Phase I/II Trial of Ipilimumab or Nivolumab With BMS-986156 and Hypofractionated Stereotactic Radiation Therapy in Patients With Advanced Solid Malignancies

This phase I/II trial studies the side effects and best dose of anti-glucocorticoid-induced tumor necrosis factor receptor (GITR) agonistic monoclonal antibody BMS-986156 (BMS-986156) when given together with ipilimumab and nivolumab with or without stereotactic body radiation therapy and to see how well they work in treating patients with lung/chest or liver cancer that has spread to other places in the body. Immunotherapy with monoclonal antibodies, such as BMS-986156, ipilimumab, and nivolumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Stereotactic body radiation therapy uses special equipment to position a patient and deliver radiation to tumors with high precision. This method can kill tumor cells with fewer doses over a shorter period and cause less damage to normal tissue. It is not yet known whether giving BMS-986156, ipilimumab, and nivolumab with or without stereotactic body radiation therapy will work better in treating patients with lung/chest or liver cancers.

开始日期2019-08-19

申办/合作机构

The University of Texas MD Anderson Cancer Center

NCT02598960

/ Completed临床1/2期

A Phase 1/2a Dose Escalation and Cohort Expansion Study for Safety, Tolerability, and Efficacy of BMS-986156 Administered Alone and in Combination With Nivolumab (BMS-936558, Anti PD-1 Monoclonal Antibody) in Advanced Solid Tumors

The purpose of this study is to evaluate the safety and tumor-shrinking ability of experimental medication BMS-986156, when given by itself or in combination with nivolumab in patients with solid cancers that are advanced or cancers that have spread.

开始日期2015-10-14

申办/合作机构

Bristol Myers Squibb Co.

100 项与 BMS-986156 相关的临床结果

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100 项与 BMS-986156 相关的转化医学

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100 项与 BMS-986156 相关的专利（医药）

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项与 BMS-986156 相关的文献（医药）

2025-05-01·Journal for ImmunoTherapy of Cancer

Rationale and feasibility of a rapid integral biomarker program that informs immune-oncology clinical trials: the ADVISE trial

Article

作者: Tam, Rachel ; Luke, Jason J ; Gupta, Akshita ; Lee, George ; Reilly, Tim ; Szabo, Peter ; Yao, David ; Dutta, Santanu ; Taube, Janis ; Bao, Riyue ; Massey, Ashish ; Bever, Katherine ; Neely, Jaclyn ; Hodi, F Stephen

Background:

ADVISE (ADaptiVe biomarker trial that InformS Evolution of therapy) (NCT03335540) was a biomarker-adapted feasibility clinical trial of immunohistochemistry (IHC) to inform combination immuno-oncology (I-O) treatment.

Methods:

To inform I-O combination selection, messenger RNA expression analyses from The Cancer Genome Atlas evaluated associations between programmed death 1/programmed death ligand 1 (PD-1/PD-L1) and other I-O-associated genes. Tumor tissue blocks of melanoma, non-small cell lung cancer, renal cell carcinoma, urothelial carcinoma, squamous cell carcinoma of the head and neck, and gastroesophageal junction/gastric cancer were stained by IHC to assess expression of CD8, colony-stimulating factor 1 receptor, glucocorticoid-induced tumor necrosis factor receptor (GITR), indoleamine 2,3-dioxygenase 1, lymphocyte-activation gene 3, NKp46, forkhead box P3, and PD-L1. These results facilitated an I-O treatment selection algorithm where patient biopsy results dictated allocation into combinations of nivolumab with cabiralizumab, urelumab, linrodostat mesylate, relatlimab, BMS-986156 (anti-GITR), lirilumab, ipilimumab, or irradiation. The primary endpoint was the proportion of patients with qualified baseline tumor biopsy specimens where decision-enabling biomarker analysis was completed within 12 business days to select an I-O combination therapy.

Results:

Correlation of PD-1/L1 and I-O-associated genes varied across the spectrum of T-cell-inflamed versus non-inflamed tumors; however, tumors with low/intermediate PD-L1 expression demonstrated distinct upregulation of immune markers grouped by cell type (T cell, macrophage, etc). IHC analyses of I-O naïve tumors corroborated these findings with distinct immune target upregulation in low-to-intermediate inflamed tumors and significant associations between IHC-detected markers and T-cell inflammation score across most markers. In the clinical trial, 20/23 (87%) of eligible patients were successfully allocated and started on treatment within the 12-day window, meeting the primary endpoint. The safety profile appeared to generally align with those reported for the individual combinations from other trials. No treatment responses occurred. Most patients were allocated to the cabiralizumab treatment arm.

Conclusions:

Actualization of a patient-specific I-O combination treatment selection strategy is feasible, however, determination of de novo integral biomarker thresholds of novel I-O targets to facilitate effective treatment of PD-1-refractory cancer remains fraught. These data emphasize the difficulty of integral biomarker development for I-O in translating from immunotherapy treatment-naïve biospecimens to the selection of patients in the PD-1-refractory state.

Trial registration number:

NCT03335540.

2024-10-01·Journal for ImmunoTherapy of Cancer

Phase I/II study of BMS-986156 with ipilimumab or nivolumab with or without stereotactic ablative radiotherapy in patients with advanced solid malignancies

Article

作者: Chang, Joe Y ; Li, Wei ; Hong, David S ; Verma, Vivek ; Xu, Xinyan ; Dumbrava, Ecaterina E ; Karp, Daniel D ; Shroff, Girish S ; Chen, Aileen ; Rodon Ahnert, Jordi ; Comeaux, Nathan I ; Welsh, James

Background:

BMS-986156 is an agonist of the glucocorticoid-induced tumor necrosis factor receptor (TNFR)-related protein (GITR) and promotes increased effector T-cell activation. Combined anti-GITR, anti-programmed death-1, anti-cytotoxic T-lymphocyte-associated protein 4 antibodies and radiotherapy improve tumor control in preclinical studies. Herein we describe the results of the safety and efficacy of BMS-986156+ipilimumab or nivolumab with/without stereotactic ablative radiotherapy (SABR) in patients with advanced solid cancers (NCT04021043).

Methods:

This open-label, multigroup, single-center phase I/II study enrolled patients with histologically-confirmed stage IV solid cancers resistant to standard treatments. Group 1 (G1, n=20) received four cycles of ipilimumab (3 mg/kg) plus BMS-986156 (30 mg as dose level 1 (L1) or 100 mg as dose level 2 (L2)), every 3 weeks (Q3W). Group 2 (G2, n=10) received four cycles of ipilimumab (3 mg/kg) plus BMS-986156 (dose as determined in G1, Q3W) with SABR (50 Gy/4 fx or 60–70 Gy/10 fx to liver/lung lesions. Group 3 (G3, n=20) received four cycles of nivolumab (480 mg) plus BMS-986156 (30 mg), every 4 weeks with SABR. Maintenance nivolumab could be given up to 2 years. Tumor responses were assessed every 1–3 months until progression, using immune-related response criteria.

Results:

50 patients were enrolled between 10/2019 and 12/2021. Patients received a median of 3 (IQR 2–4.25) initial treatment cycles. 100 mg BMS-986156 with ipilimumab was tolerated well. Five discontinued BMS-986156 with ipilimumab due to treatment-related adverse events (TRAEs), with three in G1/L1, one in G1/L2 and one in G2, respectively. 22 patients (44%) experienced Grade 1–3 TRAEs (6, 4, 5, 7 patients for G1/L1, G1/L2, G2, G3). Six (12%) had Grade 3 TRAEs (2, 2, 1, 1 for G1/L1, G1/L2, G2, G3), with elevated alanine aminotransferase (n=3, in G1/L2, G2 and G3) and aspartate aminotransferase (n=2, in G2 and G3) being the most common. There was no Grade 4–5 TRAEs. Overall, 19/39 (48.7%) patients eligible for efficacy analysis had stable disease and 3 (7.7%) achieved a partial response. Out-of-field (abscopal) disease control rate (ACR) and out-of-field (abscopal) response rate (ARR) were 38.5% and 7.7%, respectively, with the highest ACR (50%, 9/18) and ARR (11.1%, 2/18) in G3.

Conclusions:

BMS-986156 was well-tolerated with ipilimumab, nivolumab, with or without SABR. Outcomes were encouraging in this population, as more than half of patients had stable disease/partial response.

2023-04-01·ESMO open

Pharmacodynamic activity of BMS-986156, a glucocorticoid-induced TNF receptor-related protein agonist, alone or in combination with nivolumab in patients with advanced solid tumors

Article

作者: Hedvat, C ; Wang, R ; Sun, Y ; Walsh, A M ; Basavanhally, T ; Li, Z ; Shao, X ; Locke, D ; Greenawalt, D M ; Novosiadly, R ; Baxi, V ; Patah, P

BACKGROUND:

The success of immune checkpoint inhibitors has revolutionized cancer treatment options and triggered development of new complementary immunotherapeutic strategies, including T-cell co-stimulatory molecules, such as glucocorticoid-induced tumor necrosis factor receptor-related protein (GITR). BMS-986156 is a fully agonistic human immunoglobulin G subclass 1 monoclonal antibody targeting GITR. We recently presented the clinical data for BMS-986156 with or without nivolumab, which demonstrated no compelling evidence of clinical activity in patients with advanced solid tumors. Here, we further report the pharmacodynamic (PD) biomarker data from this open-label, first-in-human, phase I/IIa study of BMS-986156 ± nivolumab in patients with advanced solid tumors (NCT02598960).

MATERIALS AND METHODS:

We analyzed PD changes of circulating immune cell subsets and cytokines in peripheral blood or serum samples collected from a dataset of 292 patients with solid tumors before and during treatment with BMS-986156 ± nivolumab. PD changes in the tumor immune microenvironment were measured by immunohistochemistry and a targeted gene expression panel.

RESULTS:

BMS-986156 + nivolumab induced a significant increase in peripheral T-cell and natural killer (NK) cell proliferation and activation, accompanied by production of proinflammatory cytokines. However, no significant changes in expression of CD8A, programmed death-ligand 1, tumor necrosis factor receptor superfamily members, or key genes linked with functional parameters of T and NK cells were observed in tumor tissue upon treatment with BMS-986156.

CONCLUSIONS:

Despite the robust evidence of peripheral PD activity of BMS-986156, with or without nivolumab, limited evidence of T- or NK cell activation in the tumor microenvironment was observed. The data therefore explain, at least in part, the lack of clinical activity of BMS-986156 with or without nivolumab in unselected populations of cancer patients.

项与 BMS-986156 相关的新闻（医药）

2024-07-07

·生物制品圈

罗氏：失败，接二连三

TIGIT靶点成药之路仍未看到尽头，与之相比，负面消息倒是时有看到。 7月3日，罗氏旗下公司基因泰克披露，tiragolumab在转移性非鳞状非小细胞肺癌II/III期研究（SKYSCRAPER-06）折戟。由于无法跟对照组拉开疗效差距，该项临床不得不叫停。罗氏股价消息公布在次日开盘跌出3%，但随后又逐渐收复失地——或许在更长的时间维度，投资者已经被类似的失败脱敏，见怪不怪了。 2009年，TIGIT在Nature Immunology上首次见诸公众；而再往前追溯，可定位于2002年基因泰克科学家在实验室的一次发现。该靶点的热度转向，发生在2020年5月，源自罗氏公布的一则试验结果。正是这次失败的Tiragolumab，在当时联合PD-L1单抗Tecentriq，显示出不俗的初步数据。各家公司入局，故事却并没有朝着众人预期的方向发展。包括Tiragolumab在内，失败的TIGIT抑制剂项目并不少见。客观来说，小细胞肺癌本就是“研发黑洞”，TIGIT靶点的前景，主要取决于能否在非小细胞癌领域取得成功。不过，Tiragolumab作为TIGIT药物的先驱，它的失利依然会让市场有所思考。至少，它可能会改变市场对TIGIT未来的理解和预期。罗氏该如何走出下一步？TIGIT靶点最终能迈向成功吗？ 1 罗氏心不死说到罗氏在TIGIT和非小细胞肺癌上吃的亏，这不是第一次。罗氏是第一家将TIGIT靶点开发为抗体药物的MNC。临床前数据让该公司为之信心满满，一度连开了13项临床实验，开头两局就剑指最大的癌肿，小细胞肺癌和非小细胞肺癌。可惜，2022年TIGIT靶点先后遭遇两次打击。先是2022年3月，罗氏宣布PD-L1+TIGIT+化疗联合治疗小细胞肺癌的III期临床未达到PFS和OS共同主要终点。紧接着，2022年5月，罗氏再次宣布，PD-L1+TIGIT联合治疗PD-L1高表达非小细胞肺癌的III期临床失败，未能达到PFS主要终点。领头药企在两项关键临床试验的失败，无疑给TIGIT的未来增添了巨大的不确定性。不过，大部分大药厂依然对其充满期待。即便在两度遭受打击后，罗氏仍然未放弃对TIGIT的押注。罗氏曾表示，它将继续TIGIT的研究，直到总生存期结果出炉，同时其针对一线食管鳞癌适应症的III期（SKYSCRAPER-08）临床研究将公布中国人群结果。此外，在对2023年的展望中，罗氏也把TIGIT资产列在值得关注的计划内。时间来到今天，不“死心”的罗氏公布了SKYSCRAPER-06研究数据，该研究随机将患者分为两组，一组接受tiragolumab和Tecentriq治疗，另一组接受默沙东的Keytruda和化疗治疗。参与者患有之前未接受过治疗的局部晚期不可切除或转移性非鳞状非小细胞肺癌。罗氏发现，在第一次中期分析中，Keytruda的生存数据表现更佳，PFS评估产生的风险比为1.27。同时，风险比高于1，这代表对照组的表现优于研究治疗组，患者使用Keytruda比使用tiragolumab更长寿。罗氏仍旧无法打败“K药”。 2 家家有本难念的经在TIGIT赛道上负重前行的，不止罗氏自己。 2021年12月底，百济神州将TIGIT抑制剂ociperlimab的海外权益转给诺华，交易金额29亿美元，让TIGIT轰动一时。如今长尾效应仍在持续。 2022年12月19日，吉利德/Arcus发布的TIGIT/PD-L1联合疗法的II期临床（ARC-7）结果。从结果来看，ARC-7数据积极。与PD-1抑制剂zimberelimab作为单一疗法相比，三个治疗组zimberelimab单药、zimberelimab/domvanalimab（TIGIT）双药、zimberelimab/domvanalimab/etrumadenant三药，均达到PFS。默沙东针对TIGIT单抗的研发同样在继续中。目前默沙东TIGIT单抗+K药+化疗的临床试验已进入临床III期。MCN眼中的TIGIT靶点还能再“抢救”一下。目前，全球针对TIGIT靶点已研发出多款药物，至少5款进入III期临床，近10款进入2期临床，近20款进入1期临床。在研TIGIT靶向药药物类型多样，涉及单抗、双抗、化药、融合蛋白，其中TIGIT靶向双抗作用靶点多样，涉及PD-1/TIGIT、PD-L1/TIGIT、CD112R/TIGIT、LAG3/TIGIT、TGF-β/TIGIT等。 Tiragolumab、MK-7684A（Pembrolizumab/Vibostolimab)、Ociperlimab、Domvanalimab和Vibostolimab等药物进展较快，目前已进入III期临床。图丨全球在研TIGIT管线一览，来源：公司官网据不完全统计，近年来全球药企围绕TIGIT靶向药达成了数项交易。 2018年4月，阿斯利康与Compugen签订独家授权协议。据协议，Compugen将包括COM902在内的TIGIT单抗独家许可给阿斯利康以开发双抗和多抗。 2018年12月，Astellas以4亿美元的价格收购Potenza Therapeutics，获得后者TIGIT、NRP1、GITR三个抗体。 2019年4月，Mereo BioPharma收购Oncomed Phaemaceuticals，获得后者包括TIGIT抗体Etigilimab（现名为MPH-313）在内的4个项目。 2020年5月，吉利德与Arcus Biosciences达成一项为期10年的合作，共同开发和商业化Arcus Biosciences研发管线中的候选药物，其中包括PD-1抑制剂和TIGIT抑制剂。2021年11月，吉利德宣布行使选择权，获得Arcus Biosciences包括TIGIT单抗domvanalimab和AB308在内的多个研发项目。 2021年5月，BMS宣布与Agenus达成一项15.6亿美元的授权协议，获得Agenus专有的双特异性抗体项目AGEN1777的全球独家授权。 2021年6月，GSK与iTeos Therapeutics达成合作，共同开发和商业化EOS-448。 2021年12月，百济神州与诺华达成合作协议，授予诺华在美国、加拿大、欧洲多国及日本开发、生产和商业化TIGIT抗体Ociperlimab的权益。而诺华将支付3亿美元预付款，6亿美元或7亿美元的额外付款，18.95亿美元里程碑，以及20%-25%的销售分成。然而，诺华与百济神州终止了该合作。相比于交易的火热，TIGIT的对外表现有点“雷声大，雨点小”的意味，留给外界的叹息声似乎更多。在罗氏失败后，GSK与合作伙伴iTeos重新评估了TIGIT项目，最终还是决定继续TIGIT项目。 BMS在潜在的风险面前，同样选择了撤退。 2023年2月，BMS在公布财报时透露，决定终止TIGIT抑制剂BMS-986207的II期临床试验，该药是与CTLA-4抑制剂Yervoy、PD-1抑制剂Opdivo构成三联疗法的一部分。 BMS首席医学官Samit Hirawat透露，他们在联合用药时观察到了毒性，出于安全考虑，BMS决定终止这项试验。另一家大药企诺华，虽然没有放弃TIGIT单抗的研发，但其研发TIGIT的进度却放慢了。关于TIGIT，大家都在谨慎中带着一丝拘谨，但总体来说，“唱衰”的声音更多，罗氏的失败可能仍会接连上演。识别微信二维码，添加生物制品圈小编，符合条件者即可加入生物制品微信群！请注明：姓名+研究方向！版权声明本公众号所有转载文章系出于传递更多信息之目的，且明确注明来源和作者，不希望被转载的媒体或个人可与我们联系(cbplib@163.com)，我们将立即进行删除处理。所有文章仅代表作者观点，不代表本站立场。

临床3期临床失败临床2期临床结果临床终止

2024-03-17

·生物制药小编

靶向肿瘤Treg的五类疗法

【前言】瘤内浸润的Treg细胞亚群复杂，通过不同途径促进免疫抑制微环境的塑造，是肿瘤。也因此，很多已上市的抗体疗法都和Treg作用相关，也有希望特异性影响Treg的疗法在开发中。Front. Immunol.（一）通过表面蛋白特异性耗竭Treg进入临床阶段的疗法包括：靶点药物/管线名称其他CD25daclizumab人源IgG1单抗basiliximabADCT-301ADCRO7296682IL-2非阻断抗体RM-1995近红外光免疫疗法Denileukin diftitox重组免疫毒素CTLA-4Ipilimumab人源化IgG1单抗ADU-1604NurulimabTicilimumab人源化IgG2单抗XMAB20717CTLA-4/PD-1双特异性单抗XMAB22841CTLA-4/LAG-3双特异性单抗ATOR-1015CTLA-4/OX40双特异性单抗OX40MEDI6383人OX40L-IgG4 Fc融合蛋白PF-04518600激动型单抗BMS 986178BGB-A445MEDI6469MOXR0916MEDI0562GITRMEDI1873激动型六价GITR配体融合蛋白TRX518人源化、非耗竭性、琼脂糖基IgG1单抗MK-1248人源化IgG4单抗BMS-986156人源IgG1单抗GWN323ICOSJTX-2011激动型人源化IgG1单抗KY1044MEDI-570Fc段糖基化人源化单抗GSK3359609XMAB23104ICOS/PD-1双特异性单抗肿瘤浸润Treg抑制相关的表面分子表达包括：CD25、CTLA-4、PD-1、ICOS、LAG-3和TIGIT；TNF受体超家族GITR、4-1BB和OX-40；趋化因子受体CCR4、CCR5和CCR10。Treg细胞还可以通过释放IL-10、TGF-β和IL-35等抗炎细胞因子来抑制TME的免疫反应。几种CTLA-4单克隆抗体还可以通过ADCC效应杀伤Ti-Tregs。然而，一些临床研究表明，在CTLA-4抗体给药后，肿瘤内的Tregs数量不会减少，反而促进了Ti-Tregs的CD28依赖性扩增。此外，由于微环境中的其他免疫细胞也表达CTLA-4，因此非选择性靶向CTLA-4可能会无意中减少抗肿瘤免疫细胞。许多研究已经探索了以CD25为靶点的抗肿瘤策略，或者将IL-2与细胞毒分子或CD25 ADC结合以耗尽Treg细胞。然而，这些方法在不同的背景下表现出不同的有效性。（二）减少Tregs募集：抑制趋化因子信号通路进入临床阶段的疗法包括：靶点药物/管线名称特征CCR4MogamulizumabFc段糖基化人源化单抗FLX475口服特异性激动剂CCR8GS-1811Fc段糖基化人源化单抗BAY3375968BMS-986340S-531011通过抑制趋化因子信号通路，Tregs在肿瘤中的积聚可以得到缓解(肿瘤浸润Treg的趋化和代谢特征)。很早就有在小鼠实验中实验CCR10或CCR5单抗，显示能显著延缓肿瘤生长。CCR4单抗还能通过ADCC效应特异性地清除Treg。（三）减弱Tregs相关细胞间信号进入临床阶段的疗法包括：靶点药物/管线名称特征PI3K8Parsaclisib小分子抑制剂IOA-244AZD8186LCKDasatinib多靶点TKIImatinibTreg细胞通过高表达CD39和CD73来适应微环境，最终将瘤内的ATP转化为腺苷。CD39：当ATP作用于Treg的P2XR时，可以诱导Treg的凋亡并抑制Treg的功能(172,173)。CD39可降低TME中的ATP水平，间接保护Treg细胞免受ATP诱导的细胞凋亡。CD73：提高了微环境中的腺苷浓度。腺苷与效应T细胞膜上的A2aR和A2bR结合，从而抑制其活性。IDO：作为一种色氨酸消耗酶，可导致TME内色氨酸水平降低，从而影响T细胞的激活及其抗肿瘤能力。值得注意的是，给予免疫检查点抑制剂后，TME中过表达IDO，同样导致Tonvs功能障碍，Tregs和MDSCs激活和增殖水平提高，建立了免疫抑制环境。不过，尽管Epacadostat在内的几种口服IDO1抑制剂在过去几年中已进入人体临床试验，没有出现重大安全问题，但其单药试验并未达到客观疗效。（四）靶向Treg代谢进入临床阶段的疗法包括：靶点药物/管线名称特征CD36VT1021多为抑制剂MCT1AZD3965IDOEpacadostatNLG802GDC-0919CD73LY3475070小分子酶抑制剂CPI-006MEDI9447Sym024CD39TTX-030SRF617肿瘤细胞与TI-Tregs有一些共同的代谢特征。在人源卵巢癌、结肠癌和黑色素瘤的小鼠模型中，ROS可诱导Tregs的凋亡。此外，特定浓度的乳酸为TI-Tregs提供碳源以产生磷酸烯醇式丙酮酸(糖酵解的中间体)。然而，目前尚不清楚在TME中限制Treg代谢最终对免疫有利还是有害。正面作用的靶点包括CD36，例如在黑色素瘤移植小鼠模型中，CD36拮抗剂破坏脂质代谢，从而选择性地耗尽Ti-Tregs，恢复抗体对PD-1的效力，而不会产生严重的自身免疫反应。PI3K-AKT-mTOR通路作为协调糖酵解的枢纽，也是Treg代谢靶点之一。黑色素瘤小鼠模型中，雷帕霉素和GO-Y030(mTOR抑制剂)可通过限制葡萄糖摄取和糖酵解，来限制Tregs的数量和功能。此外，当Poly-G3和ssRNA40在体外与人卵巢癌细胞共同培养时，可以刺激TLR8信号，干扰mTOR-HIF-1α诱导的葡萄糖代谢，降低Treg的功能。在胃癌临床前模型中，PI3K-β抑制剂GSK2636771减少了Tregs中游离FA的产生、脂肪的吸收和代谢，抑制了它们的迁移和功能。此类药物还通过信号传递、表观遗传调节和翻译后修饰对Treg产生影响。例如，idelalisib(第一种用于人类慢性淋巴细胞白血病的PI3K-δ抑制剂)可选择性地阻止T细胞分化为Treg细胞和后续分泌IL-10的能力。脂质代谢：主要依赖脂肪酸合成(FAS)和FAO来扰乱肿瘤浸润Treg细胞的代谢适应性。在小鼠黑色素瘤模型中，CD36等脂质代谢靶点比CTLA-4和OX40等传统靶点显示出更好的特异性，阻止了功能性Tregs的积累，而不会系统性地耗竭全身Tregs。抗CD36和抗PD-1阻断的联合治疗可防止小鼠在治疗后出现严重的自身免疫。氨基酸代谢：通过吲哚胺2，3-双加氧酶(IDO)靶向犬尿氨酸途径有可能消除小鼠胶质母细胞瘤模型中的Tregs。不过几种IDO1抑制剂目前尚无较好数据，也少有进入临床阶段的管线。（五）靶向TME进入临床阶段的疗法包括：靶点药物/管线名称特征VEGFBevacizumabRamucirumabVEGFR2单抗Sorafenib多靶点小分子抑制剂TGF-βGalunisertibTGFR1抑制剂M7824PD-1/TGFβTrapTreg在肿瘤微环境中对血管新生具有极大的促进作用。小结：Treg细胞的特征分子和代谢途径并不是它们自己独有，而是与效应T细胞和外周Tregs共享靶点。因此，全身给药方法可能导致消除或抑制肿瘤外的非肿瘤Tregs以及其他效应细胞，不仅抑制pTreg功能，破坏免疫动态平衡，引发自身免疫性炎症，而且还减弱抗肿瘤效率。也就是说，要么找到表达水平具有足够特异性的单一靶点，要么采用复合靶点以改善这种表达差异。参考文献：1.Qin D, Zhang Y, Shu P, Lei Y, Li X and Wang Y (2024) Targeting tumor-infiltrating tregs for improved antitumor responses. Front. Immunol. 15:1325946. doi: 10.3389/fimmu.2024.13259462.Wang Y, Huang T, Gu J, Lu L. Targeting the metabolism of tumor-infiltrating regulatory T cells. Trends Immunol. 2023 Aug;44(8):598-612. doi: 10.1016/j.it.2023.06.001. 3.Christopher Tay, Atsushi Tanaka, Shimon Sakaguchi,Tumor-infiltrating regulatory T cells as targets of cancer immunotherapy,Cancer Cell,Volume 41, Issue 3,2023.doi:10.1016/j.ccell.2023.02.014.

免疫疗法抗体药物偶联物临床申请

100 项与 BMS-986156 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
晚期恶性实体瘤	临床2期	美国	Bristol Myers Squibb Co.	2015-10-14
晚期恶性实体瘤	临床2期	澳大利亚	Bristol Myers Squibb Co.	2015-10-14
晚期恶性实体瘤	临床2期	比利时	Bristol Myers Squibb Co.	2015-10-14
晚期恶性实体瘤	临床2期	加拿大	Bristol Myers Squibb Co.	2015-10-14
晚期恶性实体瘤	临床2期	法国	Bristol Myers Squibb Co.	2015-10-14
晚期恶性实体瘤	临床2期	德国	Bristol Myers Squibb Co.	2015-10-14
晚期恶性实体瘤	临床2期	意大利	Bristol Myers Squibb Co.	2015-10-14
晚期恶性实体瘤	临床2期	荷兰	Bristol Myers Squibb Co.	2015-10-14
晚期恶性实体瘤	临床2期	西班牙	Bristol Myers Squibb Co.	2015-10-14
晚期恶性实体瘤	临床2期	瑞士	Bristol Myers Squibb Co.	2015-10-14

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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


NCT04021043 (Phase I/II study of BMS-986156, Pubmed \| J Immunother Cancer) 人工标引	临床1/2期	晚期恶性实体瘤	50	BMS-986156+ipilimumab	鹽醖製襯糧鏇簾憲鹹憲(齋網艱觸觸衊願鑰範廠) = 鑰鏇選繭艱膚夢醖衊廠廠願夢簾膚鹹壓鑰糧鑰 (製鹹窪製鬱獵顧壓觸蓋 ) 更多	积极	2024-10-01
				BMS-986156+ipilimumab+SABR	鹽醖製襯糧鏇簾憲鹹憲(齋網艱觸觸衊願鑰範廠) = 壓餘鹹鬱繭窪選艱繭築廠願夢簾膚鹹壓鑰糧鑰 (製鹹窪製鬱獵顧壓觸蓋 ) 更多
ASTRO2024	N/A	晚期恶性实体瘤	-	BMS-986156 + Ipilimumab	鏇窪膚鹽鏇簾齋窪簾夢(積製齋壓鏇選夢窪製觸) = 齋積壓夢網鏇積衊簾鑰簾壓廠製衊廠築膚簾鹽 (繭蓋積鏇憲鑰構願網蓋, 4.3 ~ 12.3) 更多	-	2024-10-01
				BMS-986156 + Ipilimumab + SABR	淵鏇襯製壓衊繭衊觸顧(獵獵蓋鬱廠選觸窪顧顧) = 蓋願鬱鏇鹹網憲憲鹹糧範簾構淵齋繭選廠鏇鑰 (壓顧鏇簾衊繭鹹鑰淵夢 ) 更多
NCT02598960 (Pubmed) 人工标引	临床1/2期	实体瘤	292	BMS-986156	-	积极	2020-01-01
				nivolumab+BMS-986156	衊鬱觸鹽膚範鹽夢壓構(壓襯餘廠憲顧憲憲壓顧) = 衊選膚網網壓顧糧衊糧顧壓蓋醖繭齋夢艱淵網 (醖鹽觸齋膚鹽築艱選艱 ) 更多