Safety and immunogenicity of neoadjuvant treatment using WT1-immunotherapeutic in combination with standard therapy in patients with WT1-positive Stage II/III breast cancer : a randomized Phase I study
PURPOSE: This Phase I, multicenter, randomized study (ClinicalTrials.gov NCT01220128) evaluated the safety and immunogenicity of recombinant Wilms' tumor 1 (WT1) protein combined with the immunostimulant AS15 (WT1-immunotherapeutic) as neoadjuvant therapy administered concurrently with standard treatments in WT1-positive breast cancer patients.
METHODS: Patients were treated in 4 cohorts according to neoadjuvant treatment (A: post-menopausal, hormone receptor [HR]-positive patients receiving aromatase inhibitors; B: patients receiving chemotherapy; C: HER2-overexpressing patients on trastuzumab-chemotherapy combination; D: HR-positive/HER2-negative patients on chemotherapy). Patients (cohorts A-C) were randomized (2:1) to receive 6 or 8 doses of WT1-immunotherapeutic or placebo together with standard neoadjuvant treatment in a double-blind manner; cohort D patients received WT1-immunotherapeutic in an open manner. Safety was assessed throughout the study. WT1-specific antibodies were assessed pre- and post-vaccination.
RESULTS: Sixty-two patients were randomized; 60 received ≥ one dose of WT1-immunotherapeutic. Two severe toxicities were reported: diarrhea (cohort C; also reported as a grade 3 serious adverse event) and decreased left ventricular ejection fraction (cohort B; also reported as a grade 2 adverse event). Post-dose 4 of WT1-immunotherapeutic, 10/10 patients from cohort A, 0/8 patients from cohort B, 6/11 patients from cohort C, and 2/3 patients from cohort D were humoral responders. The sponsor elected to close the trial prematurely.
CONCLUSIONS: Concurrent administration of WT1-immunotherapeutic and standard neoadjuvant therapy was well tolerated and induced WT1-specific antibodies in patients receiving neoadjuvant aromatase inhibitors. In patients on neoadjuvant chemotherapy or trastuzumab-chemotherapy combination, the humoral response was impaired or blunted, likely due to either co-administration of corticosteroids and/or the chemotherapies themselves.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2017 |
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| Erschienen: |
2017 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:162 |
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| Enthalten in: |
Breast cancer research and treatment - 162(2017), 3 vom: 07. Apr., Seite 479-488 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Higgins, M [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 07.12.2017 Date Revised 03.01.2021 published: Print-Electronic ClinicalTrials.gov: NCT01220128, NCT01220128 Citation Status MEDLINE |
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| doi: |
10.1007/s10549-017-4130-y |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM268761183 |
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| 100 | 1 | |a Higgins, M |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Safety and immunogenicity of neoadjuvant treatment using WT1-immunotherapeutic in combination with standard therapy in patients with WT1-positive Stage II/III breast cancer |b a randomized Phase I study |
| 264 | 1 | |c 2017 | |
| 336 | |a Text |b txt |2 rdacontent | ||
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| 500 | |a Date Completed 07.12.2017 | ||
| 500 | |a Date Revised 03.01.2021 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a ClinicalTrials.gov: NCT01220128, NCT01220128 | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a PURPOSE: This Phase I, multicenter, randomized study (ClinicalTrials.gov NCT01220128) evaluated the safety and immunogenicity of recombinant Wilms' tumor 1 (WT1) protein combined with the immunostimulant AS15 (WT1-immunotherapeutic) as neoadjuvant therapy administered concurrently with standard treatments in WT1-positive breast cancer patients | ||
| 520 | |a METHODS: Patients were treated in 4 cohorts according to neoadjuvant treatment (A: post-menopausal, hormone receptor [HR]-positive patients receiving aromatase inhibitors; B: patients receiving chemotherapy; C: HER2-overexpressing patients on trastuzumab-chemotherapy combination; D: HR-positive/HER2-negative patients on chemotherapy). Patients (cohorts A-C) were randomized (2:1) to receive 6 or 8 doses of WT1-immunotherapeutic or placebo together with standard neoadjuvant treatment in a double-blind manner; cohort D patients received WT1-immunotherapeutic in an open manner. Safety was assessed throughout the study. WT1-specific antibodies were assessed pre- and post-vaccination | ||
| 520 | |a RESULTS: Sixty-two patients were randomized; 60 received ≥ one dose of WT1-immunotherapeutic. Two severe toxicities were reported: diarrhea (cohort C; also reported as a grade 3 serious adverse event) and decreased left ventricular ejection fraction (cohort B; also reported as a grade 2 adverse event). Post-dose 4 of WT1-immunotherapeutic, 10/10 patients from cohort A, 0/8 patients from cohort B, 6/11 patients from cohort C, and 2/3 patients from cohort D were humoral responders. The sponsor elected to close the trial prematurely | ||
| 520 | |a CONCLUSIONS: Concurrent administration of WT1-immunotherapeutic and standard neoadjuvant therapy was well tolerated and induced WT1-specific antibodies in patients receiving neoadjuvant aromatase inhibitors. In patients on neoadjuvant chemotherapy or trastuzumab-chemotherapy combination, the humoral response was impaired or blunted, likely due to either co-administration of corticosteroids and/or the chemotherapies themselves | ||
| 650 | 4 | |a Clinical Trial, Phase I | |
| 650 | 4 | |a Clinical Trial, Phase II | |
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Multicenter Study | |
| 650 | 4 | |a Randomized Controlled Trial | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a Breast cancer | |
| 650 | 4 | |a Immunogenicity | |
| 650 | 4 | |a Immunotherapy | |
| 650 | 4 | |a Neoadjuvant therapy | |
| 650 | 4 | |a Safety | |
| 650 | 4 | |a WT1 antigen | |
| 650 | 7 | |a Antibodies |2 NLM | |
| 650 | 7 | |a Antigens, Neoplasm |2 NLM | |
| 650 | 7 | |a Cancer Vaccines |2 NLM | |
| 650 | 7 | |a Recombinant Proteins |2 NLM | |
| 650 | 7 | |a WT1 Proteins |2 NLM | |
| 700 | 1 | |a Curigliano, G |e verfasserin |4 aut | |
| 700 | 1 | |a Dieras, V |e verfasserin |4 aut | |
| 700 | 1 | |a Kuemmel, S |e verfasserin |4 aut | |
| 700 | 1 | |a Kunz, G |e verfasserin |4 aut | |
| 700 | 1 | |a Fasching, P A |e verfasserin |4 aut | |
| 700 | 1 | |a Campone, M |e verfasserin |4 aut | |
| 700 | 1 | |a Bachelot, T |e verfasserin |4 aut | |
| 700 | 1 | |a Krivorotko, P |e verfasserin |4 aut | |
| 700 | 1 | |a Chan, S |e verfasserin |4 aut | |
| 700 | 1 | |a Ferro, A |e verfasserin |4 aut | |
| 700 | 1 | |a Schwartzberg, L |e verfasserin |4 aut | |
| 700 | 1 | |a Gillet, M |e verfasserin |4 aut | |
| 700 | 1 | |a De Sousa Alves, P M |e verfasserin |4 aut | |
| 700 | 1 | |a Wascotte, V |e verfasserin |4 aut | |
| 700 | 1 | |a Lehmann, F F |e verfasserin |4 aut | |
| 700 | 1 | |a Goss, P |e verfasserin |4 aut | |
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