutics, Inc. announced that the first patient has been dosed in the company's Phase 1/2 clinical trial evaluating XTX202 for the treatment of solid tumors. XTX202 is a modified form of IL-2 that is designed to localize activity in the tumor microenvironment (TME), with the goal of overcoming the known tolerability challenges of existing IL-2 therapies while achieving enhanced anti-tumor activity. Leveraging its proprietary geographically precise solutions (GPS) platform, Xilio designed XTX202 to be masked with a protein domain to prevent binding activity until the protein domain is cleaved off by TME-associated proteases.

XTX202 is intended to be activated selectively in the TME, resulting in localized anti-tumor activity without dose-limiting toxicities. In preclinical studies, XTX202 exhibited tumor-selective biological activity and anti-tumor activity comparable to aldesleukin, a high-dose IL-2 therapy, at its maximum tolerated dose, while minimizing the severe toxicity observed with aldesleukin. In non-human primate models, XTX202 was well-tolerated at doses up to 10 mg/kg weekly.

The Phase 1/2 clinical trial is a first-in-human, multi-center, open-label trial that will evaluate XTX202 as a monotherapy in patients with advanced solid tumors. The Phase 1 portion of the trial consists of a dose-escalation monotherapy cohort designed to evaluate the safety and tolerability of XTX202 and determine the recommended Phase 2 dose. Following completion of the Phase 1 portion, Xilio plans to initiate Phase 2 expansion cohorts with XTX202 monotherapy evaluating the objective response rate in patients with renal cell carcinoma or melanoma who previously received an anti-PD-1 treatment regimen.

Xilio also plans to initiate one or more additional Phase 1 trials aimed at demonstrating utility of XTX202 in combinations with other agents such as anti-PD-1 agents or tyrosine kinase inhibitors.