更新于：2024-06-20
Brachyury peptide vaccine(GlobeImmune, Inc.)
更新于：2024-06-20
概要
基本信息
最高研发阶段临床2期 |
首次获批日期- |
最高研发阶段(中国)- |
特殊审评- |
关联
21
项与 Brachyury peptide vaccine(GlobeImmune, Inc.) 相关的临床试验Randomized Phase 2 Clinical Trial of Nab-Paclitaxel + Durvalumab (MEDI4736) + Tremelimumab + Neoantigen Vaccine Vs. Nab-Paclitaxel + Durvalumab (MEDI4736) + Tremelimumab in Patients With Metastatic Triple Negative Breast Cancer
QUILT-2.024: Phase 2 Neoadjuvant, Consolidation, and Adjuvant Combination NANT Immunotherapy Versus Standard of Care in Subjects With Resectable Non-small Cell Lung Cancer
An Open-Label Randomized Phase 2 Trial Of The NANT NEOADJUVANT Triple-Negative Breast Cancer (TNBC) VACCINE VS Standard-Of-Care For The Neoadjuvant Treatment Of Subjects With TNBC
100 项与 Brachyury peptide vaccine(GlobeImmune, Inc.) 相关的临床结果
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100 项与 Brachyury peptide vaccine(GlobeImmune, Inc.) 相关的转化医学
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100 项与 Brachyury peptide vaccine(GlobeImmune, Inc.) 相关的专利（医药）
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4
项与 Brachyury peptide vaccine(GlobeImmune, Inc.) 相关的文献（医药）2023-08-01Cancer immunology, immunotherapy : CII
Brachyury-targeted immunotherapy combined with gemcitabine against head and neck cancer.
Article
作者: Nagato, Toshihiro ; Komatsuda, Hiroki ; Hayashi, Tatsuya ; Hayashi, Ryusuke ; Kono, Michihisa ; Kosaka, Akemi ; Takahara, Miki ; Yamaki, Hidekiyo ; Katada, Akihiro ; Ohkuri, Takayuki ; Wakisaka, Risa ; Kumai, Takumi ; Sato, Ryosuke ; Ohara, Kenzo ; Kishibe, Kan ; Kobayashi, Hiroya
Brachyury is a transcription factor belonging to the T-box gene family and is involved in the posterior formation of the mesoderm and differentiation of chordates. As the overexpression of Brachyury is a poor prognostic factor in a variety of cancers, the establishment of Brachyury-targeted therapy would be beneficial for the treatment of aggressive tumors. Because transcription factors are difficult to treat with a therapeutic antibody, peptide vaccines are a feasible approach for targeting Brachyury. In this study, we identified Brachyury-derived epitopes that elicit antigen-specific and tumor-reactive CD4+ T cells that directly kill tumors. T cells recognizing Brachyury epitopes were present in patients with head and neck squamous cell carcinoma. Next, we focused on gemcitabine (GEM) as an immunoadjuvant to augment the efficacy of antitumor responses by T cells. Interestingly, GEM upregulated HLA class I and HLA-DR expression in tumor, followed by the upregulation of anti-tumor T cell responses. As tumoral PD-L1 expression was also augmented by GEM, PD-1/PD-L1 blockade and GEM synergistically enhanced the tumor-reactivity of Brachyury-reactive T cells. The synergy between the PD-1/PD-L1 blockade and GEM was also confirmed in a mouse model of head and neck squamous cell carcinoma. These results suggest that the combined treatment of Brachyury peptide with GEM and immune checkpoint blockade could be a promising immunotherapy against head and neck cancer.
2021-05-01The oncologist2区 · 医学
Randomized, Double-Blind, Placebo-Controlled Phase II Study of Yeast-Brachyury Vaccine (GI-6301) in Combination with Standard-of-Care Radiotherapy in Locally Advanced, Unresectable Chordoma
2区 · 医学
Article
作者: Marté, Jennifer L. ; Gilbert, Mark R. ; Bilusic, Marijo ; DeMaria, Peter Joseph ; Donahue, Renee N. ; Shen, Victoria ; Strauss, Julius ; Madan, Ravi A. ; Park, Deric M. ; Gulley, James L. ; Schlom, Jeffrey ; Heery, Christopher R. ; Bagheri, Mohammad Hadi ; Steinberg, Seth M.
Abstract:
Background:
Brachyury is a transcription factor overexpressed in chordoma and is associated with chemotherapy resistance and epithelial-to-mesenchymal transition. GI-6301 is a recombinant, heat-killed Saccharomyces cerevisiae yeast-based vaccine targeting brachyury. A previous phase I trial of GI-6301 demonstrated a signal of clinical activity in chordomas. This trial evaluated synergistic effects of GI-6301 vaccine plus radiation.
Materials and Methods:
Adults with locally advanced, unresectable chordoma were treated on a randomized, placebo-controlled trial. Patients received three doses of GI-6301 (80 × 107 yeast cells) or placebo followed by radiation, followed by continued vaccine or placebo until progression. Primary endpoint was overall response rate, defined as a complete response (CR) or partial response (PR) in the irradiated tumor site at 24 months. Immune assays were conducted to evaluate immunogenicity.
Results:
Between May 2015 and September 2019, 24 patients enrolled on the first randomized phase II study in chordoma. There was one PR in each arm; no CRs were observed. Median progressive-free survival for vaccine and placebo arms was 20.6 months (95% confidence interval [CI], 5.7–37.5 months) and 25.9 months (95% CI, 9.2–30.8 months), respectively. Hazard ratio was 1.02 (95% CI, 0.38–2.71). Vaccine was well tolerated with no vaccine-related serious adverse events. Preexisting brachyury-specific T cells were detected in most patients in both arms. Most patients developed T-cell responses during therapy, with no difference between arms in frequency or magnitude of response.
Conclusion:
No difference in overall response rate was observed, leading to early discontinuation of this trial due to low conditional power to detect statistical difference at the planned end of accrual.
Implications for Practice:
Chordoma is a rare neoplasm lacking effective systemic therapies for advanced, unresectable disease. Lack of clinically actionable somatic mutations in chordoma makes development of targeted therapy quite challenging. While the combination of yeast-brachyury vaccine (GI-6301) and standard radiation therapy did not demonstrate synergistic antitumor effects, brachyury still remains a good target for developmental therapeutics in chordoma. Patients and their oncologists should consider early referral to centers with expertise in chordoma (or sarcoma) and encourage participation in clinical trials.
2015-11-01Cancer immunology research1区 · 医学
Phase I Trial of a Yeast-Based Therapeutic Cancer Vaccine (GI-6301) Targeting the Transcription Factor Brachyury
1区 · 医学
Article
作者: Singh, B. Harpreet ; Grenga, Italia ; Madan, Ravi A. ; Rodell, Timothy C. ; Gulley, James L. ; Arlen, Philip M. ; Marté, Jennifer L. ; Rauckhorst, Myrna ; Schlom, Jeffrey ; Donahue, Renee N. ; Dahut, William ; Heery, Christopher R.
Abstract:
The nuclear transcription factor brachyury has previously been shown to be a strong mediator of the epithelial-to-mesenchymal transition (EMT) in human carcinoma cells and a strong negative prognostic factor in several tumor types. Brachyury is overexpressed in a range of human carcinomas as well as in chordoma, a rare tumor for which there is no standard systemic therapy. Preclinical studies have shown that a recombinant Saccharomyces cerevisiae (yeast) vaccine encoding brachyury (GI-6301) can activate human T cells in vitro. A phase I dose-escalation (3+3 design) trial enrolled 34 patients at 4 dose levels [3, 3, 16, and 11 patients, respectively, at 4, 16, 40, and 80 yeast units (YU)]. Expansion cohorts were enrolled at 40- and 80-YU dose levels for analysis of immune response and clinical activity. We observed brachyury-specific T-cell immune responses in the majority of evaluable patients despite most having been heavily pretreated. No evidence of autoimmunity or other serious adverse events was observed. Two chordoma patients showed evidence of disease control (one mixed response and one partial response). A patient with colorectal carcinoma, who enrolled on study with a large progressing pelvic mass and rising carcinoembryonic antigen (CEA), remains on study for greater than 1 year with stable disease, evidence of decreased tumor density, and decreased serum CEA. This is the first-in-human study to demonstrate the safety and immunogenicity of this therapeutic cancer vaccine and provides the rationale for exploration in phase II studies. A randomized phase II chordoma study is now enrolling patients. Cancer Immunol Res; 3(11); 1248–56. ©2015 AACR.
1
项与 Brachyury peptide vaccine(GlobeImmune, Inc.) 相关的新闻（医药）2022-10-22
抗体疫苗抗体药物偶联物信使RNA小分子药物
100 项与 Brachyury peptide vaccine(GlobeImmune, Inc.) 相关的药物交易
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研发状态
10 条进展最快的记录, 后查看更多信息
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| 适应症 | 最高研发状态 | 国家/地区 | 公司 | 日期 |
|---|---|---|---|---|
| 胰腺癌 | 临床2期 | 美国 | 2018-08-01 | |
| 结直肠癌 | 临床2期 | 美国 | 2018-05-25 | |
| 肝细胞癌 | 临床2期 | 美国 | 2018-05-25 | |
| 乳腺癌 | 临床2期 | 美国 | - | 2018-03-06 |
| 非小细胞肺癌 | 临床2期 | - | 2018-02-01 | |
| 鳞状细胞癌 | 临床2期 | 美国 | 2018-01-13 | |
| 黑色素瘤 | 临床2期 | - | 2017-12-01 | |
| 梅克尔细胞癌 | 临床2期 | - | 2017-12-01 | |
| 头颈部鳞状细胞癌 | 临床2期 | - | 2017-12-01 | |
| 尿路上皮癌 | 临床2期 | - | 2017-12-01 |
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临床结果
临床结果
适应症
分期
评价
查看全部结果
临床2期 | 24 | Radiotherapy+GI-6301 Vaccine (Yeast- Brachyury) (GI-6301 Vaccine) | 積醖鏇顧醖壓網壓鹽餘(網築壓醖願壓窪範艱鏇) = 蓋鏇繭鹽廠網餘鑰鹽獵 夢製製顧鑰蓋繭蓋構鹹 (襯鏇淵膚鏇鏇鑰鏇積憲, 繭製築糧衊壓衊鑰淵願 ~ 觸餘窪艱範夢鑰夢壓醖) 更多 | - | 2024-05-20 | ||
Radiotherapy (Placebo) | 積醖鏇顧醖壓網壓鹽餘(網築壓醖願壓窪範艱鏇) = 衊醖製網鏇廠襯鏇選壓 夢製製顧鑰蓋繭蓋構鹹 (襯鏇淵膚鏇鏇鑰鏇積憲, 遞窪鑰繭構夢醖簾觸築 ~ 憲觸窪淵顧膚鑰膚夢願) 更多 | ||||||
临床2期 | 22 | photon or proton RT+GI-6301 | 餘遞壓鑰積願顧襯醖鏇(蓋壓製繭壓齋窪壓鏇網) = 淵淵衊蓋齋齋糧壓窪鏇 鹽觸醖願選範獵繭遞廠 (餘膚繭獵鹽鏇網築積鹽 ) 更多 | 不佳 | 2020-05-29 | ||
photon or proton RT+placebo | 餘遞壓鑰積願顧襯醖鏇(蓋壓製繭壓齋窪壓鏇網) = 製襯鹹顧齋蓋齋窪憲鑰 鹽觸醖願選範獵繭遞廠 (餘膚繭獵鹽鏇網築積鹽 ) 更多 | ||||||
临床1期 | 34 | (4 YU (Dose Level 1)) | 艱窪齋獵願醖鬱糧簾鹹(鏇壓繭簾蓋壓網鏇範鏇) = 夢淵窪鹹鬱鑰選顧齋鬱 構鹽窪糧壓膚繭衊構醖 (構獵鬱壓壓構願範艱網, 憲襯餘觸範鬱鏇衊選衊 ~ 顧壓繭構襯膚網築襯獵) 更多 | - | 2017-07-31 | ||
(16 YU (Dose Level 2)) | 艱窪齋獵願醖鬱糧簾鹹(鏇壓繭簾蓋壓網鏇範鏇) = 餘築簾繭窪顧願網醖窪 構鹽窪糧壓膚繭衊構醖 (構獵鬱壓壓構願範艱網, 衊鹹鏇壓鑰淵襯製顧鬱 ~ 積憲積鑰蓋獵膚顧憲淵) 更多 | ||||||
临床1期 | 7 | 網齋艱顧襯網壓鏇繭遞(構壓願獵鏇淵顧糧積廠) = 遞蓋膚餘艱夢壓衊範繭 鹹夢構蓋製範繭繭壓構 (選製糧糧壓蓋選鹹衊蓋 ) | - | 2014-05-20 | |||
临床1期 | 27 | 範艱壓積願餘簾願鏇網(壓積鑰齋壓壓衊觸淵廠) = 鑰築範廠積願鑰窪選獵 壓觸齋蓋遞憲簾廠窪製 (製顧憲餘鏇膚齋蓋築鹽 ) 更多 | - | 2014-05-20 |
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