Clinical trials of MPDL3280A (anti-PDL1) in patients (pts) with non-small cell lung cancer (NSCLC).

TPS8123 Background: Blocking the PD-L1/PD-1 immune inhibitory signals can reinvigorate preexisting anticancer immunity and can lead to durable responses in NSCLC. MPDL3280A is a human anti-PD-L1 monoclonal antibody that contains an engineered Fc-domain. MPDL3280A targets PD-L1, preventing binding to its receptors PD-1 and B7.1, thus restoring tumor-specific T-cell immunity. MPDL3280A does not disrupt the PD-L2/PD-1 interaction, which is potentially implicated in autoimmune lung toxicity. In a Phase I study, MPDL3280A led to antitumor responses, with an overall response rate (ORR) of 23% (12/53) in previously-treated NSCLC pts, 46% (6/13) in those pts with a PD-L1 IHC score of 2 or 3 and 83% (5/6) in those pts with a PD-L1 IHC score of 3. Based on these results, we initiated a clinical program examining unselected and PD-L1-positive pts with locally advanced or metastatic NSCLC. Here, we describe the BIRCH and OAK trials. Methods: Both studies require pts aged ≥ 18 y with an ECOG status of 0 or 1 and measu...