Avelumab (MSB0010718C; anti-PD-LI) vs platinum-based doublet as first-line treatment for metastatic or recurrent PDL1-positive non-small-cell lung cancer: The phase 3 JAVELIN Lung 100 trial

Background: Programmed death‐1 receptor ligand (PD‐L1) is a key therapeutic target in the reactivation of the immune response against multiple cancers. Avelumab∗ is a fully human anti‐PD‐L1 IgG1 antibody that has shown promising efficacy and an acceptable safety profile in multiple tumor types, including non‐small‐cell lung cancer (NSCLC). This open‐label phase 3 trial (NCT02576574 ) compares single‐agent avelumab vs platinumbased doublet chemotherapy as first‐line treatment for patients (pts) with PD‐L1‐positive (+) recurrent or stage IV NSCLC negative for activating EGFR mutation and ALK translocation. Methods: The primary objective of this global, multicenter, randomized trial is to demonstrate superiority of avelumab in improving progression‐free survival (PFS) according to RECIST 1.1 and as assessed by an Independent Review Committee (IRC) vs platinum‐based doublet chemotherapy. Approximately 420 pts with PD‐L1+ tumors, as determined by companion diagnostic assay, will be randomized. Eligibility criteria include: histologically confirmed metastatic or recurrent NSCLC, ECOG PS 0‐1, no prior systemic treatment for recurrent/metastatic NSCLC, no prior therapy with any drug targeting T cell coregulatory proteins, no concurrent anticancer treatment or immunosuppressive agents, and known EGFR mutation/ALK translocation‐negative tumor. Pts receive either avelumab 10 mg/kg as a 1h intravenous (IV) infusion Q2W or a platinum‐based doublet (nonsquamous histology: pemetrexed 500 mg/m2 + cisplatin 75 mg/m2 or carboplatin AUC 6; squamous histology: paclitaxel 200 mg/m2 + carboplatin AUC 6, gemcitabine 1250 mg/m2 + cisplatin 75 mg/m2 , or gemcitabine 1000 mg/m2 + carboplatin AUC 5) by IV infusion. Treatment is given until disease progression, unacceptable toxicity, or consent withdrawal, with a maximum of 6 cycles of chemotherapy. Secondary endpoints include objective response rate, overall survival, quality of life (assessed via EQ‐5D, EORTC QLQ‐C30, and EORTC QLQ‐LC13), safety as per NCI‐CTCAE v4.03, and tumor biomarkers. Trial enrollment began in Oct 2015.