Avelumab (MSB0010718C), an anti-PD-L1 antibody, in advanced NSCLC patients: A phase 1b, open-label expansion trial in patients progressing after platinum-based chemotherapy.

8034 Background: The programmed death-1 receptor (PD-1) and its ligand (PD-L1) are key therapeutic targets in the reactivation of the immune response against cancer. Avelumab* (MSB0010718C) is a fully human anti-PD-L1 IgG1 antibody being investigated in clinical trials. We report safety and clinical activity in patients (pts) with advanced NSCLC progressing after platinum-based chemotherapy (NCT01772004). Methods: Pts were treated with avelumab at 10 mg/kg Q2W until progression, confirmed complete response (CR), or toxicity. A prespecified analysis of 184 pts with ≥ 3 months follow-up (range 3-13) was performed. Tumors were assessed every 6 weeks (w) (RECIST 1.1) and unconfirmed best overall response (BOR) was evaluated. Tumor PD-L1 expression was assessed by immunohistochemistry. Results: Median age was 65y (range 31-83) and ECOG PS was 0 (30%) or 1 (70%). Histology was adenocarcinoma (62%), squamous cell carcinoma (29%), or other (9%). Any grade drug-related treatment-emergent adverse events (TEAEs) occurred in 139 (75.5%) pts; the most common ( > 5%) were fatigue, nausea, infusion-related reactions (IRRs), chills, decreased appetite, and diarrhea. Drug-related grade ≥ 3 TEAEs occurred in 22 (12%) pts, including 4 IRRs. Drug-related deaths were reported (n = 3; radiation pneumonitis, acute respiratory failure, and disease progression). Objective responses (OR) were observed in 22 (12%) pts (95% CI: 7.6, 17.5; 1 CR, 21 partial responses; 18 were ongoing at data cutoff). BOR of stable disease was observed in 70 pts (38%). Median progression-free survival (PFS) was 11.6 w (95% CI: 8.4, 12.1) and the PFS rate at 24 w was 25.4% (95% CI: 18.3, 33.2). Tumors were PD-L1(+) in 86% of evaluable pts (1% cutoff). The ORR in PD-L1(+) pts (n = 118) was 14.4% and 10.0% in PD-L1(-) pts (n = 20). Median PFS in PD-L1(+) pts was 11.7 w vs 5.9 w in PD-L1(-) pts. Conclusions: In pts with previously treated NSCLC, avelumab was administered safely with a toxicity profile similar to other anti-PD-1/anti-PD-L1 agents. A trend of greater activity in pts with PD-L1(+) tumors was observed. A randomized phase 3 trial of avelumab in pts with advanced NSCLC is planned. *Proposed INN. Clinical trial information: NCT01772004.