First-in-human phase I clinical trial of RG7356, an anti-CD44 humanized antibody, in patients with advanced, CD44-expressing solid tumors

// C. Willemien Menke-van der Houven van Oordt 1 , Carlos Gomez-Roca 2 , Carla van Herpen 3 , Andrew L. Coveler 4 , Devalingam Mahalingam 5 , Henk M. W. Verheul 1 , Winette T. A. van der Graaf 3 , Randolph Christen 6 , Dominik Ruttinger 7 , Stefan Weigand 7 , Michael A. Cannarile 7 , Florian Heil 7 , Michael Brewster 8 , Antje-Christine Walz 9 , Tapan K. Nayak 9 , Ernesto Guarin 9 , Valerie Meresse 9 and Christophe Le Tourneau 10 1 Department of Medical Oncology, VU University Medical Center, Amsterdam, The Netherlands 2 Clinical Research Unit, Department of Medical Oncology, Institut Claudius Regaud, Institut Universitaire du Cancer de Toulouse – Oncopole, Toulouse, France 3 Radboud University Medical Center, Nijmegen, The Netherlands 4 Department of Medicine, Division of Oncology, University of Washington, Seattle, WA, USA 5 Cancer Therapy and Research Center, University of Texas Health Science Center, San Antonio, TX, USA 6 Product Development, Safety Risk Management, Roche, Basel, Switzerland 7 Pharma Research & Early Development, Roche Innovation Center, Penzberg, Germany 8 Pharma Research & Early Development, Roche Innovation Centre, Welwyn, UK 9 Pharma Research & Early Development, Roche Innovation Center Basel, Basel, Switzerland 10 Department of Medical Oncology, Institut Curie, Saint-Cloud & Paris, France, and Versailles-Saint-Quentin-en-Yvelines University, Versailles, France Correspondence to: C. Willemien Menke-van der Houven van Oordt, email: // Keywords : RG7356, anti-CD44 humanized antibody, advanced solid tumors, advanced CD44-expressing solid malignancies, phase I trial Received : March 28, 2016 Accepted : July 10, 2016 Published : August 05, 2016 Abstract Transmembrane glycoprotein CD44 is overexpressed in various malignancies. Interactions between CD44 and hyaluronic acid are associated with poor prognosis, making CD44 an attractive therapeutic target. We report results from a first-in-human phase I trial of RG7356, a recombinant anti-CD44 immunoglobulin G1 humanized monoclonal antibody, in patients with advanced CD44-expressing solid malignancies. Sixty-five heavily pretreated patients not amenable to standard therapy were enrolled and received RG7356 intravenously biweekly (q2w) or weekly (qw) in escalating doses from 100 mg to 2,250 mg. RG7356 was well tolerated. Most frequent adverse events were fever, headache and fatigue. Dose-limiting toxicities included headache (1,500 mg q2w and 1,350 mg qw) and febrile neutropenia (2,250 mg q2w). The maximum tolerated dose with q2w dosing was 1,500 mg, but was not defined for qw dosing due to early study termination. Clinical efficacy was modest; 13/61 patients (21%) experienced disease stabilization lasting a median of 12 (range, 6–35) weeks. No apparent dose- or dose schedule-dependent changes in biological activity were reported from blood or tissue analyses. Tumor-targeting by positron emission tomography (PET) using 89 Zr-labeled RG7356 was observed for doses ≥200 mg (q2w) warranting further investigation of this agent in combination regimens.