TT-10x(TT-10x) - 药物靶点：EBNA1 x LMP1 x BARF1蛋白_在研适应症：EBV相关淋巴瘤，霍奇金淋巴瘤，鼻咽癌_专利_临床

概要

基本信息

药物类型

T细胞疗法

别名

Autologous EBV specific Cytotoxic T cells (Tessa Therapeutics)、MABEL CTLs (Tessa Therapeutics)、TT-10X

靶点

EBNA1 x LMP1 x BARF1蛋白

作用机制

EBNA1调节剂(EB病毒核抗原-1调节剂)、潜伏膜蛋白1调节剂、BARF1蛋白调节剂

治疗领域

肿瘤口颌疾病耳鼻咽喉疾病+ [3]

在研适应症

EBV相关淋巴瘤霍奇金淋巴瘤鼻咽癌+ [2]

非在研适应症

晚期鼻咽癌复发性经典霍奇金淋巴瘤

原研机构

Baylor College of Medicine

在研机构

Baylor College of Medicine

非在研机构

Tessa Therapeutics Ltd

最高研发阶段临床1期

首次获批日期-

最高研发阶段(中国)-

特殊审评-

登录后查看时间轴

关联

3

项与 TT-10x 相关的临床试验

NCT02287311

/ Active, not recruiting临床1期IIT

ADMINISTRATION OF MOST CLOSELY MATCHED THIRD PARTY RAPIDLY GENERATED LMP, BARF1 and EBNA1 SPECIFIC CYTOTOXIC T-LYMPHOCYTES TO PATIENTS WITH EBV-POSITIVE LYMPHOMA AND OTHER EBV-POSITIVE MALIGNANCIES

The subject has a type of cancer or lymph gland disease associated with a virus called Epstein Barr Virus (EBV), which has come back, is at risk of coming back, or has not gone away after standard treatments. This research study uses special immune system cells called LMP, BARF-1 and EBNA1- specific cytotoxic T lymphocytes (MABEL CTLs).
Some patients with Lymphoma (such as Hodgkin (HD) or non-Hodgkin Lymphoma (NHL)), T/NK-lymphoproliferative disease, or CAEBV, or solid tumors such as nasopharyngeal carcinoma (NPC), smooth muscle tumors, and leiomyosarcomas show signs of a virus called EBV before or at the time of their diagnosis. EBV causes mononucleosis or glandular fever ("mono" or the "kissing disease"). EBV is found in the cancer cells of up to half the patients with HD and NHL, suggesting that it may play a role in causing Lymphoma. The cancer cells (in lymphoma) and some immune system cells (in CAEBV) infected by EBV are able to hide from the body's immune system and escape destruction. EBV is also found in the majority of NPC and smooth muscle tumors, and some leiomyosarcomas. We want to see if special white blood cells (MABEL CTLs) that have been trained to kill EBV infected cells can survive in your blood and affect the tumor.
In previous studies, EBV CTLs were generated from the blood of the patient, which was often difficult if the patient had recently received chemotherapy. Also, it took up to 1-2 months to make the cells, which is not practical when a patient needs more urgent treatment. To address these issues, the MABEL CTLs were made in the lab in a simpler, faster, and safer way. The MABEL CTLs will still see LMP proteins but also two other EBV proteins called EBNA-1 and BARF. To ensure these cells are available for use in patients in urgent clinical need, we have generated MABEL CTLs from the blood of healthy donors and created a bank of these cells, which are frozen until ready for use. We have previously successfully used frozen T cells from healthy donors to treat EBV lymphoma and virus infections and we now have improved our production method to make it faster.
In this study, we want to find out if we can use banked MABEL CTLs to treat HD, NHL, T/NK-lymphoproliferative disease, CAEBV, NPC, smooth muscle tumors or leiomyosarcoma. We will search the bank to find a MABEL CTL line that is a partial match with the subject.
MABEL CTLs are investigational and not approved by the Food and Drug Administration.

开始日期2015-02-01

申办/合作机构

Baylor College of Medicine

[+2]

NCT02578641

/ Completed临床3期

A Multicentre, Randomized, Open-Label, Phase III Clinical Trial Of Gemcitabine And Carboplatin Followed By Epstein-Barr Virus-Specific Autologous Cytotoxic T Lymphocytes Versus Gemcitabine And Carboplatin As First Line Treatment For Advanced Nasopharyngeal Carcinoma(NPC) Patients

This study is a multi-center, randomized, open label, Phase III clinical trial for advanced Nasopharyngeal Carcinoma(NPC) Patients.
Drugs used in chemotherapy, such as gemcitabine and carboplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving an infusion of a person's cytotoxic T cells (CTL) that have been treated in the laboratory may help the body build an effective immune response to kill tumor cells. Giving combination chemotherapy together with laboratory-treated T cells may kill more tumor cells. This Phase III trial is to assess if combined gemcitabine-carboplatin (GC) followed by adoptive T-cell therapy would improve clinical outcome for patients with advanced nasopharyngeal carcinoma (NPC). It is also the world's first, and largest, Phase 3 T-cell therapy cancer trial ever conducted, and enrollment is ongoing for 330 patients from 30 hospital centers across Asia and the United States.
This clinical trial is conducted on the back of a successful Phase 2 NPC trial involving 38 patients at the National Cancer Centre, Singapore. This trial produced the best published 2-year (62.9%), and median overall survival (OS) data (29.9 months) in 35 patients with advanced NPC who received autologous EBV-specific CTL. Kindly see https://www-ncbi-nlm-nih-gov.libproxy1.nus.edu.sg/pmc/articles/PMC3978790/ for the Phase 2 publication titled "Adoptive T-cell Transfer and Chemotherapy in the First line treatment of Metastatic and/or Locally Recurrent Nasopharyngeal Carcinoma".

开始日期2014-07-01

申办/合作机构

Tessa Therapeutics Ltd

NCT00058773

/ Terminated临床1期IIT

Administration of Autologous Neomycin Resistant Gene Marked EBV Specific Cytotoxic T-Lymphocytes as Therapy for Patients Receiving Autologous Bone Marrow Transplant for Relapsed EBV-Positive Lymphoma.

Subjects have a type of lymph gland cancer called Hodgkin or non-Hodgkin Lymphoma, which has come back or not gone away after treatment, including the best treatment we know for relapsed Lymphoma. We are asking subjects to volunteer to be in a research study using Epstein Barr virus (EBV) specific cytotoxic T lymphocytes, a new experimental therapy. This therapy has never been used in patients with Hodgkin disease or this type of non-Hodgkin Lymphoma but it has been used successfully in children with other types of blood cancer caused by EBV after bone marrow transplantation.
Some patients with Hodgkin disease or non-Hodgkin Lymphoma show evidence of infection with the virus that causes infectious mononucleosis Epstein Barr virus (EBV) before or at the time of their diagnosis of Lymphoma. EBV is often found in the cancer cells suggesting that it may play a role in causing Lymphoma. The cancer cells infected by EBV are very clever because they are able to hide from the body's immune system and escape destruction. We want to see if we can grow special white blood cells, called T cells, that have been trained to kill EBV infected cells and give them back to subjects.

开始日期1996-01-01

申办/合作机构

Baylor College of Medicine

[+2]

100 项与 TT-10x 相关的临床结果

登录后查看更多信息

100 项与 TT-10x 相关的转化医学

登录后查看更多信息

100 项与 TT-10x 相关的专利（医药）

登录后查看更多信息

26

项与 TT-10x 相关的文献（医药）

2025-01-01·CLINICAL PHARMACOLOGY & THERAPEUTICS

An Innovative Approach to Optimize First‐In‐Human Minimal Anticipated Biological Effect Level Based Starting Dose in Oncology Trials for Bispecific T‐Cell Engagers: Experience from A Solid Tumor Bispecific T‐Cell Engager

Article

作者: Stienen, Sabine ; Rattel, Benno ; Bailis, Julie ; Lutteropp, Michael ; Townsley, Danielle ; Mehta, Khamir ; Friedrich, Matthias ; Sternjak, Alexander ; Zhou, Di ; Kischel, Roman ; Upreti, Vijay V.

Bispecific T‐cell engagers (Bi‐TCEs) have revolutionized the treatment and management of both hematological and solid tumor indications with opportunities to become best‐in‐class therapeutics for cancer. However, defining the dose and dosing regimen for the first‐in‐human (FIH) studies of Bi‐TCEs can be challenging, as a high starting dose can expose subjects to serious toxicity while a low starting dose based on traditional minimal anticipated biological effect level (MABEL) approach could lead to lengthy dose escalations that exposes seriously ill patients to sub‐therapeutic dosing. Leveraging our in‐depth and broad clinical development experience across three generations of Bi‐TCEs across both liquid and solid tumor indications, we developed an innovative modified MABEL approach for starting dose selection that integrates knowledge based on the target biology, indication, toxicology, in vitro, in vivo pharmacological evaluations, and translational pharmacokinetic/pharmacodynamic (PK/PD) modeling, together with anticipated safety profile. Compared to the traditional MABEL approach in which high effector to target (E:T) cell ratios are typically used, our innovative approach utilized an optimized E:T cell ratio that better reflects the tumor microenvironment. This modified MABEL approach was successfully applied to FIH dose selection for a half‐life extended (HLE) Bi‐TCE for gastric cancer. This modified MABEL approach enabled a 10‐fold higher starting dose that was deemed safe and well tolerated and saved at least two dose‐escalation cohorts before reaching the projected efficacious dose. This approach was successfully accepted by global regulatory agencies and can be applied for Bi‐TCEs across both hematological and solid tumor indications for accelerating the clinical development for Bi‐TCEs.

2024-12-01·ANNALS OF ONCOLOGY

Gemcitabine, carboplatin, and Epstein–Barr virus-specific autologous cytotoxic T lymphocytes for recurrent or metastatic nasopharyngeal carcinoma: VANCE, an international randomized phase III trial

Article

作者: Hasbullah, H.H. ; Wirasorn, K ; Lulla, P. ; Brenner, M.K. ; Sirachainan, E ; Samol, J. ; Ding, C. ; Horak, I ; Ang, M K ; Algazi, A ; Ho, G F ; Wang, H.-M. ; Liu, Y C ; Toh, H C ; Ho, K F ; Myo, A. ; Toh, H.C. ; Wang, W.-W. ; Yang, M-H ; Wirasorn, K. ; Lertbutsayanukul, C. ; Ho, G.F. ; Ho, K.F. ; Wirth, L J ; Low, S.H.J. ; Tan, S H ; Tho, L M ; Nadler, E ; Wang, H-M ; Ding, C ; Low, S H J ; Colevas, A.D. ; Hong, R.-L. ; Ang, S F ; Nadler, E. ; Chitapanarux, I. ; Chitapanarux, I ; Brenner, M K ; Tho, L.M. ; Ang, S.F. ; Tan, S.H. ; Hsieh, C Y ; Lulla, P ; Liu, Y.C. ; Myo, A ; Ong, W S ; Ang, M.K. ; Hsieh, C.Y. ; Lertbutsayanukul, C ; Sirachainan, E. ; Yang, M.-H. ; Colevas, A D ; Samol, J ; Hong, R-L ; Wang, W-W ; Wirth, L.J. ; Ong, W.S. ; Horak, I. ; Algazi, A. ; Hasbullah, H H

BACKGROUND:

Epstein-Barr virus-specific cytotoxic T lymphocyte (EBV-CTL) is an autologous adoptive T-cell immunotherapy generated from the blood of individuals and manufactured without genetic modification. In a previous phase II trial of locally recurrent or metastatic nasopharyngeal carcinoma (R/M NPC) patients, first-line gemcitabine and carboplatin (GC) and EBV-CTL combination demonstrated objective antitumor EBV-CTL activity and a favorable safety profile. The present study explored whether this combined first-line chemo-immunotherapy strategy would produce superior clinical efficacy and better quality of life compared with conventional chemotherapy treatment.

PATIENTS AND METHODS:

This multicenter, randomized, phase III trial evaluated the efficacy and safety of GC followed by EBV-CTL versus GC alone as first-line treatment of R/M NPC patients. Thirty clinical sites in Singapore, Malaysia, Taiwan, Thailand, and the USA were included. Subjects were randomized to first-line GC (four cycles) and EBV-CTL (six cycles) or GC (six cycles) in a 1 : 1 ratio. The primary outcome was overall survival (OS) and secondary outcomes included progression-free survival, objective response rate, clinical benefit rate, quality of life, and safety.

CLINICALTRIALS:

gov identifier: NCT02578641.

RESULTS:

A total of 330 subjects with NPC were enrolled. Most subjects in both treatment arms received four or more cycles of chemotherapy and most subjects in the GC + EBV-CTL group received two or more infusions of EBV-CTL. The central Good Manufacturing Practices (GMP) facility produced sufficient EBV-CTL for 94% of GC + EBV-CTL subjects. The median OS was 25.0 months in the GC + EBV-CTL group and 24.9 months in the GC group (hazard ratio = 1.19; 95% confidence interval 0.91-1.56; P = 0.194). Only one subject experienced a grade 2 serious adverse event related to EBV-CTL.

CONCLUSIONS:

GC + EBV-CTL in subjects with R/M NPC demonstrated a favorable safety profile but no overall improvement in OS versus chemotherapy. This is the largest adoptive T-cell therapy trial reported in solid tumors to date.

2022-09-01·CTS-Clinical and Translational Science

Model‐informed drug development for immuno‐oncology agonistic anti‐GITR antibody GWN323: Dose selection based on MABEL and biologically active dose

Article

作者: Wolf, Babette ; Dang, Anhthu ; Knee, Deborah ; Ji, Yan ; Sy, Sherwin K. B. ; Chen, Xinhui ; Mataraza, Jennifer

Abstract:

GWN323, an agonistic human anti‐GITR (glucocorticoid‐induced TNFR‐related protein) IgG1 antibody, was studied clinically as an immuno‐oncology therapeutic agent. A model‐based minimum anticipated biological effect level (MABEL) approach integrating in vitro and in vivo data informed dose selection for the first‐in‐human (FIH) study. Data evaluated included pharmacokinetics (PK) of DTA‐1.mIgG2a (mouse surrogate GITR antibody for GWN323), target‐engagement pharmacodynamic (PD) marker soluble GITR (sGITR), tumor shrinkage in Colon26 syngeneic mice administered with DTA‐1.mIgG2a, cytokine release of GWN323 in human peripheral blood mononuclear cells, and GITR binding affinity. A PK model was developed to describe DTA‐1.mIgG2a PK, and its relationship with sGITR was also modeled. Human GWN323 PK was predicted by allometric scaling of mouse PK. Based on the totality of PK/PD modeling and in vitro and in vivo pharmacology and toxicology data, MABEL was estimated to be 3–10 mg once every 3 weeks (Q3W), which informed the starting dose selection of the FIH study. Based on tumor kinetic PK/PD modeling of tumor inhibition by DTA‐1.mIgG2a in Colon26 mice and the predicted human PK of GWN323, the biologically active dose of GWN323 was predicted to be 350 mg Q3W, which informed the dose escalation of the FIH study. GWN323 PK from the FIH study was described by a population PK model; the relationship with ex vivo interleukin‐2 release, a target‐engagement marker, was also modeled. The clinical PK/PD modeling data supported the biological active dose projected from the translational PK/PD modeling in a “learn and confirm” paradigm of model‐informed drug development of GWN323.

100 项与 TT-10x 相关的药物交易

登录后查看更多信息

研发状态

10 条进展最快的记录,

登录

后查看更多信息

适应症	最高研发状态	国家/地区	公司	日期
晚期鼻咽癌	临床3期	美国	Tessa Therapeutics Ltd	2014-07-01
晚期鼻咽癌	临床3期	马来西亚	Tessa Therapeutics Ltd	2014-07-01
晚期鼻咽癌	临床3期	新加坡	Tessa Therapeutics Ltd	2014-07-01
晚期鼻咽癌	临床3期	中国台湾	Tessa Therapeutics Ltd	2014-07-01
晚期鼻咽癌	临床3期	泰国	Tessa Therapeutics Ltd	2014-07-01
鼻咽癌	临床3期	美国	Tessa Therapeutics Ltd	2014-07-01
鼻咽癌	临床3期	马来西亚	Tessa Therapeutics Ltd	2014-07-01
鼻咽癌	临床3期	新加坡	Tessa Therapeutics Ltd	2014-07-01
鼻咽癌	临床3期	中国台湾	Tessa Therapeutics Ltd	2014-07-01
鼻咽癌	临床3期	泰国	Tessa Therapeutics Ltd	2014-07-01

登录后查看更多信息

临床结果

适应症

分期

评价

查看全部结果

研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


NCT02578641 (VANCE, Pubmed \| Ann Oncol) 人工标引	临床3期	鼻咽癌一线	330	Gemcitabine ancarboplatinin EBV-CTLEBV-CTL	範糧廠衊淵願艱衊窪壓(餘鹹願積構膚遞餘鑰窪) = 蓋壓鹽鬱遞積鹹鑰襯願憲夢獵獵簾簾夢觸鏇製 (廠齋獵醖願廠膚壓網範 )	不佳	2024-09-01
				Gemcitabine carboplatinatin (GC)	範糧廠衊淵願艱衊窪壓(餘鹹願積構膚遞餘鑰窪) = 鑰夢觸夢簾積壓襯壓鑰憲夢獵獵簾簾夢觸鏇製 (廠齋獵醖願廠膚壓網範 )
NCT02578641 (VANCE, CTgov)	临床3期	鼻咽癌 \| 晚期鼻咽癌	330	carboplatin+gemcitabine (Chemo + EBV-CTL)	鹹蓋齋醖鏇壓餘選觸簾(繭醖餘襯壓願築廠鏇簾) = 鑰鑰鹹夢築鏇鏇獵鬱願艱築鑰鬱醖壓築鹽製網 (遞窪願觸憲鏇廠憲衊醖, 鬱衊築膚鬱壓網鏇蓋築 ~ 網築襯齋齋築蓋淵獵構) 更多	-	2023-06-28
				carboplatin+gemcitabine (Chemo Only)	鹹蓋齋醖鏇壓餘選觸簾(繭醖餘襯壓願築廠鏇簾) = 鹽餘糧繭積壓繭鹽齋餘艱築鑰鬱醖壓築鹽製網 (遞窪願觸憲鏇廠憲衊醖, 網構積網築鹹顧築積積 ~ 襯範齋艱製廠餘遞鏇鹽) 更多
Tandem Meetings ASTCT and CIBMTR2008	N/A	爱泼斯坦-巴尔病毒相关鼻咽癌	-	Adoptively Transferred Cytotoxic T Lymphocytes (EBV-specific CTL)	憲遞願蓋網簾醖廠構鑰(築製廠簾襯選淵襯願製) = Transient swelling at known disease sites in 4 patients 構鑰鹽範窪糧範鬱網鹹 (構淵範膚鏇夢憲鏇觸構 )	-	2008-02-01
				Adoptively Transferred Cytotoxic T Lymphocytes (CD45 MAbs)