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Phase 1/2 study evaluating the safety and efficacy of DSP‐7888 dosing emulsion in myelodysplastic syndromes
DSP‐7888 is an immunotherapeutic cancer vaccine derived from the Wilms’ tumor gene 1 (WT1) protein. This phase 1/2 open‐label study evaluated the safety and efficacy of DSP‐7888 dosing emulsion in patients with myelodysplastic syndromes (MDS). DSP‐7888 was administered intradermally (3.5 or 10.5 mg)...
Autores principales: | , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8990724/ https://www.ncbi.nlm.nih.gov/pubmed/34932235 http://dx.doi.org/10.1111/cas.15245 |
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author | Ueda, Yasunori Usuki, Kensuke Fujita, Jiro Matsumura, Itaru Aotsuka, Nobuyuki Sekiguchi, Naohiro Nakazato, Tomonori Iwasaki, Hiromi Takahara‐Matsubara, Mariko Sugimoto, Saori Goto, Masashi Naoe, Tomoki Kizaki, Masahiro Miyazaki, Yasushi Aakashi, Koichi |
author_facet | Ueda, Yasunori Usuki, Kensuke Fujita, Jiro Matsumura, Itaru Aotsuka, Nobuyuki Sekiguchi, Naohiro Nakazato, Tomonori Iwasaki, Hiromi Takahara‐Matsubara, Mariko Sugimoto, Saori Goto, Masashi Naoe, Tomoki Kizaki, Masahiro Miyazaki, Yasushi Aakashi, Koichi |
author_sort | Ueda, Yasunori |
collection | PubMed |
description | DSP‐7888 is an immunotherapeutic cancer vaccine derived from the Wilms’ tumor gene 1 (WT1) protein. This phase 1/2 open‐label study evaluated the safety and efficacy of DSP‐7888 dosing emulsion in patients with myelodysplastic syndromes (MDS). DSP‐7888 was administered intradermally (3.5 or 10.5 mg) every 2 weeks for 6 months and then every 2‐4 weeks until lack of benefit. Twelve patients were treated in phase 1 (3.5 mg, n = 6; 10.5 mg, n = 6), with no dose‐limiting toxicities reported. Thus, the 10.5 mg dose was selected as the recommended phase 2 dose, and 35 patients were treated in phase 2. Forty‐seven patients received ≥1 dose of the study drug and comprised the safety analysis set. The most common adverse drug reaction (ADR) was injection site reactions (ISR; 91.5%). Grade 3 ISR were common (58.8%) in phase 1 but occurred less frequently in 2 (22.9%) following implementation of risk minimization strategies. Other common ADR were pyrexia (10.6%) and febrile neutropenia (8.5%). In the efficacy analysis set, comprising patients with higher‐risk MDS after azacitidine failure in phases 1 and 2 (n = 42), the disease control rate was 19.0%, and the median overall survival (OS) was 8.6 (90% confidence interval [CI], 6.8‐10.3) months. Median OS was 10.0 (90% CI, 7.6‐11.4) months in patients with a WT1‐specific immune response (IR; n = 33) versus 4.1 (90% CI, 2.3‐8.1) months in those without a WT1‐specific IR (n = 9; P = .0034). The acceptable safety and clinical activity findings observed support the continued development of DSP‐7888 dosing emulsion. |
format | Online Article Text |
id | pubmed-8990724 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-89907242022-04-13 Phase 1/2 study evaluating the safety and efficacy of DSP‐7888 dosing emulsion in myelodysplastic syndromes Ueda, Yasunori Usuki, Kensuke Fujita, Jiro Matsumura, Itaru Aotsuka, Nobuyuki Sekiguchi, Naohiro Nakazato, Tomonori Iwasaki, Hiromi Takahara‐Matsubara, Mariko Sugimoto, Saori Goto, Masashi Naoe, Tomoki Kizaki, Masahiro Miyazaki, Yasushi Aakashi, Koichi Cancer Sci ORIGINAL ARTICLES DSP‐7888 is an immunotherapeutic cancer vaccine derived from the Wilms’ tumor gene 1 (WT1) protein. This phase 1/2 open‐label study evaluated the safety and efficacy of DSP‐7888 dosing emulsion in patients with myelodysplastic syndromes (MDS). DSP‐7888 was administered intradermally (3.5 or 10.5 mg) every 2 weeks for 6 months and then every 2‐4 weeks until lack of benefit. Twelve patients were treated in phase 1 (3.5 mg, n = 6; 10.5 mg, n = 6), with no dose‐limiting toxicities reported. Thus, the 10.5 mg dose was selected as the recommended phase 2 dose, and 35 patients were treated in phase 2. Forty‐seven patients received ≥1 dose of the study drug and comprised the safety analysis set. The most common adverse drug reaction (ADR) was injection site reactions (ISR; 91.5%). Grade 3 ISR were common (58.8%) in phase 1 but occurred less frequently in 2 (22.9%) following implementation of risk minimization strategies. Other common ADR were pyrexia (10.6%) and febrile neutropenia (8.5%). In the efficacy analysis set, comprising patients with higher‐risk MDS after azacitidine failure in phases 1 and 2 (n = 42), the disease control rate was 19.0%, and the median overall survival (OS) was 8.6 (90% confidence interval [CI], 6.8‐10.3) months. Median OS was 10.0 (90% CI, 7.6‐11.4) months in patients with a WT1‐specific immune response (IR; n = 33) versus 4.1 (90% CI, 2.3‐8.1) months in those without a WT1‐specific IR (n = 9; P = .0034). The acceptable safety and clinical activity findings observed support the continued development of DSP‐7888 dosing emulsion. John Wiley and Sons Inc. 2022-03-09 2022-04 /pmc/articles/PMC8990724/ /pubmed/34932235 http://dx.doi.org/10.1111/cas.15245 Text en © 2022 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association. https://creativecommons.org/licenses/by-nc/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc/4.0/ (https://creativecommons.org/licenses/by-nc/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes. |
spellingShingle | ORIGINAL ARTICLES Ueda, Yasunori Usuki, Kensuke Fujita, Jiro Matsumura, Itaru Aotsuka, Nobuyuki Sekiguchi, Naohiro Nakazato, Tomonori Iwasaki, Hiromi Takahara‐Matsubara, Mariko Sugimoto, Saori Goto, Masashi Naoe, Tomoki Kizaki, Masahiro Miyazaki, Yasushi Aakashi, Koichi Phase 1/2 study evaluating the safety and efficacy of DSP‐7888 dosing emulsion in myelodysplastic syndromes |
title | Phase 1/2 study evaluating the safety and efficacy of DSP‐7888 dosing emulsion in myelodysplastic syndromes |
title_full | Phase 1/2 study evaluating the safety and efficacy of DSP‐7888 dosing emulsion in myelodysplastic syndromes |
title_fullStr | Phase 1/2 study evaluating the safety and efficacy of DSP‐7888 dosing emulsion in myelodysplastic syndromes |
title_full_unstemmed | Phase 1/2 study evaluating the safety and efficacy of DSP‐7888 dosing emulsion in myelodysplastic syndromes |
title_short | Phase 1/2 study evaluating the safety and efficacy of DSP‐7888 dosing emulsion in myelodysplastic syndromes |
title_sort | phase 1/2 study evaluating the safety and efficacy of dsp‐7888 dosing emulsion in myelodysplastic syndromes |
topic | ORIGINAL ARTICLES |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8990724/ https://www.ncbi.nlm.nih.gov/pubmed/34932235 http://dx.doi.org/10.1111/cas.15245 |
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