Pilot Randomized Neo-adjuvant Evaluation of Agonist Anti-CD27 Monoclonal Antibody Varlilumab on Immunologic Activities of IMA950 Vaccine Plus Poly-ICLC in Patients With WHO Grade II Low-Grade Glioma (LGG)

This is a pilot, randomized, two arm neoadjuvant vaccine study in human leukocyte antigen-A2 positive (HLA-A2+) adults with World Health Organization (WHO) grade II glioma, for which surgical resection of the tumor is clinically indicated. Co-primary objectives are to determine: 1) the safety of the novel combination of subcutaneously administered IMA950 peptides and poly-ICLC (Hiltonol) and i.v. administered CDX-1127 (Varlilumab) in the neoadjuvant approach; and 2) whether addition of i.v. CDX-1127 (Varlilumab) increases the response rate and magnitude of CD4+ and CD8+ T-cell responses against the IMA950 peptides in post-vaccine peripheral blood mononuclear cell (PBMC) samples obtained from participating patients.

开始日期2017-04-03

申办/合作机构

The University of California, San Francisco

[+2]

NCT01920191

/ Completed临床1/2期IIT

Phase I/II Study of Intradermal IMA950 Peptide-based Vaccine Adjuvanted With Intra Muscular Poly-ICLC in Combination With Temozolomide in Newly Diagnosed HLA-A2 Glioblastoma Patients

RATIONALE : IMA 950 is multi tumour-associated peptides (TUMAPs) vaccine, these peptides have been identified on primary glioblastoma multiforme (GBM) cells. Poly-ICLC is a potent vaccine adjuvant with broad innate and adaptive immune enhancing effects. IMA 950 and Poly-ICLC will be administered to patients alongside standard primary therapy for glioblastoma. This includes the alkylating drug temozolomide (TMZ). Effective vaccine-induced immune responses associated with prolonged survival have been observed in glioblastoma patients during TMZ adjuvant therapy, suggesting a possible synergistic effect. A second component of glioblastoma standard treatment is external beam irradiation of the tumor site post-surgery. As a side effect, potentially beneficial tumor-infiltrating immune cells may also be killed by radiation. However, the combination of radiation with immunotherapy has been suggested to be favorable both in pre-clinical models.

开始日期2013-08-01

申办/合作机构

Les Hôpitaux Universitaires de Genève

[+2]

NCT01403285

/ Terminated临床1期

A Phase 1 Trial of Peptide-Based Glioma Vaccine IMA950 in Patients With Glioblastoma (GBM)

BACKGROUND: Active immunotherapy of cancer is based on the premise that the vaccine raises a cytotoxic immune response to tumor-associated antigens, thereby destroying malignant cells without harming normal cells.
IMA950 is a therapeutic multi-peptide vaccine containing 11 tumor-associated peptides (TUMAPs) found in a majority of glioblastomas, and is designed to activate TUMAP-specific T cells. The use of 11 TUMAPs increases the likelihood of a multi-clonal, highly specific T-cell response against tumor cells leading to decreased likelihood of immune evasion of the tumor by down-regulation of target antigens.
PURPOSE: The primary objective of this study is to determine the safety and tolerability of IMA950 when given with cyclophosphamide, granulocyte macrophage-colony stimulating factor (GM-CSF) and imiquimod in patients with glioblastoma and to determine if IMA950 shows sufficient immunogenicity in these patients.
ELIGIBILITY: Patients with histologically proven GBMs who have completed radiotherapy, and have stable disease following at least 4 cycles of adjuvant temozolomide.

开始日期2011-08-01

申办/合作机构

Immatics Biotechnologies GmbH

[+1]

100 项与 IMA-950 相关的临床结果

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100 项与 IMA-950 相关的转化医学

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100 项与 IMA-950 相关的专利（医药）

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项与 IMA-950 相关的文献（医药）

2024-02-02·Neuro-Oncology

A combinatory vaccine with IMA950 plus varlilumab promotes effector memory T-cell differentiation in the peripheral blood of patients with low-grade gliomas

Article

作者: Molinaro, Annette M ; Shai, Anny ; Butowski, Nicholas A ; Ogino, Hirokazu ; Hilf, Norbert ; Watchmaker, Payal B ; Daras, Mariza ; Oberheim Bush, Nancy Ann ; Wang, Albert S ; Hervey-Jumper, Shawn L ; Okada, Hideho ; Taylor, Jennie W ; Rabbitt, Jane E ; Chang, Susan M ; Keler, Tibor ; Okada, Kaori ; Mayer-Mokler, Andrea ; Shahin, Maryam ; Phillips, Joanna J ; Gibson, David ; Tedesco, Meghan R ; Salazar, Andres M ; Berger, Mitchel S ; Perry, Arie ; Clarke, Jennifer L ; Saijo, Atsuro

AbstractBackgroundCentral nervous system (CNS) WHO grade 2 low-grade glioma (LGG) patients are at high risk for recurrence and with unfavorable long-term prognosis due to the treatment resistance and malignant transformation to high-grade glioma. Considering the relatively intact systemic immunity and slow-growing nature, immunotherapy may offer an effective treatment option for LGG patients.MethodsWe conducted a prospective, randomized pilot study to evaluate the safety and immunological response of the multipeptide IMA950 vaccine with agonistic anti-CD27 antibody, varlilumab, in CNS WHO grade 2 LGG patients. Patients were randomized to receive combination therapy with IMA950 + poly-ICLC and varlilumab (Arm 1) or IMA950 + poly-ICLC (Arm 2) before surgery, followed by adjuvant vaccines.ResultsA total of 14 eligible patients were enrolled in the study. Four patients received pre-surgery vaccines but were excluded from postsurgery vaccines due to the high-grade diagnosis of the resected tumor. No regimen-limiting toxicity was observed. All patients demonstrated a significant increase of anti-IMA950 CD8+ T-cell response postvaccine in the peripheral blood, but no IMA950-reactive CD8+ T cells were detected in the resected tumor. Mass cytometry analyses revealed that adding varlilumab promoted T helper type 1 effector memory CD4+ and effector memory CD8+ T-cell differentiation in the PBMC but not in the tumor microenvironment.ConclusionThe combinational immunotherapy, including varlilumab, was well-tolerated and induced vaccine-reactive T-cell expansion in the peripheral blood but without a detectable response in the tumor. Further developments of strategies to overcome the blood-tumor barrier are warranted to improve the efficacy of immunotherapy for LGG patients.

2024-01-01·International Journal of Biological Sciences

The role of TNC in atherosclerosis and drug development opportunities

Review

作者: Yan, Saisai ; Zhang, Tingting ; Peng, Xiaojin ; Xing, Jiyao ; Wang, Yanhong ; Xu, Jiazhen ; Shao, Yingchun ; Zhang, Renshuai ; Zhang, Daijun ; Li, Qian ; Chen, Wujun ; Ren, Chunling ; Wang, Chao ; Xing, Dongming ; Yu, Sha

Tenascin C (TNC), a rich glycoprotein of the extracellular matrix, exhibits a pro-atherosclerosis or anti-atherosclerosis effect depending on its location. TNC, especially its C domain/isoform (TNC-C), is strongly overexpressed in atherosclerotic plaque active areas but virtually undetectable in most normal adult tissues, suggesting that TNC is a promising delivery vector target for atherosclerosis-targeted drugs. Many delivery vectors were investigated by recognizing TNC-C, including G11, G11-iRGD, TN11, PL1, and PL3. F16 and FNLM were also investigated by recognizing TNC-A1 and TNC, respectively. Notably, iRGD was undergoing clinical trials. PL1 not only recognizes TNC-C but also the extra domain-B (EDB) of fibronectin (FN), which is also a promising delivery vector for atherosclerosis-targeted drugs, and several conjugate agents are undergoing clinical trials. The F16-conjugate agent F16IL2 is undergoing clinical trials. Therefore, G11-iRGD, PL1, and F16 have great development value. Furthermore, ATN-RNA and IMA950 were investigated in clinical trials as therapeutic drugs and vaccines by targeting TNC, respectively. Therefore, targeting TNC could greatly improve the success rate of atherosclerosis-targeted drugs and/or specific drug development. This review discussed the role of TNC in atherosclerosis, atherosclerosis-targeted drug delivery vectors, and agent development to provide knowledge for drug development targeting TNC.

2019-07-11·Neuro-Oncology1区 · 医学

Phase I/II trial testing safety and immunogenicity of the multipeptide IMA950/poly-ICLC vaccine in newly diagnosed adult malignant astrocytoma patients

1区 · 医学

Article

作者: Kreutzfeldt, Mario ; Corlazzoli, Francesca ; Momjian, Shahan ; Grandjean Hallez, Nicole ; Merkler, Doron ; Dietrich, Pierre-Yves ; Philippin, Géraldine ; Dutoit, Valérie ; Lobrinus, Alexander ; Koka, Avinash ; Marinari, Eliana ; Migliorini, Denis ; Hottinger, Andreas ; Gustave, Robin ; Walker, Paul R ; Patrikidou, Anna ; Vargas, Maria-Isabel ; Blazek, Nathalie ; Wasem, Joëlle ; Allard, Mathilde ; Widmer, Valérie

AbstractBackgroundPeptide vaccines offer the opportunity to elicit glioma-specific T cells with tumor killing ability. Using antigens eluted from the surface of glioblastoma samples, we designed a phase I/II study to test safety and immunogenicity of the IMA950 multipeptide vaccine adjuvanted with poly-ICLC (polyinosinic-polycytidylic acid stabilized with polylysine and carboxymethylcellulose) in human leukocyte antigen A2+ glioma patients.MethodsAdult patients with newly diagnosed glioblastoma (n = 16) and grade III astrocytoma (n = 3) were treated with radiochemotherapy followed by IMA950/poly-ICLC vaccination. The first 6 patients received IMA950 (9 major histocompatibility complex [MHC] class I and 2 MHC class II peptides) intradermally and poly-ICLC intramuscularly (i.m.). After protocol amendment, IMA950 and poly-ICLC were mixed and injected subcutaneously (n = 7) or i.m. (n = 6). Primary endpoints were safety and immunogenicity. Secondary endpoints were overall survival, progression-free survival at 6 and 9 months, and vaccine-specific peripheral cluster of differentiation (CD)4 and CD8 T-cell responses.ResultsThe IMA950/poly-ICLC vaccine was safe and well tolerated. Four patients presented cerebral edema with rapid recovery. For the first 6 patients, vaccine-induced CD8 T-cell responses were restricted to a single peptide and CD4 responses were absent. After optimization of vaccine formulation, we observed multipeptide CD8 and sustained T helper 1 CD4 T-cell responses. For the entire cohort, CD8 T-cell responses to a single or multiple peptides were observed in 63.2% and 36.8% of patients, respectively. Median overall survival was 19 months for glioblastoma patients.ConclusionWe provide, in a clinical trial, using cell surface-presented antigens, insights into optimization of vaccines generating effector T cells for glioma patients.Trial registrationClinicaltrials.gov NCT01920191.

100 项与 IMA-950 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
胶质母细胞瘤	临床2期	-	Immatics Biotechnologies GmbH	-
胶质母细胞瘤	临床2期	-	Cancer Research UK	-
多形性胶质母细胞瘤	药物发现	英国	Immatics Biotechnologies GmbH	2010-07-01

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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


NCT02924038 (CTgov)	临床1期	混合型少突星形细胞瘤 \| 弥漫性星形细胞瘤 \| 胶质瘤 \| 少突神经胶质瘤 \| WHO II级胶质瘤 \| 高级别胶质瘤 \| 低级神经胶质瘤	14	poly-ICLC+Varlilumab+IMA950 (IMA950/Poly-ICLC Subcutaneous (subQ) + Varlilumab IV)	鹽艱顧遞選鑰鏇獵糧網(餘艱蓋鏇選衊餘築構製) = 襯鑰夢積遞蓋醖齋築選顧餘顧構簾齋顧積積鏇 (積憲夢築積糧鹹鹽製襯, 製夢艱簾構積齋艱鬱淵 ~ 鑰襯顧積鏇鹹憲糧淵鏇) 更多	-	2024-06-14
				poly-ICLC+IMA950 (IMA950/Poly-ICLC subQ Only)	鹽艱顧遞選鑰鏇獵糧網(餘艱蓋鏇選衊餘築構製) = 觸膚獵範鬱廠廠遞憲範顧餘顧構簾齋顧積積鏇 (積憲夢築積糧鹹鹽製襯, 壓鑰鹽鏇繭壓衊積觸廠 ~ 餘壓襯衊願鬱糧衊膚鹽) 更多