A Randomized Phase II Clinical Trial on Intratumoral AS01B/ipilimumab Plus Intravenous Nivolumab with or Without Autologous CD1c(BDCA-1)+ / CD141(BDCA-3)+ Myeloid Dendritic Cells.

This phase II trial aims at investigating the role and effect of autologous CD1c (BDCA-1)+ myeloid dendritic cells in combination with intratumoral injection of the CTLA-4 blocking monoclonal antibody (mAb) ipilimumab and the immunoligand AS01B compared to a combinatorial immunotherapy regimen using intratumoral injection of the CTLA-4 blocking monoclonal antibody (mAb) ipilimumab and the immunoligand AS01B. Concomitantly, nivolumab (a PD-1 blocking mAb) will be administered intravenously in both arms.

开始日期2018-01-29

申办/合作机构

Universitair Ziekenhuis Brussel

100 项与 Autologous CD1c (BDCA-1)+ myDC(Universitair Ziekenhuis Brussel) 相关的临床结果

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100 项与 Autologous CD1c (BDCA-1)+ myDC(Universitair Ziekenhuis Brussel) 相关的转化医学

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100 项与 Autologous CD1c (BDCA-1)+ myDC(Universitair Ziekenhuis Brussel) 相关的专利（医药）

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项与 Autologous CD1c (BDCA-1)+ myDC(Universitair Ziekenhuis Brussel) 相关的文献（医药）

2024-01-01·Journal for ImmunoTherapy of Cancer

Intratumoral administration of the immunologic adjuvant AS01_Bin combination with autologous CD1c (BDCA-1)⁺/CD141 (BDCA-3)⁺myeloid dendritic cells plus ipilimumab and intravenous nivolumab in patients with refractory advanced melanoma

Article

作者: Tuyaerts, Sandra ; Raeymaeckers, Steven ; Geeraerts, Xenia ; Neyns, Bart ; Dirven, Iris ; Stevens, Latoya ; Forsyth, Ramses ; Van Riet, Ivan ; Boisson, Anais ; Tijtgat, Jens ; Willard-Gallo, Karen ; Schwarze, Julia Katharina ; Vounckx, Manon

BackgroundPatients with advanced melanoma who progress after treatment with immune checkpoint-inhibitors (ICI) and BRAF-/MEK-inhibitors (ifBRAFV600mutated) have no remaining effective treatment options. The presence of CD1c (BDCA-1)+and CD141 (BDCA-3)+myeloid dendritic cells (myDC) in the tumor microenvironment correlates with pre-existing immune recognition and responsiveness to immune checkpoint blockade. The synthetic saponin-based immune adjuvant AS01Benhances adaptive immunity through the involvement of myDC.MethodsIn this first-in-human phase I clinical trial, patients with metastatic melanoma refractory to ICI and BRAF-/MEK inhibitors (when indicated) were recruited. Patients received an intravenous administration of low-dose nivolumab (10 mg, every 2 weeks) plus an intratumoral (IT) administration of 10 mg ipilimumab and 50 µg (0.5 mL) AS01B(every 2 weeks). All myDC, isolated from blood, were injected on day 2 into the same metastatic lesion. Tumor biopsies and blood samples were collected at baseline and repeatedly on treatment. Multiplex immunohistochemistry (mIHC) was performed on biopsy sections to characterize and quantify the IT and peritumoral immune cell composition.ResultsStudy treatment was feasible and well tolerated without the occurrence of unexpected adverse events in all eight patients. Four patients (50%) obtained a complete response (CR) in the injected lesions. Of these, two patients obtained an overall CR, and one patient a partial response. All responses are ongoing after more than 1 year of follow-up. One additional patient had a stable disease as best response. The disease control rate was 50%. Median progression-free survival and overall survival were 24.1 and 41.9 weeks, respectively. Baseline tumor biopsies from patients who responded to treatment had features of T-cell exclusion. During treatment, there was an increased T-cell infiltration, with a reduced mean distance between T cells and tumor cells. Peripheral blood immune cell composition did not significantly change during study treatment.ConclusionsCombining an intratumoral injection of CD1c (BDCA-1)+and CD141 (BDCA-3)+myDC with repeated IT administration of ipilimumab and AS01Band systemic low-dose nivolumab is safe, feasible with promising early results, worthy of further clinical investigation.Trial registration numberClinicalTrials.gov identifierNCT03707808.

100 项与 Autologous CD1c (BDCA-1)+ myDC(Universitair Ziekenhuis Brussel) 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
晚期恶性实体瘤	临床2期	比利时	Universitair Ziekenhuis Brussel	2018-01-29

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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


NCT03707808 (ESMO2024) 人工标引	临床1期	难治性黑色素瘤	6	Autologous CD1c(BDCA-1)+/CD141(BDCA-3)+myeloid dendritic cells (myDC) with AS01B plus ipilimumab (IPI) and nivolumab (NIVO)	(夢餘製鬱網艱繭簾鑰獵) = Treatment related adverse events (TRAE) included transient grade 1/2 injection site reactions and constitutional symptoms. One pt experienced a grade 3 systemic inflammatory syndrome with a lymphocytic peritoneal exudate (responsive to corticosteroids). There were no grade 4-5 TRAE. 憲壓襯淵簾網簾齋鹽窪 (淵範襯鑰觸獵顧願廠積 )	积极	2024-09-14
NCT03707808 (Pubmed) 人工标引	临床1期	难治性黑色素瘤 CD1c (BDCA-1) \| CD141 (BDCA-3)	8	autologous CD1c (BDCA-1)+ myDCASipilimumablognivolumab(BDCA-1)+/CD141 (BDCA-3)+ myeloid dendritic cells + ipilimumab + intravenous nivolumab	(夢顧窪艱構積夢鹽網糧) = 簾蓋襯構繭遞齋積鬱鑰選選鹽鏇鹽觸餘膚選遞 (選鹹糧廠構願夢選醖憲 ) 更多	积极	2024-01-11
NCT03707808 (SITC 12022 \| SITC 22022) 人工标引	临床1期	BRAF V600 突变阳性黑色素瘤 BRAF V600	8	CD1c (BDCA-1)+/CD141 (BDCA-3)+ myDC(Universitair Ziekenhuis Brussel)+nivolumab+ipilimumab	(願遞網鹽餘醖築觸願醖) = 網餘繭範鹽選膚壓夢憲簾繭壓鑰醖鏇襯壓艱鹽 (選構積鏇膚觸壓窪襯餘, 5.193 ~ 15.007) 更多	积极	2022-11-01
NCT03707808 (ASCO 12019 \| ASCO 22019) 人工标引	临床1期	HR阳性/HER2低表达实体瘤二线	6	ipilimumab+Avelumab+Nivolumab+Autologous CD1c (BDCA-1)+ Myeloid Dendritic Cells	(廠顧壓製遞艱遞淵繭鹹) = transient G 2 local pain at injection site in 2 pts, G1 pruritus in 2 pts, G2 pneumonitis in 1 pt, G1 rash in 1 pt, pruritus and redness of the skin overlaying the injected lesion in 1 pt 糧繭窪齋憲艱築鏇鏇窪 (積餘網蓋憲窪齋觸鑰獵 ) 更多	积极	2019-05-31