This study is being done to evaluate the safety and the clinical activity of MAGE-A3 Antigen-Specific Cancer Immunotherapeutic in patients with unresectable and progressive metastatic cutaneous melanoma.

开始日期2008-09-29

申办/合作机构

GSK Plc

100 项与 Recombinant MAGE-A3 protein immunotherapy(GlaxoSmithKline Plc) 相关的临床结果

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100 项与 Recombinant MAGE-A3 protein immunotherapy(GlaxoSmithKline Plc) 相关的转化医学

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100 项与 Recombinant MAGE-A3 protein immunotherapy(GlaxoSmithKline Plc) 相关的专利（医药）

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项与 Recombinant MAGE-A3 protein immunotherapy(GlaxoSmithKline Plc) 相关的文献（医药）

2021-08-01·Cancer Immunology, Immunotherapy2区 · 医学

Characterization and comparison of innate and adaptive immune responses at vaccine sites in melanoma vaccine clinical trials

2区 · 医学

Article

作者: Deacon, Donna H ; Koeppel, Alexander F ; Slingluff, Craig L ; Meneveau, Max O ; Pollack, Karlyn E ; Turner, Stephen D ; Petroni, Gina R ; Hickman, Alexandra ; Sol-Church, Katia ; Melssen, Marit M ; Smolkin, Mark E ; Pinczewski, Joel

The strength and durability of systemic anti-tumor immune responses induced by cancer vaccines depends on adjuvants to support an immunogenic vaccine site microenvironment (VSME). Adjuvants include water-in-oil emulsions with incomplete Freund's adjuvant (IFA) and combinations of toll-like receptor (TLR) agonists, including a preparation containing TLR4 and TLR9 agonists with QS-21 (AS15). IFA-containing vaccines can promote immune cell accumulation at the VSME, whereas effects of AS15 are largely unexplored. Therefore, we assessed innate and adaptive immune cell accumulation and gene expression at the VSME after vaccination with AS15 and compared to effects with IFA. We hypothesized that AS15 would promote less accumulation of innate and adaptive immune cells at the VSME than IFA vaccines. In two clinical trials, patients with resected high-risk melanoma received either a multipeptide vaccine with IFA or a recombinant MAGE-A3 protein vaccine with AS15. Vaccine site biopsies were obtained after one or multiple vaccines. T cells accumulated early after vaccines with AS15, but this was not durable or of the same magnitude as vaccination in IFA. Vaccines with AS15 increased durable expression of DC- and T cell-related genes, as well as PD-L1 and IDO1, suggesting complex activation and regulation of innate and adaptive immune function with AS15. These changes were generally greater with vaccines containing IFA, but IFA induced reduction in myeloid suppressor cells markers. Evidence of tertiary lymphoid structure (TLS) formation was observed with both adjuvants. Our findings highlight adjuvant-dependent changes in immune features at the VSME that may impact systemic immune responses.

2018-12-01·BMC Cancer2区 · 医学

A phase II trial of recombinant MAGE-A3 protein with immunostimulant AS15 in combination with high-dose Interleukin-2 (HDIL2) induction therapy in metastatic melanoma

2区 · 医学

ArticleOA

作者: Vence, Luis M ; McQuade, Jennifer L ; Torres-Cabala, Carlos A ; James, Marihella L ; Hwu, Wen-Jen ; Bassett, Roland ; Homsi, Jade ; Popuri, Rashmi Murthy

BACKGROUNDHDIL-2 is approved for advanced melanoma based on its durable antitumor activity. MAGE-A3 cancer immunotherapeutic (MAGE-A3 CI) is a recombinant MAGE-A3 protein combined with an immunostimulant adjuvant system and has shown antitumor activity in melanoma. We assessed the safety and anti-tumor activity of HDIL-2 combined with MAGE-A3 CI in advanced melanoma.METHODSPatients with unresectable Stage III or Stage IV MAGE-A3-positive melanoma were enrolled in this phase II study. Treatment included an induction phase of MAGE-A3 CI plus HDIL-2 for 8 cycles followed by a maintenance phase of MAGE-A3 CI monotherapy. The primary endpoints were safety and objective response assessed per RECIST v1.1. Immune biomarker and correlative studies on tumor and peripheral blood were performed.RESULTSEighteen patients were enrolled. Seventeen patients were evaluable for safety and sixteen for response. Responses occurred in 4/16 (25%) patients with 3 complete responses, and stable disease in 6/16 (38%) patients with a disease control rate of 63%. The median duration of response was not reached at median follow-up of 36.8 months. Induction therapy of HDIL-2 + MAGE-A3 CI had similar toxicities to those reported with HDIL-2 alone. Maintenance MAGE-A3 monotherapy was well-tolerated. Increased immune checkpoint receptor expression by circulating T regulatory cells was associated with poor clinical outcomes; and responders tended to have increased tumor infiltrating T cells in the baseline tumor samples.CONCLUSIONSThe safety profile of HDIL-2 + MAGE-A3 CI was similar to HDIL-2 monotherapy. Maintenance MAGE-A3 CI provides robust anti-tumor activity in patients who achieved disease control with induction therapy. Immune monitoring data suggest that MAGE-A3 CI plus checkpoint inhibitors could be a promising treatment for MAGE-A3-positive melanoma.TRIAL REGISTRATIONClinicalTrials.gov, NCT01266603 . Registered 12/24/2010, https://clinicaltrials.gov/ct2/show/NCT01266603.

2018-07-01·The Lancet Oncology1区 · 医学

MAGE-A3 immunotherapeutic as adjuvant therapy for patients with resected, MAGE-A3-positive, stage III melanoma (DERMA): a double-blind, randomised, placebo-controlled, phase 3 trial

1区 · 医学

Article

作者: Thomas Jouary ; John F Thompson ; Bart Spiessens ; Andrea Callegaro ; Wim H J Kruit ; Bernard Guillot ; John A Thompson ; Gabriela Cinat ; Jean-Jacques Grob ; Ralf Gutzmer ; Bernard Mark Smithers ; Muriel Debois ; Vincent G Brichard ; Alessandro Testori ; Kamil Drucis ; Fernando Ulloa-Montoya ; Robert Conry ; Jamila Louahed ; Laurent Machet ; Piotr Rutkowski ; Jaroslaw Jaroszek ; Lev Demidov ; Peter Hersey ; Mario Santinami ; Patrick Therasse ; Benjamin Dizier ; Jelle J Goeman ; Brigitte Dreno ; Sergii Korovin ; Channa Debruyne ; Igor Bondarenko ; Evgeny Levchenko ; Hans C van Houwelingen ; Ivana Krajsova ; John M Kirkwood ; Axel Hauschild ; Susana Puig ; Florent Grange

BACKGROUNDDespite newly approved treatments, metastatic melanoma remains a life-threatening condition. We aimed to evaluate the efficacy of the MAGE-A3 immunotherapeutic in patients with stage IIIB or IIIC melanoma in the adjuvant setting.METHODSDERMA was a phase 3, double-blind, randomised, placebo-controlled trial done in 31 countries and 263 centres. Eligible patients were 18 years or older and had histologically proven, completely resected, stage IIIB or IIIC, MAGE-A3-positive cutaneous melanoma with macroscopic lymph node involvement and an Eastern Cooperative Oncology Group performance score of 0 or 1. Randomisation and treatment allocation at the investigator sites were done centrally via the internet. We randomly assigned patients (2:1) to receive up to 13 intramuscular injections of recombinant MAGE-A3 with AS15 immunostimulant (MAGE-A3 immunotherapeutic; 300 μg MAGE-A3 antigen plus 420 μg CpG 7909 reconstituted in AS01B to a total volume of 0·5 mL), or placebo, over a 27-month period: five doses at 3-weekly intervals, followed by eight doses at 12-weekly intervals. The co-primary outcomes were disease-free survival in the overall population and in patients with a potentially predictive gene signature (GS-positive) identified previously and validated here via an adaptive signature design. The final analyses included all patients who had received at least one dose of study treatment; analyses for efficacy were in the as-randomised population and for safety were in the as-treated population. This trial is registered with ClinicalTrials.gov, number NCT00796445.FINDINGSBetween Dec 1, 2008, and Sept 19, 2011, 3914 patients were screened, 1391 randomly assigned, and 1345 started treatment (n=895 for MAGE-A3 and n=450 for placebo). At final analysis (data cutoff May 23, 2013), median follow-up was 28·0 months [IQR 23·3-35·5] in the MAGE-A3 group and 28·1 months [23·7-36·9] in the placebo group. Median disease-free survival was 11·0 months (95% CI 10·0-11·9) in the MAGE-A3 group and 11·2 months (8·6-14·1) in the placebo group (hazard ratio [HR] 1·01, 0·88-1·17, p=0·86). In the GS-positive population, median disease-free survival was 9·9 months (95% CI 5·7-17·6) in the MAGE-A3 group and 11·6 months (5·6-22·3) in the placebo group (HR 1·11, 0·83-1·49, p=0·48). Within the first 31 days of treatment, adverse events of grade 3 or worse were reported by 126 (14%) of 894 patients in the MAGE-A3 group and 56 (12%) of 450 patients in the placebo group, treatment-related adverse events of grade 3 or worse by 36 (4%) patients given MAGE-A3 vs six (1%) patients given placebo, and at least one serious adverse event by 14% of patients in both groups (129 patients given MAGE-A3 and 64 patients given placebo). The most common adverse events of grade 3 or worse were neoplasms (33 [4%] patients in the MAGE-A3 group vs 17 [4%] patients in the placebo group), general disorders and administration site conditions (25 [3%] for MAGE-A3 vs four [<1%] for placebo) and infections and infestations (17 [2%] for MAGE-A3 vs seven [2%] for placebo). No deaths were related to treatment.INTERPRETATIONAn antigen-specific immunotherapeutic alone was not efficacious in this clinical setting. Based on these findings, development of the MAGE-A3 immunotherapeutic for use in melanoma has been stopped.FUNDINGGlaxoSmithKline Biologicals SA.

100 项与 Recombinant MAGE-A3 protein immunotherapy(GlaxoSmithKline Plc) 相关的药物交易

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适应症	最高研发状态	国家/地区	公司	日期
膀胱癌	临床2期	-	GSK Plc	-

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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


NCT00706238 (CTgov)	临床2期	转移性黑色素瘤 \| MAGE-A3阳性肌层浸润性膀胱癌	5	GSK Biologicals' Recombinant MAGE-A3 Antigen-Specific Cancer Immunotherapeutic (ASCI) GSK1203486A	憲網鑰獵積遞淵繭獵選(構獵窪範範壓構製窪糧) = 範構壓夢網餘選鏇願繭襯製餘製遞範夢顧觸壓 (淵遞憲製鏇築壓顧遞廠, 鏇壓築築願鏇鹽鑰齋餘 ~ 觸遞鑰構鹹憲顧憲繭觸) 更多	-	2019-06-03
ASCO2008 人工标引	临床2期	转移性黑色素瘤	75	MAGE-A3 protein + AS15	(鹽範窪選獵獵鹽構膚鑰) = 觸憲鏇蓋衊淵鹽蓋淵壓願窪憲衊夢壓糧齋蓋糧 (網鏇鑰繭獵鹽繭淵簾鏇 ) 更多	积极	2008-05-20
ASCO2008 人工标引	临床2期	转移性黑色素瘤	75	MAGE-A3 protein + AS02B	(鹽範窪選獵獵鹽構膚鑰) = 鹹繭夢淵範簾鹹廠製廠願窪憲衊夢壓糧齋蓋糧 (網鏇鑰繭獵鹽繭淵簾鏇 ) 更多	积极	2008-05-20
ASCO2008	临床2期	非小细胞肺癌辅助	182	MAGE-A3 recombinant protein + Adjuvant System	(繭繭醖鬱簾鑰鬱繭淵顧) = 齋製簾獵鑰鹽廠夢觸衊鬱網蓋製願製簾醖顧範 (構願範網繭艱淵蓋憲獵 )	-	2008-05-20