2683 - A phase I open label dose escalation trial evaluating VT1021 in patients with advanced solid tumors.

Background

VT1021 is a cyclic pentapeptide that functions as a potent inducer of thrombospondin-1 (Tsp-1) expression in the tumor microenvironment (TME). By triggering the production of Tsp-1, VT1021 reprograms the TME from one that is immune-suppressive and tumor-promoting, to one that activates the adaptive immune system and is tumor-inhibiting. Tsp-1 reprograms the TME to: (i) induce apoptosis in tumor cells that express CD36 on their cell surface, (ii) convert macrophages from M2 to M1 polarization, which promotes phagocytosis and blunts immunosuppression, and (iii) inhibit angiogenesis. Preclinical studies have shown robust anti-tumor activities of VT1021 in animal models of ovarian, pancreatic and breast cancer, including complete tumor regression and reprogramming of the immune TME.

Methods

This study is a first-in-human, phase 1, open-label, multicenter dose escalation (Part 1) study with dose expansion (Part 2) in advanced solid tumors. The primary objectives are to assess the safety and tolerability of VT1021, assess dose-limiting toxicities (DLT), and determine the maximum tolerated dose (MTD) and the recommended Phase 2 dose (RP2D). Secondary objectives include the evaluation of pharmacokinetics (PK) and the pharmacodynamic (PD) effects of VT1021 in tumor biopsies, and assessment of preliminary efficacy.

Results

In Part 1 of the study, 27 patients received 0.5-6.6 mg/kg of VT1021 twice weekly to determine the MTD and RP2D for expansion. One patient developed a grade 3 infusion reaction and 2 patients developed a grade 2 infusion reaction. Premedication with steroids and antihistamines has prevented subsequent significant infusion reactions. Other drug-related AEs included grade 1-2 fatigue, myalgia and dizziness. Dose proportionality was observed in PK analysis. Evidence of Tsp-1 expression, as measured by IHC on tumor biopsies, was observed. Prolonged stable disease was observed in 2 patients including ovarian and colorectal cancer. In Part 2 of the study, 75 patients will be enrolled based on tumor type and CD36 expression.

Conclusions

Through all doses tested thus far, VT1021 has been shown to be safe for patients and induces expression of Tsp-1.

Clinical trial identification

NCT03364400 December 6, 2017.

Editorial acknowledgement

Legal entity responsible for the study

Vigeo Therapeutics, Inc.

Funding

Vigeo Therapeutics, Inc.

Disclosure

S. Wang: Shareholder / Stockholder / Stock options, Full / Part-time employment: Vigeo Therapeutics, Inc. K. Kerstein: Full / Part-time employment: Vigeo Therapeutics, Inc. G. Berk: Advisory / Consultancy: Vigeo Therapeutics, Inc. M.J. Cieslewicz: Leadership role, Shareholder / Stockholder / Stock options, Full / Part-time employment: Vigeo Therapeutics. J. Watnick: Leadership role, Shareholder / Stockholder / Stock options, Full / Part-time employment, Officer / Board of Directors: Vigeo Therapeutics, Inc. All other authors have declared no conflicts of interest.