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*, Carlos Gomez-Roca, Carla van Herpen, Andrew L. Coveler, Devalingam Mahalingam, Henk M W Verheul, Winette T A van der Graaf, Randolph Christen, Dominik Rüttinger, Stefan Weigand, Michael A. Cannarile, Florian Heil, Michael Brewster, Antje Christine Walz, Tapan K. Nayak, Ernesto Guarin, Valerie Meresse, Christophe Le Tourneau

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

74 Scopus citations


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 89Zr-labeled RG7356 was observed for doses≥200 mg (q2w) warranting further investigation of this agent in combination regimens.

Original languageEnglish (US)
Pages (from-to)80046-80058
Number of pages13
Issue number48
StatePublished - 2016


  • Advanced CD44-expressing solid malignancies
  • Advanced solid tumors
  • Anti-CD44 humanized antibody
  • Phase I trial
  • RG7356

ASJC Scopus subject areas

  • Oncology


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