CGX1321

Wnt/β-catenin pathway modulation increases MHC I expression and promotes tumor leukocytic infiltration, facilitating a pro-immune TME associated with decreased tumor burden. This intervention overcomes common tumor immune-evasion mechanisms and may render ovarian tumors susceptible to immunotherapy.

P1b, N=72, Recruiting, Curegenix Inc. | Trial completion date: Dec 2022 --> Mar 2023 | Trial primary completion date: Dec 2022 --> Mar 2023

CGX-1321 significantly reduced tumor burden and enhanced CD8+ T cell levels in ovarian cancer, nevertheless the addition of DKN-01 or anti-PD-1 therapies did not enhance these effects of CGX-1321. Further investigation is needed to determine if CGX-1321 + DKN-01 combination treatment sensitizes pre-clinical ovarian cancer to ICB therapy.

CGX-1321 decreased omental weight and ascites volume, while DKN-01 increased the cellular percentage of NK cells. Both DKN-01 and CGX-1321 increased CD8+ T cells. Wnt-inhibition is therapeutically promising in EOC, and the combination of a PORCN inhibitor with DKN-01 could improve the response to immune checkpoint blockage and further investigation is warranted.

When CD8 T cells were depleted, CGX1321 treatment did not have the same magnitude of effect on tumor growth. Our investigation confirmed an increase in Wnt activity correlated with a decreased T-cell-inflamed environment; a relationship that was further supported in our pre-clinical model that suggests inhibiting the Wnt/β-catenin pathway was associated with decreased tumor growth and improved survival via a partial dependence on CD8 T cells.

CGX1321 treatment inhibited tumor growth in ID8p53-/--luciferase tagged tumors; this was not seen in ID8p53-/-nonluciferase-tagged mice. Immune changes in the TME were not significant in this model, but were not measured in the luciferase-tagged model. There was no difference in tumor burden in ID8p53-/- injected DC-intrinsic β-catenin absent model.

CGX1321 treatment inhibited tumor growth in ID8p53-/--luciferase tagged tumors; this was not seen in ID8p53-/-nonluciferase-tagged mice. Immune changes in the TME were not significant in this model, but were not measured in the luciferase-tagged model. There was no difference in tumor burden in ID8p53-/- injected DC-intrinsic β-catenin absent model.

CGX1321 treatment inhibited tumor growth in ID8p53-/--luciferase tagged tumors; this was not seen in ID8p53-/-nonluciferase-tagged mice. Immune changes in the TME were not significant in this model, but were not measured in the luciferase-tagged model. There was no difference in tumor burden in ID8p53-/- injected DC-intrinsic β-catenin absent model.

CGX1321 treatment inhibited tumor growth in ID8p53-/--luciferase tagged tumors; this was not seen in ID8p53-/-nonluciferase-tagged mice. Immune changes in the TME were not significant in this model, but were not measured in the luciferase-tagged model. There was no difference in tumor burden in ID8p53-/- injected DC-intrinsic β-catenin absent model.