The study evaluated VT1021, a cyclic peptide that induces thrombospondin-1 (TSP-1) expression in myeloid-derived suppressor cells (MDSCs) recruited to the tumor microenvironment (TME). The primary objective was to determine the recommended Phase 2 dose (RP2D) in patients with advanced solid tumors. The trial used a modified 3 + 3 design, with safety, tolerability, and pharmacokinetics (PK) assessed. VT1021 was administered intravenously twice weekly in nine cohorts (0.5–15.6 mg/kg). The RP2D was established at 11.8 mg/kg, with no dose-limiting toxicities reported. Common adverse events included fatigue, nausea, and infusion-related reactions. The disease control rate (DCR) was 42.9%, with one patient achieving a partial response and 11 patients showing stable disease. Biomarker analyses confirmed that VT1021 induced TSP-1 expression in MDSCs and reprogrammed the TME from immunologically cold to hot. The study concluded that VT1021 is safe and well-tolerated, with potential single-agent activity in advanced solid tumors, particularly those with an immunologically cold TME. Expansion studies in GBM, pancreatic cancer, and other solid tumors at the RP2D are ongoing.The study evaluated VT1021, a cyclic peptide that induces thrombospondin-1 (TSP-1) expression in myeloid-derived suppressor cells (MDSCs) recruited to the tumor microenvironment (TME). The primary objective was to determine the recommended Phase 2 dose (RP2D) in patients with advanced solid tumors. The trial used a modified 3 + 3 design, with safety, tolerability, and pharmacokinetics (PK) assessed. VT1021 was administered intravenously twice weekly in nine cohorts (0.5–15.6 mg/kg). The RP2D was established at 11.8 mg/kg, with no dose-limiting toxicities reported. Common adverse events included fatigue, nausea, and infusion-related reactions. The disease control rate (DCR) was 42.9%, with one patient achieving a partial response and 11 patients showing stable disease. Biomarker analyses confirmed that VT1021 induced TSP-1 expression in MDSCs and reprogrammed the TME from immunologically cold to hot. The study concluded that VT1021 is safe and well-tolerated, with potential single-agent activity in advanced solid tumors, particularly those with an immunologically cold TME. Expansion studies in GBM, pancreatic cancer, and other solid tumors at the RP2D are ongoing.