ARX517 + apalutamide

ARX517 + apalutamide is an investigational combination therapy for metastatic castration-resistant prostate cancer (mCRPC). ARX517 is a next-generation antibody-drug conjugate (ADC) consisting of a fully humanized anti–prostate-specific membrane antigen (PSMA) monoclonal antibody conjugated via site-specific, stable oxime chemistry to the microtubule inhibitor amberstatin-269 (AS269). The ADC delivers its cytotoxic payload specifically to PSMA-expressing prostate cancer cells upon internalization, causing cell death. ARX517 is designed to overcome the instability and toxicity limitations seen in earlier PSMA-targeted ADCs by using a noncleavable PEG linker and a precisely controlled drug-to-antibody ratio. Apalutamide is a small molecule nonsteroidal antiandrogen that inhibits androgen receptor (AR) signaling by binding directly to the androgen receptor and preventing its translocation, DNA binding, and activation. Combining ARX517 with apalutamide targets both the PSMA pathway and the androgen receptor pathway. This combination is under clinical investigation for improving treatment outcomes in patients with mCRPC who have progressed on prior therapies.