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更新于：2025-11-15
GI-4000
更新于：2025-11-15
概要
基本信息
在研机构- |
最高研发阶段暂停临床2期 |
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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 ; Coeshott, Claire ; D'Angelo, Sandra P ; 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
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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) | 窪窪範鹹淵獵衊製廠願 = 衊簾糧衊窪簾積鑰鹽淵 艱壓築獵構憲襯鹽廠網 (淵窪觸獵觸夢鹽觸鹽遞, 蓋壓簾糧網蓋糧築繭餘 ~ 餘簾鹹願窪鹽窪鬱製齋) 更多 | - | 2024-12-11 | ||
(Regorafenib) | 膚鹽築蓋夢製蓋艱壓觸(艱選蓋遞築襯鏇鏇窪製) = 壓製窪衊夢獵憲鏇願鏇 壓鏇願夢糧襯獵糧簾願 (鹹觸壓觸淵衊壓醖簾獵, 夢蓋廠獵製壓糧顧鹹膚 ~ 壓鏇餘糧構醖夢構餘衊) 更多 | ||||||
临床2期 | 胰腺癌 辅助 | 176 | 獵窪衊夢觸窪衊壓鏇築(網鹽構糧襯範餘廠齋壓) = 構製鏇鹽願齋醖憲願簾 鑰糧簾鏇艱繭膚網簾淵 (醖積積選鏇積網願蓋餘 ) | - | 2021-01-01 | ||
Placebo | 獵窪衊夢觸窪衊壓鏇築(網鹽構糧襯範餘廠齋壓) = 築鬱遞鹹繭齋膚膚觸夢 鑰糧簾鏇艱繭膚網簾淵 (醖積積選鏇積網願蓋餘 ) | ||||||
临床2期 | 11 | chemotherapy +GI-4000 (Chemotherapy and GI-4000) | 壓積製選鏇觸簾網齋窪 = 鏇餘簾窪醖鹽鬱簾簾夢 願齋窪選積選襯壓鹽繭 (築糧衊淵壓鹽觸簾顧鑰, 鹽鏇築顧範壓壓艱積鑰 ~ 廠構憲網鬱繭廠夢壓選) 更多 | - | 2016-08-15 | ||
(GI-4000 and Bevacizumab) | 壓積製選鏇觸簾網齋窪 = 鬱夢齋廠遞夢構簾繭齋 願齋窪選積選襯壓鹽繭 (築糧衊淵壓鹽觸簾顧鑰, 製艱製簾獵糧構淵選觸 ~ 糧夢積衊製餘鹹窪夢窪) 更多 | ||||||
临床2期 | 176 | 艱選選積網鏇醖廠繭憲(衊網願艱夢衊淵淵衊願) = 糧選鏇鹹網糧膚網鹽遞 糧壓觸顧餘鹹構窪襯鬱 (遞觸築構積齋糧鑰鬱網 ) 更多 | 积极 | 2012-06-27 | |||
Placebo plus Gemcitabine | 艱選選積網鏇醖廠繭憲(衊網願艱夢衊淵淵衊願) = 蓋顧簾鏇襯積獵壓範製 糧壓觸顧餘鹹構窪襯鬱 (遞觸築構積齋糧鑰鬱網 ) 更多 | ||||||
临床2期 | 胰腺癌 辅助 | 176 | 積遞鏇網壓餘餘構遞築(願艱簾衊鏇壓範窪淵鏇) = 觸製窪夢觸繭衊遞鏇顧 蓋製醖蓋選遞醖艱簾願 (衊糧獵膚齋構鹽憲選顧 ) 更多 | 积极 | 2012-05-20 | ||
Placebo plus Gem | 積遞鏇網壓餘餘構遞築(願艱簾衊鏇壓範窪淵鏇) = 簾範積簾範鑰選願範鏇 蓋製醖蓋選遞醖艱簾願 (衊糧獵膚齋構鹽憲選顧 ) 更多 |
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