Clinical Activity, Safety and Biomarkers of PD-L1 Blockade in Non-Small-Cell Lung Cancer (NSCLC): Additional Analysis From a Clinical Study of the Engineered Antibody MPDL3280A (anti PD-L1) J.C. Soria et al.
Background: Antitumor immune response may be inhibited by PD-L1 expression. MPDL3280A is a human monoclonal antibody that contains an engineered Fc-domain whose aim is to restore tumor specific T cell immunity by blocking PD-L1 from binding with its receptors.
Methods: This is a phase 1 expansion study in patients with squamous or non-squamous non-small cell lung cancer receiving MPDL3280A IV q. three-weekly. Patients were treated for up to one year. Objective response rate was assessed by RECIST. Cigarette smoking history was captured at baseline. IHC scores for PD-L1 expression were also assessed.
Results: There were 53 patients with NSCLC treated with this antibody. 76% had non-squamous cell carcinoma and 55% had multiple lines of previous treatment. The agent was noted to be well tolerated with no episodes of pneumonitis and no grade 3 to 5 episodes of diarrhea. The overall response rate was 23% with 21% in the non-squamous cell population and 27% in the squamous cell population. In addition, IHC scores for PD-L1 expression demonstrated increasing response rates with increasing IHC scores. The response rate for IHC 3 was 83% and 46% for IHC 2 and 3. The median time to response was 12 weeks with a median duration of response of 48 weeks. In addition, the response rates were noted to be increased in smokers although nonsmokers responded as well.