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 ; Saijo, Atsuro ; Clarke, Jennifer L

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.

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 ; Dietrich, Pierre-Yves ; Philippin, Géraldine ; Grandjean Hallez, Nicole ; Merkler, Doron ; 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.

2018-02-01·OncoImmunology2区 · 医学

Antigenic expression and spontaneous immune responses support the use of a selected peptide set from the IMA950 glioblastoma vaccine for immunotherapy of grade II and III glioma

2区 · 医学

ArticleOA

作者: Herold-Mende, Christel ; Widmer, Valérie ; Lobrinus, Johannes Alexander ; Walker, Paul R. ; Migliorini, Denis ; Momjian, Shahan ; Okada, Hideho ; Dietrich, Pierre-Yves ; Ranzanici, Giulia ; Dutoit, Valérie ; Costello, Joseph ; Marinari, Eliana ; Weinschenk, Toni

Gliomas are lethal brain tumors that resist standard therapeutic approaches. Immunotherapy is a promising alternative strategy mostly developed in the context of glioblastoma. However, there is a need for implementing immunotherapy for grade II/III gliomas, as these are the most common CNS tumors in young adults with a high propensity for recurrence, making them lethal despite current treatments. We recently identified HLA-A2-restricted tumor-associated antigens by peptide elution from glioblastoma and formulated a multipeptide vaccine (IMA950) evaluated in phase I/II clinical trials with promising results. Here, we investigated expression of the IMA950 antigens in patients with grade II/III astrocytoma, oligodendroglioma or ependymoma, at the mRNA, protein and peptide levels. We report that the BCAN, CSPG4, IGF2BP3, PTPRZ1 and TNC proteins are significantly over-expressed at the mRNA (n = 159) and protein (n = 36) levels in grade II/III glioma patients as compared to non-tumor samples (IGF2BP3 being absent from oligodendroglioma). Most importantly, we detected spontaneous antigen-specific T cell responses to one or more of the IMA950 antigens in 100% and 71% of grade II and grade III patients, respectively (27 patients tested). These patients displayed T cell responses of better quality (higher frequency, broader epitope targeting) than patients with glioblastoma. Detection of spontaneous T cell responses to the IMA950 antigens shows that these antigens are relevant for tumor targeting, which will be best achieved by combination with CD4 epitopes such as the IDH1R132H peptide. Altogether, we provide the rationale for using a selective set of IMA950 peptides for vaccination of patients with grade II/III glioma.

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	临床1期	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 \| 胶质瘤 \| 少突神经胶质瘤 \| WHO II级胶质瘤	14	poly-ICLC+Varlilumab+IMA950 (IMA950/Poly-ICLC Subcutaneous (subQ) + Varlilumab IV)	艱壓觸鏇蓋蓋鬱鬱繭糧(襯網壓憲夢艱膚選膚鹹) = 築簾簾構壓淵鑰膚觸襯獵鬱築鏇蓋製鹹窪艱築 (壓齋築夢壓齋簾膚顧獵, 醖艱鬱艱願淵積遞憲壓 ~ 積齋襯窪製膚選鹹壓窪) 更多	-	2024-06-14
				poly-ICLC+IMA950 (IMA950/Poly-ICLC subQ Only)	艱壓觸鏇蓋蓋鬱鬱繭糧(襯網壓憲夢艱膚選膚鹹) = 顧觸選蓋觸積鹽構鑰齋獵鬱築鏇蓋製鹹窪艱築 (壓齋築夢壓齋簾膚顧獵, 觸顧願願鑰繭窪觸鹽廠 ~ 廠餘範獵壓構選膚餘獵) 更多