CTLA-4 was commercially validated as the first target to correct immune defects in cancer patients through antibody-based immunotherapy. However, CTLA-4-targeting drugs currently in clinical use or testing cause immunotherapy-related adverse events (irAE) in high percentages of cancer patients. Drs. Liu and Zheng, our co-founders, demonstrated that the cancer immunotherapeutic effect (CITE) and irAE are mediated by distinct mechanisms and thus can be uncoupled through engineering of antibodies with stronger CITE but minimal irAE.

ONC-392, a humanized IgG1 monoclonal antibody, with modified Fc, is such an antibody that targets CTLA-4 in a unique way to selectively eliminate tumor-infiltrating regulatory T cells (Treg) without affecting T cell activation in the peripheral T cells. Compared with other commercial and clinical stage anti-CTLA-4 antibodies, ONC-392 has more robust CITE but dramatically lower irAE in preclinical models. A Phase 1A/1B clinical trial is currently underway to assess the safety, pharmacokinetics, and efficacy of ONC-392 as a single agent in advanced solid tumors and in combination with anti-PD(L)1 standard of care in Non- Small Cell Lung Cancer (NSCLC) (PRESERVE-001, NCT04140526).

 

 

 

References

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