Avelumab is a fully human anti–PD-L1 immunoglobulin G1 antibody that binds PD-L1 and inhibits PD-1/PD-L1 interactions, but leaves the PD-1/PD-L2 pathway intact. This agent is under clinical investigation in multiple cancers.1 Verschraegen and colleagues reported on the safety and clinical activity of avelumab as first-line therapy in patients with non–small-cell lung cancer (NSCLC) from the JAVELIN phase 1b trial.2 Patients with advanced NSCLC not previously treated systemically for metastatic or recurrent disease, without an activatingEGFR mutation or ALK rearrangement, and not selected for PD-L1 expression, were treated with avelumab 10 mg/kg intravenously every 2 weeks until progression, unacceptable toxicity, or withdrawal. Responses were evaluated every 6 weeks by RECIST v1.1 criteria. PD-L1 expression was assessed by immunohistochemistry. A total of 145 patients received avelumab (median, 10 weeks [range, 2-30]) and were followed for a median duration of 13 weeks (range, 0-31). The patients’ NSCLC histology was adenocarcinoma (63.4%), squamous (26.9%), bronchoalveolar, large cell or other (3.5%), or unknown (6.2%). Treatment-related adverse events (TRAEs) occurred in 82 (56.6%; all grades) patients; those occurring ≥10% were infusion-related reaction (IRR; 16.6%) and fatigue (14.5%). Grade ≥3 TRAEs were reported in 13 (9.0%) patients; only IRR and fatigue occurred in >1 patient (each 2.1%). There were no treatment-related deaths.
Among 75 patients with ≥3 months of follow-up, unconfirmed overall response rate (ORR) was 18.7% (95% confidence interval [CI], 10.6-29.3), with 1 complete response, 13 partial responses, and 34 with stable disease. The disease control rate was 64%. PD-L1 expression was evaluable in 45 (60%) of 75 patients; based on a ≥1% cutoff for tumor cell staining, 77.8% of the patients were PD-L1+, and ORR was 20% in PD-L1+ patients versus 0% in PD-L1–negative patients. Median progression-free survival was 11.6 weeks (95% CI, 6.7-17.9) in PD-L1+ patients and 6.0 weeks (95% CI, 3.3-6.1) in PD-L1- patients. The authors concluded that single-agent avelumab showed an acceptable safety profile and clinical activity in patients with NSCLC who were EGFR-wildtype and ALK-negative, had not been previously treated for advanced disease, and were unselected for PD-L1 expression. A trend of higher ORR in PD-L1–positive tumors was suggested. Phase 3 trials of avelumab in NSCLC are currently ongoing to compare avelumab versus standard of care as first-line treatment of patients with NSCLC3 and to compare avelumab versus docetaxel in patients with NSCLC post-platinum doublet chemotherapy.4
