This is a single-center, randomized, single-blinded, three-arm phase Ib study of the folate binding protein vaccines E39 and J65. The study target population are patients with breast or ovarian cancer diagnosis who have been treated and are without evidence of disease. Disease-free subjects after standard of care multi-modality therapy will be screened and HLA typed. E39 and J65 are cytotoxic T-lymphocyte-eliciting peptide vaccines that are restricted to HLA-A2+ patients (approximately 50% of the U.S. population).

开始日期2013-09-30

申办/合作机构

San Antonio Military Medical Center

[+1]

NCT01580696

/ Completed临床1/2期IIT

Phase I/IIa Trial of Folate Binding Protein (FBP) Peptide (E39) Vaccine in Ovarian and Endometrial Cancer Patients

Folate binding protein (FBP) is highly over-expressed in breast, ovarian and endometrial cancers and is the source of immunogenic peptides (E39) that can stimulate cytotoxic T lymphocytes (CTL) to recognize and destroy FBP-expressing cancer cells in the laboratory. The purpose of this study is to test whether a peptide-based vaccine consisting of the E39 peptide mixed with the FDA-approved immunoadjuvant granulocyte macrophage colony-stimulating factor (GM-CSF) is safe and effective at inducing an in vivo peptide-specific immune response. Furthermore, the investigators intend to determine the best dose of the vaccine to utilize to produce this immunity most efficiently. The investigators will determine whether immunity to FBP will prevent clinical recurrence. Additionally, the investigators will compare these results with results from a trial utilizing the E75 peptide (from the HER2/neu protein) in ovarian and endometrial cancer patients in preparation for studying a combination vaccine.

开始日期2012-04-01

申办/合作机构

San Antonio Military Medical Center

100 项与 E39+GM-CSF vaccine(Galena Biopharma) 相关的临床结果

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100 项与 E39+GM-CSF vaccine(Galena Biopharma) 相关的转化医学

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100 项与 E39+GM-CSF vaccine(Galena Biopharma) 相关的专利（医药）

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项与 E39+GM-CSF vaccine(Galena Biopharma) 相关的文献（医药）

2018-07-01·Clinical Immunology3区 · 医学

Phase Ib trial of folate binding protein (FBP)-derived peptide vaccines, E39 and an attenuated version, E39’: An analysis of safety and immune response

3区 · 医学

Article

作者: Litton, Jennifer K ; Berry, John S ; Clifton, Guy T ; Vreeland, Timothy J ; Hale, Diane F ; Mittendorf, Elizabeth A ; Jackson, Doreen O ; Greene, Julia M ; Qiao, Na ; Philips, Anne V ; Peace, Kaitlin M ; Alatrash, Gheath ; Peoples, George E

In this randomized phase Ib trial, we tested combining the E39 peptide vaccine with a vaccine created from E39', an attenuated version of E39. Patients with breast or ovarian cancer, who were disease-free after standard of care therapy, were enrolled and randomized to one of three arms. Arm EE received six E39 inoculations; arm EE' received three E39 inoculations followed by three E39'; and arm E'E received three E39' inoculations, followed by three E39. Within each arm, the first five patients received 500 μg of peptide and the remainder received 1000 μg. Patients were followed for toxicity, and immune responses were measured. This initial analysis after completion of the primary vaccination series has confirmed the safety of both vaccines. Immune analyses suggest incorporating the attenuated version of the peptide improves immune responses and that sequencing of E39 followed by E39' might produce the optimal immune response.TRIAL REGISTRATIONNCT02019524.

2017-02-28·Oncotarget

Interim analysis of a phase I/IIa trial assessing E39+GM-CSF, a folate binding protein vaccine, to prevent recurrence in ovarian and endometrial cancer patients

Article

作者: Schneble, Erika J. ; Greene, Julia M. ; Darcy, Kathleen M. ; Hamilton, Chad A. ; Hale, Diane F. ; Byrd, Kevin ; Trappey, Alfred F. ; Martin, Jonathan ; Conrads, Thomas P. ; Jackson, Doreen O. ; Berry, John S. ; Peoples, George E. ; Travis Clifton, Guy ; Maxwell, George L. ; Vreeland, Timothy J. ; Hardin, Mark O. ; Herbert, Garth S. ; Elkas, John C.

BACKGROUNDFolate binding protein(FBP) is an immunogenic protein over-expressed in endometrial(EC) and ovarian cancer(OC). We are conducting a phase I/IIa trial of E39 (GALE 301)+GM-CSF, an HLA-A2-restricted, FBP-derived peptide vaccine to prevent recurrences in disease-free EC and OC patients. This interim analysis summarizes toxicity, immunologic responses, and clinical outcomes to date.METHODSHLA-A2+ patients were vaccinated(VG), and HLA-A2- or -A2+ patients were followed as controls(CG). Six monthly intradermal inoculations of E39+250mcg GM-CSF were administered to VG. Demographic, safety, immunologic, and recurrence rate(RR) data were collected and evaluated.RESULTSThis trial enrolled 51 patients; 29 in the VG and 22 in the CG. Fifteen patients received 1000mcg E39, and 14 received <1000mcg. There were no clinicopathologic differences between groups(all p ≥ 0.1). E39 was well-tolerated regardless of dose. DTH increased pre- to post-vaccination (5.7±1.5 mm vs 10.3±3.0 mm, p = 0.06) in the VG, and increased more in the 1000mcg group (3.8±2.0 mm vs 9.5±3.5 mm, p = 0.03). With 12 months median follow-up, the RR was 41% (VG) vs 55% (CG), p = 0.41. Among the 1000mcg patients, the RR was 13.3% vs 55% CG, p = 0.01. Estimated 2-year DFS was 85.7% in the 1000mcg group vs 33.6% in the CG (p = 0.021).CONCLUSIONSThis phase I/IIa trial reveals that E39+GM-CSF is well-tolerated and elicits a strong, dose-dependent in vivo immune response. Early efficacy results are promising in the 1000 mcg dose cohort. This study proves the safety and establishes the dose of E39 for a larger prospective, randomized, controlled trial in HLA-A2+ EC and OC patients to prevent recurrence.

2002-01-01·Yonsei Medical Journal4区 · 医学

The Comparison of Cytotoxic T-Lymphocyte Effects of Dendritic Cells Stimulated by the Folate Binding Protein Peptide Cultured with IL-15 and IL-2 in Solid Tumor

4区 · 医学

ArticleOA

作者: Kim, Jae Wook ; Ioannides, Constantin G. ; Kim, Young Tae ; Kim, Dong Kyu ; Kim, Jong Hwa

The current modalities for treating cancer employ not only single but multiple approaches involving surgery, radiotherapy and chemotherapy. Unfortunately, the survival outcome is not promising even with these approaches. Alternative approaches for cancer therapy are now emerging. Immunotherapy is aiming at both increasing the power, and in redirecting the specificity of the patients' immune system to attack the tumor cells. Recently, many studies using tumor associated lymphocytes (TAL) isolated from malignant ascites cultured in a media containing interleukin-2 exhibit antitumor responses. IL-2 is a lymphokine produced by T-cells. It facilitates activation, sustained growth and rescue from apoptosis. Lately, newly developed IL-15 has also exhibited antitumor activity similar to IL-2. IL-15 is a newly described cytokine produced from monocytes-marcrophages and T-cells. It has a different molecular structure but it functions like IL-2 by binding to the IL-2R beta and gammac chain. These antitumor responses are mediated by the cytotoxic T lymphocytes (CTL) that recognize the antigen in the context of the MHC molecules using the T cell receptors. CD8+-CTL recognize the peptide epitopes that are processed from the cellular proteins in the context of the MHC class I molecules. These peptides have a restricted length of 8-11 amino acids. The folate binding protein (FBP) is overexpressed in over 90% of ovarian and 20-50% in breast cancers. The FBP is the source of the antigenic peptides that are recognized by a number of these CTL-TAL, and is antigenic to both ovarian and breast cancer in vivo. To define the antitumor response of IL-15 and its' FBP immunogenicity, a peptide defining epitope E39 and E75 were presented by the PMBC derived dendritic cells (DC) from healthy donors isolated by the CD14 method to ovarian and breast CTL-TAL. Stimulating both ovarian and breast CTL- TAL by E39 or E75 pulsed DC (DC-E39, DC-E75), in the presence of IL-15 and IL-2 can rapidly enhance or induce the E39 or E75 specific CTL activity. The antitumor activities were measured by a chromium release assay for the tumor specific lysis activity using the ovarian and breast cancer cell lines. The tumor specific lysis activity for the ovarian TALs for IL-15 vs IL-2 were 28.6 +/- 3.9% and 30.3 +/- 3.2%, respectively and in the breast TALs, they were 14.8 +/- 3.1% vs 13.5 +/- 2.9%, respectively. Using autologous tumor cells, a slightly higher tumor specific lysis activity was obtained for the ovarian TALs cultured in IL-15 compared to IL-2 (72.0 +/- 8.2% vs 68.5 +/- 3.6%). However, for the breast TALs, they were 39.5 +/- 4.2% vs 41.5 +/- 3.3%, respectively. IL-15 is a newly developed cytokine that shows promising antitumor activity similar to IL-2. However, it requires lower dosage and is less toxic. Therefore, IL-15 might be a potential anticancer immunotherapeutic agent.

项与 E39+GM-CSF vaccine(Galena Biopharma) 相关的新闻（医药）

2017-03-10

·BioSpace

Bay Area’s Galena Biopharma Exploring Strategic Alternatives Just One Month After CEO Steps Down

March 10, 2017 By Mark Terry , BioSpace.com Breaking News Staff San Ramon, Calif.-based Galena Biopharma announced that it had hired Canaccord Genuity to help it develop a plan to sell the company or its assets. This comes about five weeks after its chief executive officer, Mark Schwartz , stepped down over a civil and criminal investigation into the company’s marketing of Abstral (fentanyl). The company was under investigation by the U.S. Department of Justice, looking into several employees, as well as two high-prescribing physicians, over a rebate deal between the company and the two doctors. Schwartz took over the job in 2014. At that time, the company was headquartered in Lake Oswego, Ore. Its then-CEO Mark Ahn resigned after Galena was, according to Xconomy ,“accused of tricking potential investors by allegedly paying a publicity firm to inflate its stock. Galena settled a lawsuit for $20 million in 2015 (most of it was paid by insurance).” The company indicates that it is reviewing options, including “a sale of the company, a business combination, a merger or reverse merger with another party, continuing to advance the clinical programs as a stand-alone entity, and a license or other disposition of corporate assets of the Company.” The company’s assets include GALE-401, currently in a Phase III-ready program for essential thrombocythemia, and an immune-oncology franchise for prevention of recurrence in breast and ovarian cancer, that includes NeuVax (nelipepimut-S), which has three Phase II clinical trials, a Phase IIb trial that expects to complete enrollment in the second quarter, and GALE-301 and GALE-302, which completed early-stage trials in ovarian cancer. The Phase III trial of NeuVax didn’t go well. The drug didn’t perform as well as placebo, which caused independent data monitors to recommend halting the trial, which was then officially closed on August 10, 2016. “Although the Phase III PRESENT trial of the HER2 vaccine was terminated early, after unblinding the data, it appears that the trial failed due to a design flaw in the study and not due to lack of activity of the vaccine (data to be published soon),” wrote George Peoples to Xconomy . Peoples is the San Antonio-based scientist who developed NeuVax. Galena, which was then known as RXi Pharmaceuticals and headquartered in Worcester, Mass., acquired the Arizona biotech company, Apthera , in 2011 that held the license for NeuVax. Apthera had licensed NeuVax from the MD Anderson Cancer Center in Houston and the Henry Jackson Foundation in 2006. Not surprisingly, Galena has tanked recently. Shares are currently trading for $0.59. Shares traded at $45.40 on June 22, 2016, before they plunged to $7 on June 29, 2016. The stock has a one-year high of $49.80 and a one-year low of $0.21. Its 50-day moving average is $1.09 and its 200-day moving average is $1.21. On February 6, FBR analyst Vernon Bernardino downgraded the stock to “Hold,” with a price target of $4. On February 2, Jason McCarthy , an analyst with Maxim , downgraded the stock to “Hold.”

临床2期并购临床3期疫苗高管变更

100 项与 E39+GM-CSF vaccine(Galena Biopharma) 相关的药物交易

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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
乳腺癌	临床2期	美国	The University of Texas MD Anderson Cancer Center	2013-09-30
子宫内膜癌	临床2期	美国	San Antonio Military Medical Center	2012-04-01
输卵管癌	临床2期	美国	San Antonio Military Medical Center	2012-04-01
卵巢癌	临床2期	美国	San Antonio Military Medical Center	2012-04-01
腹膜癌	临床2期	美国	San Antonio Military Medical Center	2012-04-01

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临床结果

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研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


AACR2016	临床1期	卵巢癌	51	E39’	(糧淵鑰鏇築齋淵糧選餘) = 積鏇鑰鬱蓋壓憲願膚範壓選範醖鑰壓夢膚憲淵 (蓋繭構憲願網網艱廠積 )	积极	2016-07-15
				E39 + GM-CSF	(糧淵鑰鏇築齋淵糧選餘) = 鏇鹽積壓範窪鹹製餘鹽壓選範醖鑰壓夢膚憲淵 (蓋繭構憲願網網艱廠積 )
NCT01580696 (ASCO2015)	临床1期	卵巢子宫内膜样癌辅助	51	E39 + GM-CSF 1000 mcg	網築築齋築窪選醖製窪(膚壓遞衊遞觸獵艱鬱顧) = 膚餘壓鹹顧膚選憲觸淵鹹夢鑰獵構膚網製鹹獵 (襯襯顧廠襯憲願鏇築廠 ) 更多	-	2015-05-20
				folate binding protein vaccine (E39+GM-CSF) (Control group)	網築築齋築窪選醖製窪(膚壓遞衊遞觸獵艱鬱顧) = 鑰醖簾壓襯蓋鬱膚範顧鹹夢鑰獵構膚網製鹹獵 (襯襯顧廠襯憲願鏇築廠 ) 更多