Research Papers:

Phase I clinical study of RG7356, an anti-CD44 humanized antibody, in patients with acute myeloid leukemia

Norbert Vey _, Jacques Delaunay, Giovanni Martinelli, Walter Fiedler, Emmanuel Raffoux, Thomas Prebet, Carlos Gomez-Roca, Cristina Papayannidis, Maxim Kebenko, Peter Paschka, Randolph Christen, Ernesto Guarin, Ann-Marie Bröske, Monika Baehner, Michael Brewster, Antje-Christine Walz, Francesca Michielin, Valeria Runza, Valerie Meresse and Christian Recher

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Oncotarget. 2016; 7:32532-32542. https://doi.org/10.18632/oncotarget.8687

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Norbert Vey1,2, Jacques Delaunay3, Giovanni Martinelli4, Walter Fiedler5, Emmanuel Raffoux6, Thomas Prebet1, Carlos Gomez-Roca7,8, Cristina Papayannidis4, Maxim Kebenko5, Peter Paschka9, Randolph Christen10, Ernesto Guarin11, Ann-Marie Bröske12, Monika Baehner12, Michael Brewster13, Antje-Christine Walz11, Francesca Michielin11, Valeria Runza12, Valerie Meresse11, Christian Recher7,14

1Institut Paoli-Calmettes, Marseille, France

2Aix Marseille Université, Marseille, France

3Service d'Hématologie Clinique, Hôpital Hôtel-Dieu, Nantes, France

4Department of Experimental, Diagnostic and Specialty Medicine, University of Bologna, Bologna, Italy

5Department of Medicine II, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

6Hôpital Saint Louis, AP-HP, EA3518 Université Paris VII, Paris, France

7Institut Universitaire du Cancer de Toulouse Oncopole, Toulouse, France

8Institut Claudius Regaud, Clinical Research Unit, Toulouse, France

9Department of Internal Medicine III, University Hospital Ulm, Ulm, Germany

10Product Development, Safety Risk Management, Roche, Basel, Switzerland

11Pharma Research & Early Development, Roche Innovation Center Basel, Basel, Switzerland

12Pharma Research & Early Development, Roche Innovation Center Penzberg, Penzberg, Germany

13Pharma Research & Early Development, Roche Innovation Centre, Welwyn, UK

14CHU de Toulouse, Université Toulouse III, Toulouse, France

Correspondence to:

Norbert Vey, email: [email protected]

Keywords: RG7356, relapsed/refractory acute myeloid leukemia, anti-CD44 humanized antibody, phase I trial, cell adhesion

Received: January 20, 2016     Accepted: March 28, 2016     Published: April 11, 2016


RG7356, a recombinant anti-CD44 immunoglobulin G1 humanized monoclonal antibody, inhibits cell adhesion and has been associated with macrophage activation in preclinical models. We report results of a phase I dose-escalation study of RG7356 in relapsed/refractory acute myeloid leukemia (AML).

Eligible patients with refractory AML, relapsed AML after induction chemotherapy, or previously untreated AML not eligible for intensive chemotherapy were enrolled and received intravenous RG7356 at dosages ≤ 2400 mg every other week or ≤ 1200 mg weekly or twice weekly; dose escalation started at 300 mg.

Forty-four patients (median age, 69 years) were enrolled. One dose-limiting toxicity occurred (grade 3 hemolysis exacerbation) after one 1200 mg dose (twice-weekly cohort). The majority of adverse events were mild/moderate. Infusion-related reactions occurred in 64% of patients mainly during cycle 1. Two patients experienced grade 3 drug-induced aseptic meningitis. Pharmacokinetics increased supraproportionally, suggesting a target-mediated drug disposition (TMDD) at ≥ 1200 mg. Two patients achieved complete response with incomplete platelet recovery or partial response, respectively. One patient had stable disease with hematologic improvement.

RG7356 was generally safe and well tolerated. Maximum tolerated dose was not reached, but saturation of TMDD was achieved. The recommended dose for future AML evaluations is 2400 mg every other week.

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