Delving into the Latest Updates on E39+GM-CSF vaccine(Galena Biopharma) with Synapse

Overview

Basic Info

Drug Type

Synthetic peptide vaccine, Therapeutic vaccine

Synonyms

DC-E39, E39 peptide vaccine, Folate Binding Protein-E39 vaccine

+ [3]

Target-

Action

stimulants

Mechanism

Immunostimulants, T lymphocytes stimulants

Therapeutic Areas

NeoplasmsEndocrinology and Metabolic DiseaseUrogenital Diseases+ [1]

Active Indication

Breast CancerOvarian Cancer

Inactive Indication

Endometrial CarcinomaFallopian Tube CarcinomaPeritoneal Neoplasms

Originator Organization

SELLAS Life Sciences Group, Inc.

Active Organization

The University of Texas MD Anderson Cancer Center

Inactive Organization

San Antonio Military Medical Center

License Organization-

Drug Highest PhasePreclinical

First Approval Date-

Regulation-

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Structure/Sequence

Sequence Code 9531327

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).

Start Date30 Sep 2013

Sponsor / Collaborator

San Antonio Military Medical Center

[+1]

NCT01580696

/ CompletedPhase 1/2IIT

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.

Start Date01 Apr 2012

Sponsor / Collaborator

San Antonio Military Medical Center

100 Clinical Results associated with E39+GM-CSF vaccine(Galena Biopharma)

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100 Translational Medicine associated with E39+GM-CSF vaccine(Galena Biopharma)

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100 Patents (Medical) associated with E39+GM-CSF vaccine(Galena Biopharma)

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5

Literatures (Medical) associated with E39+GM-CSF vaccine(Galena Biopharma)

01 Jul 2018·Clinical immunology (Orlando, Fla.)Q3 · MEDICINE

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

Q3 · MEDICINE

Article

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

TRIAL REGISTRATION:

NCT02019524.

28 Feb 2017·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

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

BACKGROUND:

Folate 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.

METHODS:

HLA-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.

RESULTS:

This 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).

CONCLUSIONS:

This 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.

01 Jan 2002·Yonsei medical journalQ4 · MEDICINE

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

Q4 · MEDICINE

ArticleOA

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

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.

1

News (Medical) associated with E39+GM-CSF vaccine(Galena Biopharma)

10 Mar 2017

·www.biospace.com

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.”

Phase 2AcquisitionPhase 3VaccineExecutive Change

100 Deals associated with E39+GM-CSF vaccine(Galena Biopharma)

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R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Endometrial Carcinoma	Phase 2	United States	San Antonio Military Medical Center	01 Apr 2012
Fallopian Tube Carcinoma	Phase 2	United States	San Antonio Military Medical Center	01 Apr 2012
Ovarian Cancer	Phase 2	United States	San Antonio Military Medical Center	01 Apr 2012
Peritoneal Neoplasms	Phase 2	United States	San Antonio Military Medical Center	01 Apr 2012
Breast Cancer	Phase 1	United States	San Antonio Military Medical Center	30 Sep 2013

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT01580696 (ASCO2016)	Phase 1	Endometrioid carcinoma ovary	51	E39 + 250 mcg GM-CSF	ugqanncvlf(gnpuxtldwm) = ivaelbzdyx ufqojhittk (gfqguxhfjp ) View more	-	20 May 2016
				E39 + GM-CSF (Control group)	ugqanncvlf(gnpuxtldwm) = gtuwkwvgzf ufqojhittk (gfqguxhfjp ) View more
NCT01580696 (ASCO2015)	Phase 1	Endometrioid carcinoma ovary Adjuvant	51	E39 + GM-CSF 1000 mcg	wkkvmahpji(wekmorsrwl) = valljvovgl blklyiaiox (mcidacdjfq ) View more	-	20 May 2015
				folate binding protein vaccine (E39+GM-CSF) (Control group)	wkkvmahpji(wekmorsrwl) = vibeqgcwxx blklyiaiox (mcidacdjfq ) View more
NCT01580696 (Phase I/IIa Trial of Folate Binding Protein Vaccine in Ovarian Cancer, SITC2014)	Phase 2	Ovarian Cancer \| Endometrial Carcinoma Adjuvant HLA-A2-	47	Vaccine Group (VG)	zmxzlnzdgt(tkxttdfcol) = ebqilqrpvc inakolexrt (tlubfyqqcb ) View more	Positive	06 Nov 2014
				folate binding protein (FBP) adjuvant cancer vaccine (E39+GM-CSF) (Control Group (CG))	zmxzlnzdgt(tkxttdfcol) = qztsxtqjcc inakolexrt (tlubfyqqcb ) View more