The approval of checkpoint inhibitors that block the interaction between PD-L1 and programmed cell death protein 1, or PD-1, has shifted the treatment paradigm of numerous cancers, due to improved response rates and overall survival benefit.
These therapeutics, however, achieve a lasting benefit only for a minority of patients and numerous combination approaches have been tested clinically with the goal of further activating tumor reactive T-cells. One such approach is agonist antibodies targeting 4-1BB, a member of the TNFRSF that has been shown to provide co-stimulatory function to T-cells. While 4-1BB agonism has shown some clinical promise, the efficacy seen with this approach has been limited due to dose limiting toxicities that result from systemic activation of 4-1BB.
We believe INBRX-105 has the potential to provide PD-L1/PD-1 inhibition while simultaneously and selectively activating 4-1BB + T-cells in the tumor only, thus overcoming the toxicity issues that have limited prior 4-1BB agonists.