TRAIL receptor agonist TLY012 in combination with PD-1 inhibition promotes tumor regression in an immune-competent mouse model of pancreatic ductal adenocarcinoma.

Pancreatic ductal adenocarcinoma (PDAC) has an immunosuppressed, apoptosis-resistant phenotype. TLY012 is pegylated recombinant Tumor necrosis factor-Related Apoptosis-Inducing Ligand (TRAIL), an orphan drug for chronic pancreatitis and systemic sclerosis. Innate immune TRAIL signaling suppresses cancer.

Synergistic combination therapy with ONC201 or ONC206, and enzalutamide or darolutamide in preclinical studies of castration-resistant prostate cancer.

Androgen receptor (AR) signaling is a target in prostate cancer therapy and can be treated with non-steroidal anti-androgens (NSAA) including enzalutamide, and apalutamide for patients with advanced disease. Metastatic castration-resistant prostate cancer (mCPRC) develop resistance becomes refractory to therapy limiting patient overall survival. Darolutamide is a novel next-generation androgen receptor-signaling inhibitor that is FDA approved for non-metastatic castration resistant prostate cancer (nmCRPC).