Delving into the Latest Updates on Brachyury peptide vaccine(GlobeImmune, Inc.) with Synapse

Overview

Basic Info

Drug Type

Personalized antigen vaccine, Therapeutic vaccine

Synonyms

Brachyury peptide vaccine, Yeast brachyury vaccine

Target

TBXT

Mechanism

TBXT modulators(T-box transcription factor T modulators)

Therapeutic Areas

Neoplasms

Active Indication

Germ Cell and Embryonal Neoplasms

Inactive Indication

AdenocarcinomaChordomaColonic Cancer+ [10]

Originator Organization

GlobeImmune, Inc.

Active Organization

GlobeImmune, Inc.

Inactive Organization

ImmunityBio, Inc.

NantKwest, Inc.

National Cancer Institute

Drug Highest PhasePhase 2

First Approval Date-

Regulation-

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This phase II trial studies how well nab-paclitaxel, durvalumab, and tremelimumab with or without personalized synthetic long peptide vaccine (neoantigen vaccine) works in treating patients with triple negative breast cancer that has spread from where it first started (primary site) to other places in the body (metastatic). Chemotherapy drugs, such as nab-paclitaxel, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Immunotherapy with monoclonal antibodies, such as durvalumab and tremelimumab, may induce changes in body's immune system and may interfere with the ability of tumor cells to grow and spread. Vaccines made from peptides may help the body build an effective immune response to kill tumor cells. It is not yet known whether giving nab-paclitaxel, durvalumab, and tremelimumab with or without neoantigen vaccine will work better in treating patients with triple negative breast cancer.

Start Date13 Apr 2021

Sponsor / Collaborator

National Cancer Institute

NCT03554109 / WithdrawnPhase 2

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

This is a randomized open-label phase 2 study to evaluate the efficacy and safety (as assessed by pCR) of the NANT Neoadjuvant TNBC Vaccine regimen (experimental arm) compared to the SoC dose-dense regimen of doxorubicin/cyclophosphamide followed by paclitaxel (control arm).

Start Date01 Sep 2018

Sponsor / Collaborator

ImmunityBio, Inc.

NCT03574649 / WithdrawnPhase 2

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

This is a randomized phase 2 study to compare the efficacy of neoadjuvant, consolidation, and adjuvant immunotherapy (NANT NSCLC Combination Immunotherapy; experimental arm) to standard of care (surgery and adjuvant chemotherapy; control arm) in subjects with stage II-IIIa resectable NSCLC.

Start Date01 Sep 2018

Sponsor / Collaborator

ImmunityBio, Inc.

100 Clinical Results associated with Brachyury peptide vaccine(GlobeImmune, Inc.)

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100 Translational Medicine associated with Brachyury peptide vaccine(GlobeImmune, Inc.)

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100 Patents (Medical) associated with Brachyury peptide vaccine(GlobeImmune, Inc.)

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4

Literatures (Medical) associated with Brachyury peptide vaccine(GlobeImmune, Inc.)

01 Aug 2023·Cancer immunology, immunotherapy : CII

Brachyury-targeted immunotherapy combined with gemcitabine against head and neck cancer.

Article

Author: Kobayashi, Hiroya ; Katada, Akihiro ; Yamaki, Hidekiyo ; Nagato, Toshihiro ; Kosaka, Akemi ; Kishibe, Kan ; Kumai, Takumi ; Wakisaka, Risa ; Sato, Ryosuke ; Takahara, Miki ; Komatsuda, Hiroki ; Kono, Michihisa ; Ohara, Kenzo ; Ohkuri, Takayuki ; Hayashi, Ryusuke ; Hayashi, Tatsuya

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.

01 May 2021·The OncologistQ2 · MEDICINE

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

Q2 · MEDICINE

Article

Author: Marté, Jennifer L. ; Heery, Christopher R. ; Park, Deric M. ; Gilbert, Mark R. ; DeMaria, Peter Joseph ; Bagheri, Mohammad Hadi ; Strauss, Julius ; Donahue, Renee N. ; Madan, Ravi A. ; Shen, Victoria ; Bilusic, Marijo ; Schlom, Jeffrey ; Gulley, James L. ; Steinberg, Seth M.

AbstractBackgroundBrachyury 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 MethodsAdults 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.ResultsBetween 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.ConclusionNo 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 PracticeChordoma 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.

01 Nov 2015·Cancer Immunology ResearchQ1 · MEDICINE

Phase I Trial of a Yeast-Based Therapeutic Cancer Vaccine (GI-6301) Targeting the Transcription Factor Brachyury

Q1 · MEDICINE

Article

Author: Madan, Ravi A. ; Arlen, Philip M. ; Heery, Christopher R. ; Marté, Jennifer L. ; Rodell, Timothy C. ; Schlom, Jeffrey ; Dahut, William ; Grenga, Italia ; Gulley, James L. ; Singh, B. Harpreet ; Donahue, Renee N. ; Rauckhorst, Myrna

AbstractThe 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.

100 Deals associated with Brachyury peptide vaccine(GlobeImmune, Inc.)

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R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Germ Cell and Embryonal Neoplasms	Phase 2	-	GlobeImmune, Inc.	-
Melanoma	Preclinical	-	ImmunityBio, Inc.	01 Dec 2017
Merkel Cell Carcinoma	Preclinical	-	ImmunityBio, Inc.	01 Dec 2017
Squamous Cell Carcinoma of Head and Neck	Preclinical	-	ImmunityBio, Inc.	01 Dec 2017
Transitional Cell Carcinoma	Preclinical	-	ImmunityBio, Inc.	01 Dec 2017
Triple Negative Breast Cancer	Preclinical	-	ImmunityBio, Inc.	01 Dec 2017
Squamous Cell Carcinoma	Discovery	US	NantKwest, Inc.	13 Jan 2018
Triple Negative Breast Cancer	Discovery	-	ImmunityBio, Inc.	01 Dec 2017
Chordoma	Discovery	US	ImmunityBio, Inc.	01 May 2015
Chordoma	Discovery	US	National Cancer Institute	01 May 2015

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT03586869 (QUILT-3.080, CTgov)	Phase 1/2	Pancreatic Cancer	3	Avelumab+Aldoxorubicin HCl+GI-6301+GI-4000+ETBX-061+ETBX-051+ETBX-011+fluorouracil+ALT-803+ETBX-021+nab-paclitaxel+Cyclophosphamide+haNK for infusion+Leucovorin+GI-6207+bevacizumab+Oxaliplatin+Capecitabine	pzxbqkzpqy(scqaashtyz) = tscizsracz ewqhjdepxy (opiudqjohe, ykucdklrca - bqthhakxtg) View more	-	27 Aug 2024
NCT03387085 (QUILT-3.067, CTgov)	Phase 1/2	Triple Negative Breast Cancer	9	SBRT+Aldoxorubicin HCl+GI-6301+GI-4000+ETBX-061+ETBX-051+ETBX-011+5-fluorouracil+N-803+nab-paclitaxel+CYCLOPHOSPHAMIDE+Avelumab+haNK for Infusion+Leucovorin+GI-6207+Cisplatin+Bevacizumab+Capecitabine	lkjzlgeewh(cecxbdaovk) = lfgsrkbimc jjunibrnyg (fzoysrbrxd, kjidrppkle - hpcufmzulg) View more	-	09 Aug 2024
NCT03387111 (CTgov)	Phase 1/2	Squamous Cell Carcinoma	4	SBRT+Aldoxorubicin HCl+GI-6301+GI-4000+cetuximab+ETBX-061+ETBX-051+ETBX-011+Necitumumab+fluorouracil+N-803+ETBX-021+nab-paclitaxel+Cyclophosphamide+Avelumab+haNK for infusion+Leucovorin+GI-6207+Cisplatin+Bevacizumab+Capecitabine	bsxfsgdkak(sgwizpwuoe) = flvcxtxvlm qoaumxelrl (mvroegazzn, fanotewoql - crlqdadfka) View more	-	05 Aug 2024
NCT02383498 (QUILT-3.011, CTgov)	Phase 2	Chordoma	24	Radiotherapy+GI-6301 Vaccine (Yeast- Brachyury) (GI-6301 Vaccine)	wwpxbvrpbz(fvilwmfzou) = ouxuiwskkw xpqiaiuzyk (qbbuznhxfa, myknkxdzqy - ycbsilmmwc) View more	-	20 May 2024
NCT02383498 (QUILT-3.011, CTgov)	Phase 2	Chordoma	24	Radiotherapy (Placebo)	wwpxbvrpbz(fvilwmfzou) = brjpweoero xpqiaiuzyk (qbbuznhxfa, cxalklnbhw - ppsbbmoyvc) View more	-	20 May 2024
NCT02383498 (QUILT-3.011, ASCO2020) Manual	Phase 2	Chordoma	22	photon or proton RT+GI-6301	(rjirlxzjbn) = wkmwqppepc amirkwykoh (ihrancowxl ) View more	Negative	29 May 2020
NCT02383498 (QUILT-3.011, ASCO2020) Manual	Phase 2	Chordoma	22	photon or proton RT+placebo	(rjirlxzjbn) = ltoyqkvxwy amirkwykoh (ihrancowxl ) View more	Negative	29 May 2020
NCT01519817 (CTgov)	Phase 1	Adenocarcinoma \| Colonic Cancer	34	Yeast-Brachyury vaccine (4 YU (Dose Level 1))	zmeyeenqxh(jaggynadsf) = ppntksutei ullxahaqai (ydllwaefgp, uqyivlhjrz - nkdpjakjqk) View more	-	31 Jul 2017
NCT01519817 (CTgov)	Phase 1	Adenocarcinoma \| Colonic Cancer	34	Yeast-Brachyury vaccine (16 YU (Dose Level 2))	zmeyeenqxh(jaggynadsf) = vvfrwmgrlw ullxahaqai (ydllwaefgp, lzwcrcxuna - pepgytculq) View more	-	31 Jul 2017
NCT01519817 (ASCO2014)	Phase 1	Chordoma	7	GI-6301 vaccine	flujsvkard(alzdfwumzn) = cbrqvdhyjv uumcengkxd (nymwgefbrm )	-	20 May 2014
NCT01519817 (ASCO2014)	Phase 1	Neoplasms	27	GI-6301 vaccine	obsesazjxx(pvxcjjlfyp) = ksqvyinrsy ahphrzsuvf (wcjhsadhyy ) View more	-	20 May 2014