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392 Phase 1 study of CI-8993 anti-VISTA antibody in patients with advanced solid tumor malignancies
  1. Elizabeth Martinez1,
  2. Jason Faris2,
  3. Reinhard Von Roemeling3,
  4. Steven Angelides3 and
  5. Melissa Johnson4
  1. 1Curis Inc, Durham, NC, USA
  2. 2Dartmouth-Hitchcock, Norris Cotton Cance, Lebanon, NH, USA
  3. 3Curis, Ridgefield, CT, USA
  4. 4Tennessee Oncology, Nashville, TN, USA


Background VISTA (V-domain Ig suppressor of T cell activation) is a key negative immune checkpoint regulator, locking T cells in a quiescent state, unlike PD1 and CTLA4, which are expressed on activated T cells. Preclinically, VISTA monoclonal antibody treatment increased the number of tumor-specific T cells in the periphery, and enhanced the infiltration, proliferation and effector function of tumor-reactive T cells within the tumor microenvironment (TME). VISTA blockade alters the suppressive feature of the TME by decreasing the presence of monocytic myeloid-derived suppressor cells and increasing the presence of activated dendritic cells (DCs) within the TME leading to enhanced T cell mediated immunity. VISTA monoclonal antibody administration as a monotherapy has been shown to suppress the growth of both transplantable and inducible melanoma in preclinical models. CI-8993 is a first-in-class, fully human immunoglobulin (Ig) G1κ monoclonal antibody (mAb) against the VISTA ligand. Prior human clinical evaluation of CI-8993 demonstrated target-related clinical findings and pharmacodynamic activity at 0.15 mg/kg.

Methods This phase 1 study is being conducted in the USA (NCT04475523) and is designed as a 3+3 dose escalation study beginning at 0.15 mg/kg. Patients with solid tumor malignancy (non-lymphoma) that is metastatic or unresectable and considered relapsed and/or refractory to prior therapy will be included, excluding prior CAR-T therapy or allogenic transplant. Patients will be treated with an initial step-dose of CI-8993 by IV infusion, followed by every 2 weeks of a full dose, until disease progression or toxicity. Efficacy, pharmacokinetics, pharmacodynamic and safety endpoints will be monitored and reported.

Results N/A

Conclusions N/A

Ethics Approval The study was approved by Dartmouth-Hitchcock, Norris Cotton Cancer Center Ethics Board, approval number IRB00012031The study was approved Sarah Cannon Caner Research Institute, approval number IORG0000689

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