Efficacy and safety of first-line avelumab in patients with advanced non-small cell lung cancer: results from a phase Ib cohort of the JAVELIN Solid Tumor study.

Avelumab, an antiprogrammed death ligand-1 antibody, is approved as a monotherapy for treatment of metastatic Merkel cell carcinoma and advanced urothelial carcinoma, and in combination with axitinib for advanced renal cell carcinoma. We report the efficacy and safety of first-line avelumab in advanced non-small cell lung cancer (NSCLC). In a phase I expansion cohort of the JAVELIN Solid Tumor trial, patients with treatment-naive, metastatic, or recurrent NSCLC received 10 mg/kg avelumab intravenously every 2 weeks. Endpoints included best overall response, duration of response (DOR), progression-free survival (PFS), overall survival (OS), and safety. Overall, 156 patients were enrolled and treated. Median duration of follow-up was 18.6 months (range, 15 to 23 months). The objective response rate was 19.9% (95% CI, 13.9 to 27.0), including complete response in 3 (1.9%) and partial response in 28 (17.9%). Median DOR was 12.0 months (95% CI, 6.9 to not estimable). Median PFS was 4.0 months (95% CI, 2.7 to 5.4) and the 6-month PFS rate was 38.5% (95% CI, 30.7 to 46.3). Median OS was 14.1 months (95% CI, 11.3 to 16.9) and the 12-month OS rate was 56.6% (95% CI, 48.2 to 64.1). Treatment-related adverse events (TRAEs) occurred in 107 patients (68.6%), including grade ≥3 TRAEs in 19 (12.2%). Immune-related adverse events and infusion-related reactions occurred in 31 (19.9%) and 40 patients (25.6%), respectively. No treatment-related deaths occurred. Avelumab showed antitumor activity with a tolerable safety profile as a first-line treatment in patients with advanced NSCLC. These data support further investigation of avelumab in the phase III JAVELIN Lung 100 study. ClinicalTrials.gov NCT01772004; registered January 21, 2013.

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Competing interests: CFV, EFM, NI, and FLC have nothing to disclose. GJ has received research funding from Merck KGaA, Novartis, Pfizer, and Roche; personal fees from AbbVie, Amgen, AstraZeneca, Bristol-Myers Squibb, Daiichi Sankyo, Eli Lilly, Novartis, Pfizer, and Roche; and non-financial support from Amgen, AstraZeneca, Bristol Myers Squibb, Eli Lilly, MedImmune, Merck KGaA, Novartis, Pfizer, and Roche. CHR owns stock in Pfizer. JB has provided advisory and speaker services for AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, Merck & Co, Roche, and Servier. KK has received research grants from EMD Serono (a business of Merck KGaA, Darmstadt, Germany) and Merck & Co; has served on advisory boards for EMD Serono and Merck & Co; and has received a honorarium from Merck & Co. JM has received research funding from Merck KGaA; research funding from Amgen, AstraZeneca, Bristol Myers Squibb, EMD Serono (a business of Merck KGaA, Darmstadt, Germany), Incyte, MacroGenics, Merck KGaA, Polynoma LLC, and Sanofi. JCM has provided speaker services for Boehringer Ingelheim and Merck KGaA, and has received travel expenses from Amgen, Eisai, Merck KGaA, and VentiRx Pharmaceuticals. MT has provided advisory and speaker services for Bristol Myers Squibb and Eisai; and advisory services for Array BioPharma, ArQule, Bayer, Blueprint Medicines, Loxo Oncology, Novartis, and Sanofi Genzyme. DS has provided consultancy or advisory services and received research funding from AbbVie, Amgen, AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Eli Lilly, Foundation Medicine, GlaxoSmithKline, Merck KGaA, Nektar, Novartis, Pfizer, Roche/Genentech, and Takeda Oncology; received travel expenses from AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Eli Lilly, EMD Serono (a business of Merck KGaA, Darmstadt, Germany), Intuitive Surgical, Merck KGaA, Perdue Pharma, Pfizer, Roche/Genentech, Sanofi Genzyme, Spectrum Pharmaceuticals, and Sysmex; provided consultancy or advisory services for Aptitude Health, Evelo Biosciences, Illumina, Moderna, Pharma Mar, and Precision Oncology; and received research funding from Acerta Pharma, Aeglea Biotherapeutics, ARMO BioSciences, Astellas Pharma, Celldex Therapeutics, Clovis Oncology, Daiichi Sankyo, EMD Serono (a business of Merck KGaA, Darmstadt, Germany), G1 Therapeutics, GRAIL, Ipsen, Neon Therapeutics, Oncogenex Pharmaceuticals, Takeda Oncology, Tesaro, and Transgene, and the University of Texas Southwestern Medical Center—Simmons Cancer Center. DW has provided advisory services for and received travel expenses from Merck KGaA. HJG is an employee of Merck KGaA, Darmstadt, Germany. DZ is an employee of Merck Serono Pharmaceutical R&D Co, Beijing, China; a business of Merck KGaA, Darmstadt, Germany. NM and MB are employees of EMD Serono, Inc; a business of Merck KGaA, Darmstadt, Germany. JLG has received research funding from EMD Serono, Inc (a business of Merck KGaA, Darmstadt, Germany).