Durvalumab is a checkpoint inhibitor immunotherapy agent -- a human immunoglobulin monoclonal antibody (mAb). It is a human immunoglobulin G1 kappa (IgG1κ) monoclonal antibody that blocks the interaction of programmed cell death ligand 1 (PD-L1) with the PD-1 and CD80 (B7.1) molecules. Durvalumab is approved for treating patients with locally advanced or metastatic urothelial carcinoma under certain conditions. Olaparib is a Poly(ADP-ribose) polymerase (PARP) Inhibitor.
Olaparib is a PARP inhibitor, inhibiting poly(ADP-ribose) polymerase (PARP), an enzyme involved in DNA repair. It acts against cancers in people with hereditary BRCA1 or BRCA2 mutations, which include some ovarian, breast, and prostate cancers. It is approved for germline BRCA mutated (gBRCAm) advanced ovarian cancer that has received three or more prior lines of chemotherapy. Olaparib is the first PARP inhibitor to be approved by the FDA for gBRCAm metastatic breast cancer.
Results from I-SPY2 and preliminary results from two other ongoing Phase I/II trials suggest acceptable safety, as well as substantial synergy between anti-PD1/anti-PD-L1 agents and chemotherapy in the neoadjuvant treatment setting of early stage breast cancer. We hypothesize that the triple combination pf durvalumab, olaparib and taxol offer increased benefit, as impairment of DNA repair in proliferating cells should lead to increased mutational burden and higher neoantigen load, two important determinants of response to immune checkpoint inhibition.