Giraudet, Anne-Laure Centre Léon Bérard
Cassier, Philippe Alexandre Centre Léon Bérard
Iwao-Fukukawa, Chicaco OncoTherapy Science
Garin, Gwenaelle Centre Léon Bérard
Badel, Jean-Noël Centre Léon Bérard
Kryza, David Université Lyon 1|CNRS
Chabaud, Sylvie Centre Léon Bérard
Gilles-Afchain, Laurence Centre Léon Bérard
Clapisson, Gilles Centre Léon Bérard
Desuzinges, Claude Centre Léon Bérard
Sarrut, David Université Lyon 1|CNRS
Halty, Adrien Université Lyon 1|CNRS
Italiano, Antoine Institut Bergonié
Mori, Masaharu The University of Tokushima
Tsunoda, Takuya The University of Tokyo
Katagiri, Toyomasa The University of Tokyo Tokushima University Educator and Researcher Directory KAKEN Search Researchers
Nakamura, Yusuke The University of Tokyo|The University of Chicago
Alberti, Laurent CNRS
Cropet, Claire Centre Léon Bérard
Baconnier, Simon Centre Léon Bérard
Berge-Montamat, Sandrine Centre Léon Bérard
Pérol, David Centre Léon Bérard
Blay, Jean-Yves Centre Léon Bérard
Background: Synovial Sarcomas (SS) are rare tumors occurring predominantly in adolescent and young adults with a dismal prognosis in advanced phases. We report a first-in-human phase I of monoclonal antibody (OTSA-101) targeting FZD10, overexpressed in most SS but not present in normal tissues, labelled with radioisotopes and used as a molecular vehicle to specifically deliver radiation to FZD10 expressing SS lesions.
Methods: Patients with progressive advanced SS were included. In the first step of this trial, OTSA-101 in vivo biodistribution and lesions uptake were evaluated by repeated whole body planar and SPECT-CT scintigraphies from H1 till H144 after IV injection of 187 MBq of 111In-OTSA-101. A 2D dosimetry study also evaluated the liver absorbed dose when using 90Y-OTSA-101. In the second step, those patients with significant tumor uptake were randomized between 370 MBq (Arm A) and 1110 MBq (Arm B) of 90Y-OTSA-101 for radionuclide therapy.
Results: From January 2012 to June 2015, 20 pts. (median age 43 years [21–67]) with advanced SS were enrolled. Even though 111In-OTSA-101 liver uptake appeared to be intense, estimated absorbed liver dose was less than 20 Gy for each patient. Tracer intensity was greater than mediastinum in 10 patients consistent with sufficient tumor uptake to proceed to treatment with 90Y-OTSA-101: 8 were randomized (Arm A: 3 patients and Arm B: 5 patients) and 2 were not randomized due to worsening PS. The most common Grade ≥ 3 AEs were reversible hematological disorders, which were more frequent in Arm B. No objective response was observed. Best response was stable disease in 3/8 patients lasting up to 21 weeks for 1 patient.
Conclusions: Radioimmunotherapy targeting FZD10 is feasible in SS patients as all patients presented at least one lesion with 111In-OTSA-101 uptake. Tumor uptake was heterogeneous but sufficient to select 50% of pts. for 90Y-OTSA-101 treatment. The recommended activity for further clinical investigations is 1110 MBq of 90Y-OTSA-101. However, because of hematological toxicity, less energetic particle emitter radioisopotes such as Lutetium 177 may be a better option to wider the therapeutic index.
Trial registration: The study was registered on the NCT01469975 ( https://clinicaltrials.gov/ct2/show/NCT01469975 ) website with a registration code NCT01469975 on November the third, 2011.
BioMed Central|Springer Nature
© The Author(s). 2018 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
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Institute of Advanced Medical Sciences