A phase I study of the WT2725 dosing emulsion in patients with advanced malignancies
Abstract WT2725 is a Wilms’ tumor gene 1 (WT1)-derived-oligopeptide vaccine designed to induce WT1-specific cytotoxic T-lymphocytes against WT1+ tumors in human leukocyte antigen (HLA)-A*0201+ and/or HLA-A*0206+ patients. Here, we report the results of a phase I study of WT2725. In this phase I, ope...
Guardado en:
| Autores principales: | , , , , , , , , , , , , , |
|---|---|
| Formato: | article |
| Lenguaje: | EN |
| Publicado: |
Nature Portfolio
2021
|
| Materias: | |
| Acceso en línea: | https://doaj.org/article/60746137df784b578782dc3342f39baf |
| Etiquetas: |
Agregar Etiqueta
Sin Etiquetas, Sea el primero en etiquetar este registro!
|
| id |
oai:doaj.org-article:60746137df784b578782dc3342f39baf |
|---|---|
| record_format |
dspace |
| spelling |
oai:doaj.org-article:60746137df784b578782dc3342f39baf2021-11-21T12:24:07ZA phase I study of the WT2725 dosing emulsion in patients with advanced malignancies10.1038/s41598-021-01707-32045-2322https://doaj.org/article/60746137df784b578782dc3342f39baf2021-11-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-01707-3https://doaj.org/toc/2045-2322Abstract WT2725 is a Wilms’ tumor gene 1 (WT1)-derived-oligopeptide vaccine designed to induce WT1-specific cytotoxic T-lymphocytes against WT1+ tumors in human leukocyte antigen (HLA)-A*0201+ and/or HLA-A*0206+ patients. Here, we report the results of a phase I study of WT2725. In this phase I, open-label, dose-escalation and expansion two-part study, the WT2725 dosing emulsion was administered as a monotherapy to patients with advanced malignancies known to overexpress WT1, including glioblastoma. In part 1, 44 patients were sequentially allocated to four doses: 0.3 mg (n = 5), 0.9 mg (n = 5), 3 mg (n = 6), and 9 mg (n = 28). In part 2, 18 patients were allocated to two doses: 18 mg (n = 9) and 27 mg (n = 9). No dose-limiting toxicities were observed, so the maximum tolerated dose was not reached. Median progression-free survival was 58 (95% confidence interval [CI] 56–81) days (~ 2 months) across all patients with solid tumors; median overall survival was 394 days (13.0 months) (95% CI 309–648). Overall immune-related response rate in solid tumor patients was 7.5% (95% CI 2.6–19.9); response was most prominent in the glioblastoma subgroup. Overall, 62.3% of patients were considered cytotoxic T-lymphocyte responders; the proportion increased with increasing WT2725 dosing emulsion dose. WT2725 dosing emulsion was well tolerated. Preliminary tumor response and biological marker data suggest that WT2725 dosing emulsion may exert antitumor activity in malignancies known to overexpress the WT1 protein, particularly glioblastoma, and provide a rationale for future clinical development. Trial registration: NCT01621542.Siqing FuDavid E. PiccioniHongtao LiuRimas V. LukasSantosh KesariDawit AregawiDavid S. HongKenichiro YamaguchiKate WhicherYi ZhangYu-Luan ChenNagaraju PoolaJohn EddyDavid BlumNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-11 (2021) |
| institution |
DOAJ |
| collection |
DOAJ |
| language |
EN |
| topic |
Medicine R Science Q |
| spellingShingle |
Medicine R Science Q Siqing Fu David E. Piccioni Hongtao Liu Rimas V. Lukas Santosh Kesari Dawit Aregawi David S. Hong Kenichiro Yamaguchi Kate Whicher Yi Zhang Yu-Luan Chen Nagaraju Poola John Eddy David Blum A phase I study of the WT2725 dosing emulsion in patients with advanced malignancies |
| description |
Abstract WT2725 is a Wilms’ tumor gene 1 (WT1)-derived-oligopeptide vaccine designed to induce WT1-specific cytotoxic T-lymphocytes against WT1+ tumors in human leukocyte antigen (HLA)-A*0201+ and/or HLA-A*0206+ patients. Here, we report the results of a phase I study of WT2725. In this phase I, open-label, dose-escalation and expansion two-part study, the WT2725 dosing emulsion was administered as a monotherapy to patients with advanced malignancies known to overexpress WT1, including glioblastoma. In part 1, 44 patients were sequentially allocated to four doses: 0.3 mg (n = 5), 0.9 mg (n = 5), 3 mg (n = 6), and 9 mg (n = 28). In part 2, 18 patients were allocated to two doses: 18 mg (n = 9) and 27 mg (n = 9). No dose-limiting toxicities were observed, so the maximum tolerated dose was not reached. Median progression-free survival was 58 (95% confidence interval [CI] 56–81) days (~ 2 months) across all patients with solid tumors; median overall survival was 394 days (13.0 months) (95% CI 309–648). Overall immune-related response rate in solid tumor patients was 7.5% (95% CI 2.6–19.9); response was most prominent in the glioblastoma subgroup. Overall, 62.3% of patients were considered cytotoxic T-lymphocyte responders; the proportion increased with increasing WT2725 dosing emulsion dose. WT2725 dosing emulsion was well tolerated. Preliminary tumor response and biological marker data suggest that WT2725 dosing emulsion may exert antitumor activity in malignancies known to overexpress the WT1 protein, particularly glioblastoma, and provide a rationale for future clinical development. Trial registration: NCT01621542. |
| format |
article |
| author |
Siqing Fu David E. Piccioni Hongtao Liu Rimas V. Lukas Santosh Kesari Dawit Aregawi David S. Hong Kenichiro Yamaguchi Kate Whicher Yi Zhang Yu-Luan Chen Nagaraju Poola John Eddy David Blum |
| author_facet |
Siqing Fu David E. Piccioni Hongtao Liu Rimas V. Lukas Santosh Kesari Dawit Aregawi David S. Hong Kenichiro Yamaguchi Kate Whicher Yi Zhang Yu-Luan Chen Nagaraju Poola John Eddy David Blum |
| author_sort |
Siqing Fu |
| title |
A phase I study of the WT2725 dosing emulsion in patients with advanced malignancies |
| title_short |
A phase I study of the WT2725 dosing emulsion in patients with advanced malignancies |
| title_full |
A phase I study of the WT2725 dosing emulsion in patients with advanced malignancies |
| title_fullStr |
A phase I study of the WT2725 dosing emulsion in patients with advanced malignancies |
| title_full_unstemmed |
A phase I study of the WT2725 dosing emulsion in patients with advanced malignancies |
| title_sort |
phase i study of the wt2725 dosing emulsion in patients with advanced malignancies |
| publisher |
Nature Portfolio |
| publishDate |
2021 |
| url |
https://doaj.org/article/60746137df784b578782dc3342f39baf |
| work_keys_str_mv |
AT siqingfu aphaseistudyofthewt2725dosingemulsioninpatientswithadvancedmalignancies AT davidepiccioni aphaseistudyofthewt2725dosingemulsioninpatientswithadvancedmalignancies AT hongtaoliu aphaseistudyofthewt2725dosingemulsioninpatientswithadvancedmalignancies AT rimasvlukas aphaseistudyofthewt2725dosingemulsioninpatientswithadvancedmalignancies AT santoshkesari aphaseistudyofthewt2725dosingemulsioninpatientswithadvancedmalignancies AT dawitaregawi aphaseistudyofthewt2725dosingemulsioninpatientswithadvancedmalignancies AT davidshong aphaseistudyofthewt2725dosingemulsioninpatientswithadvancedmalignancies AT kenichiroyamaguchi aphaseistudyofthewt2725dosingemulsioninpatientswithadvancedmalignancies AT katewhicher aphaseistudyofthewt2725dosingemulsioninpatientswithadvancedmalignancies AT yizhang aphaseistudyofthewt2725dosingemulsioninpatientswithadvancedmalignancies AT yuluanchen aphaseistudyofthewt2725dosingemulsioninpatientswithadvancedmalignancies AT nagarajupoola aphaseistudyofthewt2725dosingemulsioninpatientswithadvancedmalignancies AT johneddy aphaseistudyofthewt2725dosingemulsioninpatientswithadvancedmalignancies AT davidblum aphaseistudyofthewt2725dosingemulsioninpatientswithadvancedmalignancies AT siqingfu phaseistudyofthewt2725dosingemulsioninpatientswithadvancedmalignancies AT davidepiccioni phaseistudyofthewt2725dosingemulsioninpatientswithadvancedmalignancies AT hongtaoliu phaseistudyofthewt2725dosingemulsioninpatientswithadvancedmalignancies AT rimasvlukas phaseistudyofthewt2725dosingemulsioninpatientswithadvancedmalignancies AT santoshkesari phaseistudyofthewt2725dosingemulsioninpatientswithadvancedmalignancies AT dawitaregawi phaseistudyofthewt2725dosingemulsioninpatientswithadvancedmalignancies AT davidshong phaseistudyofthewt2725dosingemulsioninpatientswithadvancedmalignancies AT kenichiroyamaguchi phaseistudyofthewt2725dosingemulsioninpatientswithadvancedmalignancies AT katewhicher phaseistudyofthewt2725dosingemulsioninpatientswithadvancedmalignancies AT yizhang phaseistudyofthewt2725dosingemulsioninpatientswithadvancedmalignancies AT yuluanchen phaseistudyofthewt2725dosingemulsioninpatientswithadvancedmalignancies AT nagarajupoola phaseistudyofthewt2725dosingemulsioninpatientswithadvancedmalignancies AT johneddy phaseistudyofthewt2725dosingemulsioninpatientswithadvancedmalignancies AT davidblum phaseistudyofthewt2725dosingemulsioninpatientswithadvancedmalignancies |
| _version_ |
1718419009433501696 |