SYNFRIZZ: A first-in-human (FIH) study of a radiolabeled monoclonal antibody (Mab) targeting frizzled homolog 10 (FZD10) in patients (pts) with advanced synovial sarcomas (SyS)
| العنوان: | SYNFRIZZ: A first-in-human (FIH) study of a radiolabeled monoclonal antibody (Mab) targeting frizzled homolog 10 (FZD10) in patients (pts) with advanced synovial sarcomas (SyS) |
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| المؤلفون: | David Sarrut, Jean-Yves Blay, Anne Laure Giraudet, Laurence Gilles-Afchain, Jean-Noël Badel, David Pérol, Claire Cropet, Antoine Italiano, Sylvie Chabaud, Nicolas Penel, Takuya Tsunoda, Adrien Halty, Philippe A. Cassier, David Kryza, Simon J Baconnier, Yusuke Nakamura, Gwenaelle Garin, Toyomasa Katagiri, Masaharu Mori, Chicaco Iwao-Fukukawa |
| المصدر: | Journal of Clinical Oncology. 35:11054-11054 |
| بيانات النشر: | American Society of Clinical Oncology (ASCO), 2017. |
| سنة النشر: | 2017 |
| مصطلحات موضوعية: | 0301 basic medicine, Cancer Research, Frizzled, medicine.drug_class, business.industry, First in human, Monoclonal antibody, 03 medical and health sciences, 030104 developmental biology, 0302 clinical medicine, Oncology, 030220 oncology & carcinogenesis, medicine, Cancer research, In patient, business |
| الوصف: | 11054 Background: Advanced SyS are rare tumors with limited curative options. FZD10 is highly expressed in SyS but not in normal adult tissue. OTSA101 is a MAb targeting FZD10, labelled with a radioisotope. Methods: We conducted a phase I, FIH study including adult pts with advanced, refractory SyS. In part 1, pts received OTSA101 labelled with In111 used as radiotracer to assess biodistribution and tumor uptake. In part 2, pts with significant tumor uptake were randomized to receive OTSA101 labelled with 370MBq of Y90 (Arm A) or 1110MBq Y90 (Arm B). Primary endpoints were occurrence of unacceptable biodistribution /lack of tumor uptake in part 1 and occurrence of related adverse events (AEs) Grade ≥ 3 during the first 8 weeks following injection of Y90OTSA101 in part 2. Responses were assessed per RECIST 1.1. Results: From January 2012 to June 2015, 20 pts (10 females, median age 43, range 21-67) with advanced SyS were enrolled. Ten pts (50%) had sufficient tumor uptake to proceed to part 2 and 8 were randomized (Arm A: 3 and Arm B: 5). Two pts were not randomized due to worsening PS. During part 2, the most common Grade ≥ 3 AEs were haematological, including reversible lymphopenia, thrombocytopenia and neutropenia, and were more common in Arm B. One pt with SD after 12 weeks received a 2nd injection of 90Y-OTSA101, but experienced fatal hemoptysis. No objective response was observed. Best response was SD in 5/8 pts lasting up to 21 weeks for 1 pt. Conclusions: This FIH shows that radioimmunotherapy targeting FZD10 is feasible and safe in SyS pts. Tumor uptake was heterogeneous but sufficient to select 50% of pts for 90Y-OTSA101 treatment. Due to limited sample size, further clinical investigations are needed to assess the therapeutic activity of 90Y-OTSA101 with a recommended dose of 1110MBq of 90Y. Clinical trial information: NCT01469975. |
| تدمد: | 1527-7755 0732-183X 0146-9975 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_________::deb66c3a9cc4979043847f9cff928112Test https://doi.org/10.1200/jco.2017.35.15_suppl.11054Test |
| رقم الانضمام: | edsair.doi...........deb66c3a9cc4979043847f9cff928112 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15277755 0732183X 01469975 |
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