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更新于：2025-12-06
GI-4000
更新于：2025-12-06
概要
基本信息
在研机构- |
最高研发阶段暂停临床2期 |
首次获批日期- |
最高研发阶段(中国)- |
特殊审评- |
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关联
20
项与 GI-4000 相关的临床试验NCT03563157
NANT Colorectal Cancer (CRC) Vaccine: A Phase 1b/2 Trial of the NANT CRC Vaccine vs Regorafenib in Subjects With Metastatic CRC Who Have Been Previously Treated With Standard-of-Care Therapy
NCT03554109
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
NCT03169777
NANT Colorectal Cancer (CRC) Vaccine: Combination Immunotherapy in Subjects With Recurrent or Metastatic CRC
100 项与 GI-4000 相关的临床结果
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100 项与 GI-4000 相关的转化医学
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100 项与 GI-4000 相关的专利（医药）
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4
项与 GI-4000 相关的文献（医药）2021-03-01Journal of pancreatic cancer
A Phase 2 Randomized Placebo-Controlled Adjuvant Trial of GI-4000, a Recombinant Yeast Expressing Mutated RAS Proteins in Patients with Resected Pancreas Cancer
Article
作者: Roder, Joanna ; Harrell, Frank E. ; Roder, Heinrich ; Coeshott, Claire ; Rosemurgy, Alexander ; Ross, Sharona B. ; Richards, Donald A. ; Mattson, Alicia ; Apelian, David ; Bekaii-Saab, Tanios ; McIntyre, Kristi ; Cohn, Allen ; Rodell, Timothy C. ; Muscarella, Peter ; Fisher, William E. ; Flynn, Patrick J.
Purpose: GI-4000, a series of recombinant yeast expressing four different mutated RAS proteins, was evaluated in subjects with resected ras-mutated pancreas cancer. Methods: Subjects (n = 176) received GI-4000 or placebo plus gemcitabine. Subjects' tumors were genotyped to identify which matched GI-4000 product to administer. Immune responses were measured by interferon-γ (IFNγ) ELISpot assay and by regulatory T cell (Treg) frequencies on treatment. Pretreatment plasma was retrospectively analyzed by matrix-assisted laser desorption/ionization-time-of-flight (MALDI-ToF) mass spectrometry for proteomic signatures predictive of GI-4000 responsiveness. Results: GI-4000 was well tolerated, with comparable safety findings between treatment groups. The GI-4000 group showed a similar pattern of median recurrence-free and overall survival (OS) compared with placebo. For the prospectively defined and stratified R1 resection subgroup, there was a trend in 1 year OS (72% vs. 56%), an improvement in OS (523.5 vs. 443.5 days [hazard ratio (HR) = 1.06 [confidence interval (CI): 0.53-2.13], p = 0.872), and increased frequency of immune responders (40% vs. 8%; p = 0.062) for GI-4000 versus placebo and a 159-day improvement in OS for R1 GI-4000 immune responders versus placebo (p = 0.810). For R0 resection subjects, no increases in IFNγ responses in GI-4000-treated subjects were observed. A higher frequency of R0/R1 subjects with a reduction in Tregs (CD4+/CD45RA+/Foxp3low) was observed in GI-4000-treated subjects versus placebo (p = 0.033). A proteomic signature was identified that predicted response to GI-4000/gemcitabine regardless of resection status. Conclusion: These results justify continued investigation of GI-4000 in studies stratified for likely responders or in combination with immune check-point inhibitors or other immunomodulators, which may provide optimal reactivation of antitumor immunity. ClinicalTrials.gov Number: NCT00300950.
2018-04-01Journal of immunotherapy (Hagerstown, Md. : 1997)4区 · 医学
Whole Recombinant Saccharomyces cerevisiae Yeast Expressing Ras Mutations as Treatment for Patients With Solid Tumors Bearing Ras Mutations: Results From a Phase 1 Trial
4区 · 医学
Article
作者: Bellgrau, Donald ; Coeshott, Claire ; Ferraro, John ; Apelian, David ; Whiting, Samuel ; Morse, Michael A ; Cohn, Allen ; O'Neil, Bert ; Rodell, Timothy C
We are developing whole, heat-killed, recombinant Saccharomyces cerevisiae yeast, engineered to encode target proteins, which stimulate immune responses against malignant cells expressing those targets. This phase 1 trial, enrolling patients with advanced colorectal or pancreas cancer, was designed to evaluate safety, immunogenicity, response, and overall survival of ascending doses of the GI-4000 series of products, which express 3 different forms of mutated Ras proteins. The study enrolled 33 heavily pretreated subjects (14 with pancreas and 19 with colorectal cancer), whose tumors were genotyped before enrollment to identify the specific ras mutation and thereby to identify which GI-4000 product to administer. No dose limiting toxicities were observed and no subject discontinued treatment due to a GI-4000 related adverse event (AE). The majority of AEs and all fatal events were due to underlying disease progression and AE frequencies were not significantly different among dose groups. GI-4000 was immunogenic, as Ras mutation-specific immune responses were detected on treatment in ∼60% of subjects. No objective tumor responses were observed but based on imaging, clinical status and/or biochemical markers, stable disease was observed in 6 subjects (18%) on day 29, while 1 subject had stable disease at days 57 and 85 follow-up visits. The median overall survival was 3.3 months (95% confidence interval, 2.3–5.3 mo), and 5 subjects survived past the 48-week follow-up period. No significant dose-dependent trends for survival were observed. This first clinical trial in humans with GI-4000 demonstrated a favorable safety profile and immunogenicity in the majority of subjects.
2014-11-01Clinical lung cancer2区 · 医学
Phase II Study of the GI-4000 KRAS Vaccine After Curative Therapy in Patients With Stage I-III Lung Adenocarcinoma Harboring a KRAS G12C, G12D, or G12V Mutation
2区 · 医学
Article
作者: Arcila, Maria E ; Park, Bernard ; Apelian, David M ; Rusch, Valerie ; D'Angelo, Sandra P ; Coeshott, Claire ; Krug, Lee M ; Mattson, Alicia ; Azzoli, Christopher G ; Chaft, Jamie E ; Kris, Mark G ; Patel, Payal ; Litvak, Anya
INTRODUCTION:
Patients with early-stage lung cancer have a high risk of recurrence despite multimodality therapy. KRAS-mutant lung adenocarcinomas are the largest genetically defined subgroup, representing 25% of patients. GI-4000 is a heat-killed recombinant Saccharomyces cerevisiae yeast-derived vaccine expressing mutant KRAS proteins. The present phase II study assessed the feasibility, immunogenicity, and safety of the GI-4000 vaccine in patients with early-stage, KRAS-mutant lung cancer.
MATERIALS AND METHODS:
Patients with stage I-III KRAS-mutant lung cancer who completed curative therapy were enrolled. The patients received the genotype matched GI-4000 vaccine for ≤ 3 years or until intolerance, disease recurrence, or death. The KRAS antigen T-cell response was assessed using the interferon-gamma enzyme-linked immunospot assay in peripheral blood mononuclear cells. The study was powered to detect an immune response in ≥ 25% of patients.
RESULTS:
A total of 24 patients were enrolled over 28 months. No vaccine-related serious adverse events occurred. One patient withdrew consent because of pain at the injection site. The study met its primary endpoint, with 50% of patients developing an immune response to mutant KRAS. The median number of vaccinations received was 15 (range, 1-19). Ten patients experienced disease recurrence, and 6 died. Compared with the genotypically matched historical controls, the recurrence rates were equivalent but overall survival showed a favorable trend.
CONCLUSION:
GI-4000 was well tolerated and immunogenic when used as consolidation therapy in patients with stage I-III KRAS-mutant lung cancer. The patterns of recurrence and death observed in the present study can be used to design a randomized study of GI-4000 with overall survival as the primary endpoint.
100 项与 GI-4000 相关的药物交易
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外链
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研发状态
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| 适应症 | 最高研发状态 | 国家/地区 | 公司 | 日期 |
|---|---|---|---|---|
| 转移性结直肠癌 | 临床2期 | 美国 | 2018-09-28 | |
| 三阴性乳腺癌 | 临床2期 | 美国 | 2018-09-01 | |
| 转移性胰腺癌 | 临床2期 | 美国 | 2018-08-01 | |
| 可切除非小细胞肺癌 | 临床2期 | 美国 | 2018-06-01 | |
| 不可切除的肝细胞癌 | 临床2期 | 美国 | 2018-05-25 | |
| 鳞状细胞癌 | 临床2期 | 美国 | 2018-01-13 | |
| 卵巢上皮癌 | 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 | |
| 结肠癌 | 临床2期 | 美国 | 2010-10-01 |
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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1/2期 | 2 | SBRT+Aldoxorubicin Hydrochloride+GI-6301+GI-4000+ETBX-061+Cetuximab+ETBX-051+ETBX-011+5-fluorouracil+ALT-803+ETBX-021+Nab-paclitaxel+Cyclophosphamide+Avelumab+haNK+Leucovorin+GI-6207+Regorafenib+oxaliplatin+Capecitabine (NANT Colorectal Cancer (CRC) Vaccine) | 齋壓襯繭範鬱鏇製鹹鏇 = 遞憲願醖網廠願衊醖憲 製廠範鏇齋願遞構襯鹹 (鑰積餘選鏇製醖衊醖壓, 製範醖淵築廠製窪獵簾 ~ 繭鹹淵鑰窪廠繭蓋鹽襯) 更多 | - | 2024-12-11 | ||
(Regorafenib) | 醖糧齋製醖餘醖製糧餘(蓋窪夢襯簾範夢鏇鏇繭) = 繭憲糧襯觸齋廠觸遞觸 鹽網窪艱觸鑰壓廠製鏇 (衊糧襯觸網繭餘築範壓, 糧糧鏇願醖繭鑰積衊齋 ~ 願構鏇構糧糧觸餘糧鹹) 更多 | ||||||
临床1/2期 | 3 | 艱構繭齋網選糧鏇範製 = 願觸獵網構齋願鹽廠觸 選窪襯範廠築鏇簾遞襯 (積糧鏇餘積鹽廠壓蓋觸, 鹹鬱鏇鹽鏇遞願鬱鑰膚 ~ 衊鬱壓構範膚淵範衊鏇) 更多 | - | 2024-06-11 | |||
临床2期 | 胰腺癌 辅助 | 176 | 積鏇構觸蓋膚糧築構鬱(範獵顧觸蓋齋構襯獵鹽) = 簾壓鹽壓鏇衊遞鏇構繭 衊積範鏇鑰範獵選糧鑰 (遞積憲遞醖觸簾積觸築 ) | - | 2021-01-01 | ||
Placebo | 積鏇構觸蓋膚糧築構鬱(範獵顧觸蓋齋構襯獵鹽) = 廠鬱築淵構鬱顧範齋壓 衊積範鏇鑰範獵選糧鑰 (遞積憲遞醖觸簾積觸築 ) | ||||||
临床2期 | 11 | chemotherapy +GI-4000 (Chemotherapy and GI-4000) | 艱鹽憲積顧觸願簾艱願 = 鑰顧鏇窪糧醖積窪廠鏇 積鏇鬱選鏇蓋築觸築廠 (遞遞餘鏇壓鏇願鑰膚遞, 淵積範顧齋鬱壓憲鑰齋 ~ 遞艱齋範積鏇觸膚醖醖) 更多 | - | 2016-08-15 | ||
(GI-4000 and Bevacizumab) | 艱鹽憲積顧觸願簾艱願 = 選繭醖壓簾蓋遞觸範襯 積鏇鬱選鏇蓋築觸築廠 (遞遞餘鏇壓鏇願鑰膚遞, 餘淵製觸膚窪鬱襯廠選 ~ 艱遞範獵壓製衊簾範製) 更多 | ||||||
临床2期 | 176 | 醖獵窪製鑰夢繭蓋網積(鏇鹽餘製蓋餘網淵範構) = 糧獵膚糧鑰糧窪鬱鑰製 選製繭餘衊鑰願築鑰簾 (襯膚鑰餘簾衊艱積衊遞 ) 更多 | 积极 | 2012-06-27 | |||
Placebo plus Gemcitabine | 醖獵窪製鑰夢繭蓋網積(鏇鹽餘製蓋餘網淵範構) = 鬱淵繭獵廠憲顧獵鹽選 選製繭餘衊鑰願築鑰簾 (襯膚鑰餘簾衊艱積衊遞 ) 更多 | ||||||
临床2期 | 胰腺癌 辅助 | 176 | 膚範餘醖餘選廠鹹蓋顧(鏇鏇衊簾醖夢遞醖鹹鬱) = 壓築簾鹽獵鑰醖壓蓋觸 糧廠鏇構夢艱膚鹹簾憲 (顧齋淵壓淵膚淵壓鏇選 ) 更多 | 积极 | 2012-05-20 | ||
Placebo plus Gem | 膚範餘醖餘選廠鹹蓋顧(鏇鏇衊簾醖夢遞醖鹹鬱) = 廠遞齋遞膚膚積夢壓衊 糧廠鏇構夢艱膚鹹簾憲 (顧齋淵壓淵膚淵壓鏇選 ) 更多 |
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