Abstract CT083: A pivotal randomized phase II study of anetumab ravtansine or vinorelbine in patients with advanced or metastatic pleural mesothelioma after progression on platinum/pemetrexed-based chemotherapy (NCT02610140)
Authors: Hassan Raffit , Nemunaitis John J. , van Meerbeeck Jan P. , Jennens Ross , Blumenschein George R. , Fennell Dean A. , Kindler Hedy L. , Novello Silvia , Elbi Cem , Walter Annette , Serpico Danila , Fountain Emma , Vingerhoedt Sandra , Brown Christine , Siegel Jonathan , Childs Barrett H. 
Published: July 2016

Abstract
Background: Mesothelioma is a rare but aggressive cancer with a 5-year survival rate less than 10%. Mesothelin is a protein normally present on mesothelial cells and overexpressed in the majority of mesotheliomas. Anetumab ravtansine (BAY 94-9343) is a novel fully human anti-mesothelin IgG1 antibody conjugated to ravtansine, an antitubulin cytotoxic agent. In a phase I study, anetumab ravtansine at 6.5 mg/kg on a q3w IV schedule was well tolerated and showed encouraging durable tumor responses in patients with previously treated mesothelioma.
Design: A randomized, open-label, active-controlled, 2-arm, multicenter, phase II trial to evaluate the efficacy and safety of anetumab ravtansine at 6.5 mg Q3W versus vinorelbine 30 mg/m2 QW in patients with advanced or metastatic malignant pleural mesothelioma overexpressing mesothelin and who have progressed on first-line platinum/pemetrexed-based chemotherapy.
Objectives: The primary objective is to test the superiority of anetumab ravtansine monotherapy over vinorelbine in progression-free survival (PFS). The secondary objectives of this study include overall survival, patient-reported outcomes (PRO), tumor response, and safety. Exploratory objectives include immunogenicity of anetumab ravtansine, pharmacokinetics, and biomarkers of response.
Methods: Biomarker sampling will be performed on all patients to measure tumor mesothelin expression levels at prescreening. Biomarker-positive patients with moderate (2+) and/or strong (3+) level in at least 30% of tumor cells will be randomized and start study treatment following progression after 1st line treatment of platinum/pemetrexed (with or without bevacizumab).
Approximately 183 patients meeting eligibility criteria will berandomized in a 2:1 ratio to receive anetumab ravtansine or vinorelbine. Randomization will be stratified by geographic region (Rest of World v. Asia) and time to progression on 1st line treatment (? 6 months vs &lt; 6 months). The primary endpoint, PFS per modified RECIST criteria for metastatic pleural mesothelioma per central review, will be tested using a log-rank test stratified by randomization strata, with 1-sided significance level 0.0125. The primary analysis will occur after approximately 117 PFS events. Assuming true median PFS of 3.6 months under vinorelbine treatment, the primary hypothesis test is designed to detect a 100% prolongation of true PFS (median 7.2 months) with 90% power. Novel study methods include a grading system for AEs of special interest and the PRO instrument.
Results: This trial is open and currently accruing patients.
Citation Format: Raffit Hassan, John J. Nemunaitis, Jan P. van Meerbeeck, Ross Jennens, George R. Blumenschein, Jr, Dean A. Fennell, Hedy L. Kindler, Silvia Novello, Cem Elbi, Annette Walter, Danila Serpico, Emma Fountain, Sandra Vingerhoedt, Christine Brown, Jonathan Siegel, Barrett H. Childs. A pivotal randomized phase II study of anetumab ravtansine or vinorelbine in patients with advanced or metastatic pleural mesothelioma after progression on platinum/pemetrexed-based chemotherapy (NCT02610140). [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr CT083.