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ARV-393 + glofitamab

Development stage: Phase 1
Lead developer: Arvinas
Modality: PROTACs (E3 ligase recruitment) → Targeted Protein Degraders (TPDs) → Small Molecules, T-cell Engagers → Multispecific Antibodies → Engineered Antibody Formats → Antibody-Based Therapeutics, Bispecific Antibodies → Multispecific Antibodies → Engineered Antibody Formats → Antibody-Based Therapeutics, Bivalent/Multivalent Binders → Multivalent & Scaffold-Based Small Molecules → Small Molecules
Administration: Intravenous, Oral

Overview

ARV-393 + glofitamab is an investigational, chemotherapy-free combination regimen consisting of ARV-393, an oral proteolysis-targeting chimera (PROTAC) B-cell lymphoma 6 (BCL6) degrader, and glofitamab, a CD20×CD3 T-cell-engaging bispecific monoclonal antibody. ARV-393 binds to BCL6 and the E3 ubiquitin ligase cereblon, inducing the ubiquitination and subsequent proteasomal degradation of BCL6. This degradation upregulates CD20 expression and antigen presentation pathways on B-cell lymphoma cells. Glofitamab simultaneously binds CD20 on B cells and CD3 on T cells, recruiting and activating T cells to eliminate the lymphoma cells. Preclinical studies in humanized high-grade B-cell lymphoma models have demonstrated synergistic antitumor activity, resulting in deeper tumor growth inhibition and increased tumor regressions compared to either monotherapy. The combination is currently being evaluated in a Phase 1 clinical trial (NCT06393738) for adults with relapsed/refractory diffuse large B-cell lymphoma (DLBCL).

Other names: ARV-393 and glofitamabARV393 and glofitamabARV 393 and glofitamabARV-393 plus glofitamabARV393 plus glofitamabARV 393 plus glofitamabglofitamab + ARV-393

Targets

BCL6 (B cell lymphoma 6 protein)CD20 (B-lymphocyte antigen CD20)CD3 (T-cell surface glycoprotein CD3)26S proteasomeCRBN (Cereblon)

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