Safety and clinical activity of durvalumab (MEDI4736), an anti-PD-L1 antibody, in treatment-naïve patients with advanced non‒small-cell lung cancer

There is an urgent need for improved first-line therapy for non–small-cell lung cancer (NSCLC) for which current molecularly targeted therapies is not indicated. The PD-1/PD-L1 axis is an important immune inhibitory pathway contributing to tumor cell escape from immunosurveillance. A phase 1/2 dose-escalation and dose-expansion study is ongoing to evaluate the safety and efficacy of durvalumab, a modified human immunoglobulin G1 monoclonal antibody that blocks PD-L1 binding to PD-1 and CD80, in patients with advanced NSCLC or other solid tumor types. In a study by Antonia and colleagues, durvalumab 10 mg/kg was given every 2 weeks for up to 12 months to treatment-naïve patients with histologically or cytologically documented Stage IIIB/IV squamous (SQ) or non-SQ NSCLC.¹Retreatment was permitted if disease progressed after 12 months of therapy. Response was investigator-assessed per RECIST v1.1, and the results were presented by histology and PD-L1 status. A total of 59 patients (48 PD-L1-high; 9 PD-L1-low; 58 EGFR wild type [WT]; 57 ALK WT; 55 KRAS WT; 29 SQ; 30 non-SQ) received a median of 8 doses (range, 1-27) of durvalumab. Drug-related adverse events (AEs) were reported in 59% of patients; the most frequent were fatigue (15%), diarrhea (12%), and decreased appetite (10%). Grade ≥3 drug-related AEs were reported in 9% of patients and led to discontinuation in 4 (7%) patients. At ≥12 weeks of follow-up, 52 patients (23 SQ; 29 non-SQ) were evaluable for response; overall response rate (ORR; confirmed complete response and partial response) was 27% (29% in PD-L1-high tumors and 11% in those with PD-L1-low or negative tumors), and the disease control rate was 42% (41% in PD-L1-high; 44% in PD-L1-low). ORR was similar for patients with SQ (28%) and non-SQ (27%) NSCLC. Responses are ongoing in 11 (69%) patients, with a duration of response ranging from 5.7+ to 70.1+ weeks. The authors concluded that durvalumab monotherapy has a manageable safety profile with early evidence of clinical benefit in treatment-naïve SQ or non-SQ advanced NSCLC. A development program of durvalumab alone and in combination with other agents is currently ongoing in advanced NSCLC.

1. Antonia SJ, et al. ASCO 2016. Abstract 9029.