ONCT-534 is a potentially first-in-class dual-action androgen receptor inhibitor (DAARI) small molecule, currently in preclinical development. ONCT-534 is designed to be a next-generation treatment option for patients with advanced prostate cancer, including the emerging unmet medical need of androgen receptor splice variant (AR-SV)-expressing tumors. It was originally discovered at the Center for Cancer Research of the University of Tennessee Health Science Center.


Tumor-resistance mechanisms related to the expression of androgen receptor splice variants (AR-SV), such as AR-V7, represent an important unmet need for prostate cancer patients. Current standard of care treatment options such as enzalutamide or apalutamide only bind to the Ligand-Binding Domain (LBD) of the androgen receptor, which may explain their reduced efficacy in patients with AR-SV-expressing tumors, as these AR variants lack the LBD.

ONCT-534 has a novel and unique mechanism of action, as it interacts with both the N-terminal Domain (NTD) and the Ligand-Binding Domain (LBD) of the androgen receptor (AR), inhibiting its function and leading to AR protein degradation. We believe that this NTD binding is relevant to the activity of ONCT-534 against tumors expressing AR splice-variants.

We are enrolling patients:

  • With relapsed/refractory mantle cell lymphoma (MCL) for a Phase 1b/2 study of zilovertamab in combination with ibrutinib
  • With chronic lymphocytic leukemia (CLL) for a Phase 2 clinical study of zilovertamab in combination with venetoclax, a Bcl-2 inhibitor 
  • With Ewing sarcoma for a Phase 1 study of ONCT-216, our small-molecule inhibitor of ETS-family transcription factor oncoproteins, in combination with vincristine
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