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Updated: Jul 5, 2025
Author Spotlight: Creating Human Vascularized Micro-Tumors as Models for Translational Cancer Research
Published on: September 15, 2023
First-in-human phase I dose escalation trial of the first-in-class tumor microenvironment modulator VT1021 in
Devalingam Mahalingam1, Wael Harb2, Amita Patnaik3
1Northwestern University Medical School, Chicago, IL, USA. Mahalingam@nm.org.
Background:
VT1021 is a cyclic peptide that induces the expression of thrombospondin-1 (TSP-1) in myeloid-derived suppressor cells (MDSCs) recruited to the tumor microenvironment (TME). TSP-1 reprograms the TME via binding to CD36 and CD47 to induce tumor and endothelial cell apoptosis as well as immune modulation in the TME.
Methods:
Study VT1021-01 (ClinicalTrials.gov ID NCT03364400) used a modified 3 + 3 design. The primary objective was to determine the recommended Phase 2 dose (RP2D) in patients with advanced solid tumors. Safety, tolerability, and pharmacokinetics (PK) were assessed. Patients were dosed twice weekly intravenously in 9 cohorts (0.5-15.6 mg/kg). Safety was evaluated using CTCAE version 5.0 and the anti-tumor activity was evaluated by RECIST version 1.1.
Results:
The RP2D of VT1021 is established at 11.8 mg/kg. VT1021 is well tolerated with no dose-limiting toxicities reported (0/38). The most frequent drug-related adverse events are fatigue (15.8%), nausea (10.5%), and infusion-related reactions (10.5%). Exposure increases proportionally from 0.5 to 8.8 mg/kg. The disease control rate (DCR) is 42.9% with 12 of 28 patients deriving clinical benefit including a partial response (PR) in one thymoma patient (504 days).
Conclusions:
VT1021 is safe and well-tolerated across all doses tested. RP2D has been selected for future clinical studies. PR and SD with tumor shrinkage are observed in multiple patients underscoring the single-agent potential of VT1021. Expansion studies in GBM, pancreatic cancer and other solid tumors at the RP2D have been completed and results will be communicated in a separate report.
Insights
VT1021, a cyclic peptide, is safe and well-tolerated in patients with advanced solid tumors. The recommended Phase 2 dose (RP2D) of 11.8 mg/kg showed clinical benefit, including partial response, supporting its potential as a single-agent therapy.
Area of Science:
- Oncology
- Immunotherapy
- Cancer Therapeutics
Background:
- VT1021 is a cyclic peptide that modulates the tumor microenvironment (TME) by inducing thrombospondin-1 (TSP-1) expression in myeloid-derived suppressor cells (MDSCs).
- TSP-1 interacts with CD36 and CD47 to promote tumor and endothelial cell apoptosis and immune modulation within the TME.
Purpose of the Study:
- To determine the recommended Phase 2 dose (RP2D) of VT1021 in patients with advanced solid tumors.
- To assess the safety, tolerability, and pharmacokinetics (PK) of VT1021.
Main Methods:
- A modified 3+3 dose-escalation design was employed in Study VT1021-01 (NCT03364400).
- Patients received intravenous VT1021 twice weekly across 9 dose cohorts (0.5-15.6 mg/kg).
- Safety was evaluated using CTCAE v5.0, and anti-tumor activity was assessed per RECIST v1.1.
Main Results:
- The RP2D was established at 11.8 mg/kg, with no dose-limiting toxicities observed (0/38 patients).
- Common treatment-related adverse events included fatigue, nausea, and infusion reactions (all 15.8% or less).
- A disease control rate (DCR) of 42.9% was observed, with 12/28 patients showing clinical benefit, including a 504-day partial response in a thymoma patient.
Conclusions:
- VT1021 demonstrated a favorable safety and tolerability profile across tested doses.
- The RP2D of 11.8 mg/kg is suitable for further clinical investigation.
- Observed partial responses and stable disease with tumor shrinkage highlight VT1021's potential as a monotherapy.
