Xevinapant(Xevinapant) - 药物靶点：IAP x XIAP x cIAP1 x cIAP1/cIAP2_在研适应症：头颈部肿瘤，淋巴瘤，卵巢上皮癌_专利_临床

概要

基本信息

药物类型

小分子化药

别名

Iap inhibitor at-406、SMAC mimetic、AT 406

+ [5]

靶点

IAP x XIAP x cIAP1 x cIAP1/cIAP2

作用机制

Inhibitors of apoptosis (IAP) protein family inhibitors、XIAP抑制剂(凋亡抑制蛋白-3抑制剂)、cIAP1抑制剂(细胞凋亡抑制蛋白1抑制剂)

治疗领域

肿瘤免疫系统疾病内分泌与代谢疾病+ [2]

在研适应症

头颈部肿瘤淋巴瘤卵巢上皮癌

非在研适应症

急性髓性白血病晚期恶性实体瘤结肠癌+ [12]

原研机构

ASCENTA

在研机构

Merck KGaAASCENTA

Debiopharm International SA

+ [1]

非在研机构

默克雪兰诺（北京）医药研发有限公司FarmeaEMD Serono Research & Development Institute, Inc.

+ [3]

最高研发阶段临床3期

首次获批日期-

最高研发阶段(中国)终止

特殊审评突破性疗法 (美国)

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结构

分子式C32H44ClN5O4

InChIKeyDBXTZCYPHKJCHF-ZZPLZQMBSA-N

CAS号1071992-57-8

关联

23

项与 Xevinapant 相关的临床试验

NCT06463184 / Withdrawn临床1期IIT

A Phase 1, Open-Label Window-of-Opportunity Study to Assess the Pharmacokinetics, Pharmacodynamics and Central Nervous System (CNS) Penetration of Xevinapant in Preoperative Subjects With Recurrent High-Grade Glioma (rHGG)

Researchers will investigate the ability of Xevinapant to cross the blood-brain barrier and exert anti-tumor effects on rHGG through activation of apoptosis. Researchers hypothesize that oral administration of Xevinapant has acceptable safety and tolerability in patients with recurrent HGG and demonstrate pharmacokinetic and pharmacodynamic effects in HGG tumors. To that end, Researchers will engage in a phase I "window of opportunity" translational clinical trial in patients undergoing a clinically-indicated craniotomy for resection of recurrent tumors to evaluate the impact of treatment on rHGG.

开始日期2024-07-22

申办/合作机构

H. Lee Moffitt Cancer Center & Research Institute, Inc.

[+1]

NCT06084845 / Withdrawn临床2期IIT

Phase II Trial of Xevinapant and Chemoradiotherapy in Adjuvant Treatment for Patients With Head and Neck Squamous Cell Carcinoma With High Risk Pathologic Features

This phase II trial compares the effect of usual radiation therapy with cisplatin/carboplatin (chemoradiation) to the addition of xevinapant with chemoradiation in patients with head and neck cancer. Radiation therapy uses high energy x-rays, particles, or radioactive seeds to kill cancer cells and shrink tumors. Cisplatin is in a class of medications known as platinum-containing compounds. It works by killing, stopping or slowing the growth of cancer cells. Carboplatin is in a class of medications known as platinum-containing compounds. It works in a way similar to the anticancer drug cisplatin, but may be better tolerated than cisplatin. Carboplatin works by killing, stopping or slowing the growth of cancer cells. Xevinapant is a first-in-class antagonist of inhibitor of apoptosis (programmed cell death) proteins (IAPs), which leads to tumor cell death and enhances tumor cell sensitivity to chemotherapy and radiotherapy. Giving xevinapant with chemoradiation may be more effective in preventing head and neck cancer from growing or spreading than chemoradiation alone.

开始日期2024-04-12

申办/合作机构

ECOG-ACRIN Medical Research Foundation, Inc.

[+1]

NCT06110195 / Active, not recruiting临床1期IIT

A Phase I Study of Xevinapant With Radiation and Concurrent Carboplatin and Paclitaxel in Patients Ineligible for Cisplatin With Locoregionally Advanced Squamous Cell Carcinoma of the Head and Neck

The goal of this clinical trial is to determine the best safe dose of xevinapant that can be given in combination with chemotherapy and radiation in patients with head and neck cancer. Up to 4 doses of xevinapant will be tested in the dose escalation portion of the study. After the best safe dose is found during escalation, an additional group of participants will be enrolled at that dose to learn more about the treatment combination (dose expansion).
The main question[s] it aims to answer are:
what is the maximum safe dose that can be given
what dose should be used in subsequent (phase 2) trials
Participants will receive xevinapant in combination with paclitaxel and carboplatin chemotherapy and radiation. Treatment will be given in 3-week cycles for 3 cycles.

开始日期2024-01-24

申办/合作机构

The University of Chicago

[+1]

100 项与 Xevinapant 相关的临床结果

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100 项与 Xevinapant 相关的转化医学

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100 项与 Xevinapant 相关的专利（医药）

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391

项与 Xevinapant 相关的文献（医药）

2024-12-01·CELLULAR AND MOLECULAR LIFE SCIENCES

SPOP-mediated RIPK3 destabilization desensitizes LPS/sMAC/zVAD-induced necroptotic cell death

Article

作者: Bang, Geul ; Lee, Cheol-Jung ; Lee, Joo Young ; Jeung, Dohyun ; Kim, Jin Young ; Kim, Kwang Dong ; Kang, Han Chang ; Byun, Jiin ; Lee, Hye Suk ; Lee, Ga-Eun ; Cho, Hana ; Kwon, Young Jik ; Wu, Juan ; Cho, Yong-Yeon ; Chen, Weidong ; Nam, Soo-Bin

Abstract:

RIPK1/RIPK3-MLKL signaling molecules are fundamental in initiating necroptotic cell death, but their roles in the development of colon cancer are unclear. This study reports that RIPK3 interacted with SPOP, a component of the E3 ligase within the Cul3 complex. This interaction leads to K48-linked ubiquitination and subsequent proteasomal degradation of RIPK3. Two distinct degron motifs, PETST and SPTST, were identified within the linker domain of RIPK3 for SPOP. RIPK3 phosphorylations at Thr403 by PIM2 and at Thr412/Ser413 by ERK2 are essential to facilitate its interaction with SPOP. Computational docking studies and immunoprecipitation analyses showed that these PIM2 and ERK2 phosphorylations bolster the stability of the RIPK3-SPOP interaction. In particular, mutations of RIPK3 at the degron motifs extended the half-life of RIPK3 by preventing its phosphorylation and subsequent ubiquitination. The deletion of SPOP, which led to increased stability of the RIPK3 protein, intensified LPS/sMAC/zVAD-induced necroptotic cell death in colon cancer cells. These findings underscore the critical role of the SPOP-mediated RIPK3 stability regulation pathway in controlling necroptotic cell death.

2024-11-22·JCI Insight

HIV-1 latency reversal agent boosting is not limited by opioid use

Article

作者: Corry, Heather ; Lilie, Tyler J. ; Olson, Alex ; Tsibris, Athe ; Taylor, Jessica ; Bouzy, Jennifer ; Lin, Nina ; Coxen, Kendyll ; Asundi, Archana ; Clayton, Kiera ; Lilie, Tyler ; Jordan, Hannah ; Roche, Samantha

Opioid use may affect the HIV-1 reservoir and its reversal from latency. We studied 47 virally suppressed people with HIV (PWH) and observed that lower concentration of HIV-1 latency reversal agents (LRAs), used with small molecules that did not reverse latency, synergistically increased the magnitude of HIV-1 reactivation ex vivo, regardless of opioid use. This LRA boosting, which combined a second mitochondria-derived activator of caspases mimetic or low-dose PKC agonist with histone deacetylase inhibitors, generated more unspliced HIV-1 transcription than PMA with ionomycin (PMAi), the maximal known HIV-1 reactivator. LRA boosting associated with greater histone acetylation, modulated surface activation-induced markers, and altered T cell production of TNF-α, IL-2, and IFN-γ. HIV-1 reservoirs in PWH contained unspliced and polyadenylated virus mRNA, the ratios of which were greater in resting than total CD4+ T cells and corrected to 1:1 with PMAi exposure. We characterized treated suppressed HIV-1 infection as a period of inefficient, not absent, virus transcription. Multiply spliced HIV-1 transcripts and virion production did not consistently increase with LRA boosting, suggesting the presence of a persistent posttranscriptional block. LRA boosting can be leveraged to probe mechanisms of an effective cellular HIV-1 latency reversal program.

2024-10-02·INTERNATIONAL JOURNAL OF RADIATION BIOLOGY

Study on the sensitizing effect of SM-1 combined with irradiation on head and neck squamous cell carcinoma

Article

作者: Xiao, Yan-Tao ; Hou, Wen-Bin ; Wang, Dan-Dan ; Liu, Gai-Ting ; Li, Yi-Liang ; Hu, Tong ; Gou, Wen-Feng ; Zuo, Dai-Ying

PURPOSE:

Head and neck squamous cell carcinoma (HNSCC) is globally prevalent with high recurrence, low survival rate, and poor quality of life for patients. Derived from PAC-1, SM-1 can activate procaspase-3 and induce apoptosis in cancer cells to exert anti-tumor effects. However, the inhibitory effect of SM-1 on HNSCC after combination with radiation are unclear. This study aims to investigate the radiosensitizing effect of SM-1 on HNSCC in vitro and in vivo.

METHODS:

MTT method was used to detect the effect of SM-1 on the viability of HNSCC cell lines (HONE1, HSC-2, and CAL27). The effects of SM-1 combined with radiation on the survival index of HONE1, HSC-2, and CAL27 cell lines were determined by colony formation assay. Flow cytometry was used to investigate the effects of SM-1 and radiation combination on cell apoptosis and cell cycle, and western blot experiments were performed to detect the expression of apoptosis and cell cycle-related proteins. Finally, a xenograft tumor model of CAL27 was established to evaluate the anti-tumor effect of SM-1 combined with radiation in vivo.

RESULTS:

In vitro, SM-1 effectively inhibited the activity of HNSCC cell lines HONE1, HSC-2, and CAL27 cells, and synergistically showed anti-proliferation activity during combined irradiation. Meanwhile, anti-tumor effect of SM-1 on HNSCC was higher than that of Debio1143, and the radiosensitivity of cells was greatly increased. Flow cytometry and western blot analysis showed that SM-1 induced G2/M phase arrest of head and neck squamous cell carcinoma cells via inhibiting the expression of CyclinB1 and CDC2. Moreover, SM-1 activated caspase-3 activity and up-regulated the cleaved form of PARP1 to induce cell apoptosis. In vivo, SM-1 combined irradiation showed a good anti-tumor effect.

CONCLUSION:

SM-1 enhances HNSCC cell radiation sensitivity in vitro and in vivo, supporting its potential as a radiosensitizer for clinical trials in combination with radiotherapy.

100

项与 Xevinapant 相关的新闻（医药）

2024-12-10

·生物谷

破解HIV病毒库的“藏身之地”！iScience：SMAC类似物APG-1387 可在小鼠体内降低HIV病毒库并限制病毒反弹

经过APG-1387治疗后，接受过逆转录病毒药物治疗的受感染小鼠体内的病毒库规模有所缩小。自上世纪80年代初出现以来，艾滋病病毒（HIV）已经扰乱和夺走了无数人的生命。现代疗法虽然帮助许多感染者存活下来，但科学家们仍在努力寻找彻底根除这种病毒的方法。如今，来自加拿大蒙特利尔大学的研究人员发表了一项新的研究，揭示了HIV在体内抵抗治疗的“藏身之地”的弱点，并提出了挫败这些弱点的潜在方法。相关研究结果于2024年11月26日在线发表在iScience期刊上，论文标题为“Bivalent SMAC mimetic APG-1387 reduces HIV reservoirs and limits viral rebound in humanized mice”。想象一下，HIV就像一群狡猾的小偷，它们找到了人体内的安全屋——被称为“病毒库”的细胞，在那里躲过了药物的追捕。这些病毒库对目前的抗逆转录病毒治疗（ART）不敏感，是根除HIV的主要障碍。消除这些病毒库不仅可以防止长期接受治疗的HIV感染者的病毒反弹，还能预防治疗中断后的病情恶化，以及因慢性炎症引发的认知障碍、心血管疾病和某些癌症等并发症。在这场与HIV的长期斗争中，蒙特利尔大学附属蒙特利尔临床研究所人类逆转录病毒学组主任、蒙特利尔大学医学教授Éric Cohen和他的团队一直在探索如何攻破这些病毒库。他们将目光投向了一种用于抗击癌症的分子家族——SMAC类似物（SMAC Mimetic, SM）。Cohen教授解释说，“我们尝试用一种‘激活并杀死’的策略，重新唤醒潜伏的HIV，然后摧毁这些被激活的细胞。” SM分子有两个重要特性： 1. 它能重新激活对转录因子NFkB有反应的基因表达，而不会引起重要的促炎反应。 2. 它能促使那些表达大量细胞凋亡抑制剂的细胞死亡，比如HIV病毒库中的细胞。通过与中国生物制药公司亚盛医药（Ascentage Pharma）合作，研究人员测试了一种名为APG-1387的SM分子，该分子正在肿瘤临床试验中使用。他们在实验室开发的HIV潜伏模型和人源化小鼠体内进行了评估。结果显示，经过APG-1387治疗后，接受过逆转录病毒药物治疗的受感染小鼠体内的病毒库规模有所缩小。更重要的是，在中断抗逆转录病毒治疗后，接受APG-1387治疗的小鼠的病毒反弹减少，且出现的时间推迟，这表明潜伏的病毒库确实减少了。 Cohen教授表示，“这项研究的重要性在于，它证实了这种策略可以在体内发挥作用，而不会产生太多的毒性效应。它还揭示了病毒库固有的弱点，有可能利用这些弱点来消除潜伏的HIV。”他和他的团队现在正计划将这种方法与刺激免疫系统的干预措施结合起来，以更大程度地消除病毒库。（生物谷Bioon.com）参考资料： Jaspreet Jain et al. Bivalent SMAC mimetic APG-1387 reduces HIV reservoirs and limits viral rebound in humanized mice. iScience, 2024, doi:10.1016/j.isci.2024.111470.

临床1期

2024-09-12

·Endpoints

Debiopharm, ITM ink €300M licensing deal for cancer treatment

Debiopharm and ITM announced a licensing deal for a radiopharmaceutical treatment that’s being investigated in several cancers. Debiopharm, which is based in Switzerland, is eligible for upfront, development and regulatory milestone payments of about €300 million, or about $331 million, along with commercial milestones and low double-digit royalties on potential future sales. In exchange, the German radiopharma biotech gets exclusive global development and commercialization rights to Debiopharm’s peptide-based theranostic pair, which is a combination of the therapeutic compound Debio 0228 and diagnostic imaging agent Debio 0328. The combo is currently in the Phase 1/2 GaLuCi trial in clear cell renal cell carcinoma, pancreatic ductal adenocarcinoma and colorectal cancer. According to the companies, the treatment combo targets the carbonic anhydrase IX surface protein, which plays a role in promoting tumor survival, growth and metastasis. “Adding a clinical stage theranostic pair that targets the critical CA IX protein aligns seamlessly with our mission to expand access to innovative radiopharmaceuticals on a global scale,” ITM CEO Andrew Cavey said in a statement. Debiopharm CEO Bertrand Ducrey added in a statement that Debio 0328’s “outstanding potential as a stand-alone imaging agent has also boosted our confidence for the upcoming evaluation of Debio 0228, the therapeutic agent.” Back in June , Merck KGaA decided to wind down Phase 3 trials for a cancer drug called xevinapant that it licensed from Debiopharm in 2021 after a failure.

引进/卖出临床3期多肽偶联药物

2024-08-01

·Insight数据库

默克上半年财报：制药业务收入超 41 亿欧元；肿瘤产品收入增长超 14%

8 月 1 日，德国默克（Merck KGaA）发布了 2024 年第二季度和上半年财报。该集团所有业务净销售额增长 1.7% 至 54 亿欧元。其中，该公司的制药业务（Healthcare）第二季度销售额为 21.37 亿欧元，增长 5.3%；上半年销售额为 41.84 亿欧元，增长 7.6%。报告指出，这一增长主要得益于肿瘤、心血管、代谢和内分泌学领域的收入增长。肿瘤领域肿瘤业务第二季度收入为 4.9 亿欧元，增长 9.2%；上半年收入为 9.9 亿欧元，增长 14.1%。截图来自：默克财报 Erbitux（西妥昔单抗）在肿瘤领域，EGFR 单抗 Erbitux 仍然是默克最畅销的抗癌药物，该药第二季度销售额为 2.76 亿欧元，增长 8.2%；上半年销售额为 5.63 亿欧元，增长13.6%。根据报告，Erbitux 二季度销售额的强劲增长主要得益于欧洲、拉丁美洲和亚太地区的增长。西妥昔单抗是 EGFR 表达、RAS 野生型转移性结直肠癌以及复发性和/或转移性和局部晚期头颈部鳞状细胞癌患者的标准治疗。目前，默克开展了近 200 项涉及西妥昔单抗的活跃临床试验，包括超 15 项 III 期研究。 Bavencio (Avelumab) 抗 PD-L1 抗体 Bavencio 第二季度销售额为 1.86 亿欧元，增长 6.4% ；上半年销售额为 3.72 亿欧元，增长 10.2%。Bavencio 在第二季度的稳健增长主要得益于除北美以外的所有其它地区的收入贡献。 Bavencio 已获准在 70 多个国家/地区作为晚期尿路上皮癌的一线维持治疗。根据 JAVELIN Bladder 100 试验的结果，它已成为治疗这种疾病的标准治疗。Bavencio 还获准与阿昔替尼联合用于晚期肾细胞癌的一线治疗，并且是转移性默克尔细胞癌（一种罕见皮肤癌）的单药疗法的标准治疗。其它肿瘤管线进展默克也披露了该公司肿瘤领域其它产品管线的进展。其中，口服 MET 抑制剂 Tepmetko(Tepotinib) 已在全球约 40 个市场上市，其它市场的监管申请正在审评查中。今年 2 月份，FDA 正式批准了 Tepmetko（此前该药物已获 FDA 加速批准）。今年 6 月，默克宣布停止了 IAP 抑制剂 Xevinapant 的随机 III 期 TrilynX 研究，该研究旨在评估 xevinapant 联合放化疗对未切除局部晚期头颈部鳞状细胞癌 (LA SCCHN) 患者的疗效。xevinapant 的另一项 III 期临床试验 XRay Vision 也已停止，该研究旨在评估 xevinapant 联合放疗对已切除 LA SCCHN 患者的疗效。 2024 年上半年，默克还在 ASCO 年会上以口头报告的形式介绍了抗 CEACAM5 抗体-药物偶联物 (ADC) M9140 在晚期结直肠癌中的 Ia 期研究结果。这是默克开发的第一个进入临床开发的 ADC，目前已进入到结直肠癌的 Ib 期阶段。此外，在 DNA 损伤反应 (DDR) 产品组合中，默克表示将继续推进 ATR 抑制剂 Tuvusertib (M1774) 的开发。该公司正在三项 II 期临床研究中探索 Tuvusertib 的四种组合，涉及适应症包括非鳞状非小细胞肺癌、PARP 抑制剂抗药性卵巢癌、晚期尿路上皮癌。神经病学和免疫学领域神经病学和免疫学产品第二季度销售额为 4.34 亿欧元，下降-7.4%；上半年销售额为 8.53 亿欧元，与去年同期基本持平。截图来自：默克财报在神经病学和免疫学领域，默克目前的产品组合包括两种用于治疗复发性 MS (RMS) 的获批产品 ---- Rebif（干扰素 β-1a）和 Mavenclad（克拉屈滨片）。 Rebif 是一种改善病情的药物，20 多年来一直是 RMS 的标准治疗方法。该药 Q2 销售额为 1.68 亿欧元，下降-18.5% ；上半年销售额为 3.26 亿欧元，下降 -9.0% 。报告指出，Rebif 二季度销售额的下降是由于干扰素市场持续激烈的竞争所致，以及口服剂型和高效 MS 疗法的竞争，预计未来这些因素将会导致该药的销售额进一步下降。 Mavenclad 是一种用于治疗各种形式的高活性 RMS 成人患者的短期口服疗法，已在全球 95 个国家/地区获得批准，包括欧盟、瑞士、澳大利亚、加拿大和美国。该药第二季度销售额为 2.66 亿欧元，增长 1.3% ；上半年销售额为 5.27 亿欧元，增长 6.5% 。除了 MS，默克表示还将继续扩大神经病学和免疫学领域的产品，为医疗需求尚未得到满足的患者开发潜在 first-in-class 疗法。2023 年 6 月，FDA 授予一种用于治疗重症肌无力的口服克拉屈滨（Cladribine）新配方孤儿药资格。默克已于 2024 年 6 月启动了一项全球 III 期临床试验。此外，默克开发的 Enpatoran 是一种 Toll 样受体 7 和 8 (TLR7/8) 抑制剂，处于 II 期临床开发阶段。默克预计 Enpatoran 在皮肤型红斑狼疮和系统性狼疮中的 II 期结果将于 2025 年初公布。心血管、代谢和内分泌学心血管、代谢和内分泌领域产品组合包括 Glucophage、Euthyrox、Concor 和 Saizen 等药物，是默克制药业务部门销售额最大的版块。该领域业务第二季度销售额为 7.46 亿欧元，增长 13.7%；上半年销售额为 14.35 亿欧元，增长 8.9%。截图来自：默克财报 Glucophage 含有活性成分二甲双胍，是治疗 2 型糖尿病的一线药物，在 100 多个国家有售。该药二季度销售额为 2.38 亿欧元，增长 23.5% ；上半年销售额为 4.59 亿欧元，增长 13.8% 。 Concor 含有比索洛尔，它是一种 β 受体阻滞剂，用于治疗高血压和心血管疾病。除了 Concor/Concor Cor，Concor 系列还包括固定剂量组合，例如 Concor Plus/Lodoz（比索洛尔与氢氯噻嗪）。Concor 第二季度销售额为 1.58 亿欧元，增长 13.2% ；上半年销售额为 2.97 亿欧元，增长 7.4%。 Euthyrox 含有活性成分左旋甲状腺素，是治疗甲状腺功能减退症的药物。该药二季度销售额为 1.55 亿欧元，增长 19.2% ；上半年销售额为 2.94 亿欧元，增长 14.1%。 Saizen 含有活性成分生长激素，是默克的主要内分泌产品，用于治疗儿童和成人的多种生长激素紊乱。该药二季度销售额为 9700 万欧元，增长 23.0% ；上半年销售额为 1.86 亿欧元，增长 20%。参考资料：Merck Returns to Organic Sales Growth. https://www.merckgroup.com/en/news/q2-2024-01-08-2024.html 封面来源：企业 Logo 免责声明：本文仅作信息分享，不代表 Insight 立场和观点，也不作治疗方案推荐和介绍。如有需求，请咨询和联系正规医疗机构。编辑：馨药 PR 稿对接：微信 insightxb 投稿：微信 insightxb；邮箱 insight@dxy.cn 多样化功能、可溯源数据…… Insight 数据库网页版等你体验点击阅读原文，立刻解锁！

临床3期财报ASCO会议抗体药物偶联物加速审批

100 项与 Xevinapant 相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
-	-	-	DB16305

研发状态

10 条进展最快的记录,

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适应症	最高研发状态	国家/地区	公司	日期
头颈部鳞状细胞癌	临床3期	中国	默克雪兰诺（北京）医药研发有限公司	2022-10-06
头颈部鳞状细胞癌	临床3期	中国台湾	默克雪兰诺（北京）医药研发有限公司	2022-10-06
头颈部肿瘤	临床3期	美国	Debiopharm International SA	2022-01-30
局部晚期头颈部鳞状细胞癌	临床3期	美国	Merck KGaA	2020-08-07
局部晚期头颈部鳞状细胞癌	临床3期	中国	Merck KGaA	2020-08-07
局部晚期头颈部鳞状细胞癌	临床3期	日本	Merck KGaA	2020-08-07
局部晚期头颈部鳞状细胞癌	临床3期	阿根廷	Merck KGaA	2020-08-07
局部晚期头颈部鳞状细胞癌	临床3期	澳大利亚	Merck KGaA	2020-08-07
局部晚期头颈部鳞状细胞癌	临床3期	奥地利	Merck KGaA	2020-08-07
局部晚期头颈部鳞状细胞癌	临床3期	比利时	Merck KGaA	2020-08-07

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临床结果

适应症

分期

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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


NCT04459715 (TrilynX, BusinessWire) 人工标引	临床3期	局部晚期头颈部鳞状细胞癌	-	xevinapant + CRT	觸繭艱獵蓋襯淵憲構齋(願鹽遞鹽選憲築糧襯鹹) = the trial would be unlikely to meet its primary objective of prolonging event-free survival. 鬱鹽鬱襯壓築憲襯觸齋 (襯繭範鹽簾廠繭簾顧遞 ) 未达到	不佳	2024-06-24
NCT02022098 (ASCO2024) 人工标引	临床2期	头颈部鳞状细胞癌	96	Xevinapant + CRT	夢積窪積築艱顧膚廠選(壓網淵獵艱鬱壓製簾餘) = 餘積獵鑰願艱網遞膚憲簾淵淵窪鏇夢遞獵鬱淵 (簾艱衊築遞網膚築窪糧 ) 更多	积极	2024-05-24
				Placebo + CRT	夢積窪積築艱顧膚廠選(壓網淵獵艱鬱壓製簾餘) = 夢願鑰選製蓋繭構壓遞簾淵淵窪鏇夢遞獵鬱淵 (簾艱衊築遞網膚築窪糧 ) 更多
NCT04122625 (SMARTPLUS-106, CTgov)	临床1/2期	女性生殖器官肿瘤 \| 原发性腹膜癌 \| 实体瘤 ... 更多	46	nivolumab+Debio 1143 (Part A - Debio 1143 150 mg + Nivolumab)	襯餘齋憲衊廠廠構襯選(餘鏇網顧憲選鹹醖構鹹) = 簾餘鑰膚衊鬱顧艱鑰觸鹽憲遞膚齋鬱鬱餘膚廠 (餘膚築構繭糧構廠鏇選, 壓窪夢艱簾鏇艱膚夢繭 ~ 蓋憲製遞糧窪願顧糧簾) 更多	-	2023-06-12
				nivolumab+Debio 1143 (Part A - Debio 1143 200 mg + Nivolumab)	襯餘齋憲衊廠廠構襯選(餘鏇網顧憲選鹹醖構鹹) = 蓋積獵構範憲餘鏇鬱遞鹽憲遞膚齋鬱鬱餘膚廠 (餘膚築構繭糧構廠鏇選, 選醖衊鬱鏇遞艱積蓋衊 ~ 膚鹹積廠壓窪糧憲鹽製) 更多
AACR2023 人工标引	临床1期	非小细胞肺癌	38	xevinapant 200 mg/day+avelumab 10 mg/kg	蓋願鹹膚簾願憲範鬱艱(築鑰餘簾淵顧廠鹹遞蓋) = 窪鏇襯鑰網淵淵願願遞衊網壓範繭壓齋醖憲膚 (艱鬱簾網餘顧鏇築壓鹽, 2.9 ~ 24.8) 更多	不佳	2023-04-14
NCT02022098 (Pubmed)	临床2期	局部晚期头颈部鳞状细胞癌	96	Xevinapant 200 mg/day	鹹選窪襯鬱選築簾鹹蓋(膚艱襯醖繭夢糧鬱築繭) = 夢簾鑰膚築齋範膚範簾艱膚顧壓鹽簾範積醖窪 (構顧鹽築襯齋網憲鹹鑰, 40.3 ~ not evaluable)	积极	2023-04-01
				Placebo	鹹選窪襯鬱選築簾鹹蓋(膚艱襯醖繭夢糧鬱築繭) = 繭窪襯淵淵鬱鹹網顧鹹艱膚顧壓鹽簾範積醖窪 (構顧鹽築襯齋網憲鹹鑰, 21.8 ~ 46.7)
NCT02022098 (ESMO2022) 人工标引	临床2期	局部晚期头颈部鳞状细胞癌 HPV Positive	96	Xevinapant 200 mg+CRT	願簾糧鹹遞觸淵鹽衊鑰(繭壓夢膚糧觸鹽觸膚鑰) = 繭醖顧顧醖糧觸鏇廠鏇簾膚鹹鑰醖齋醖壓積艱 (顧鏇糧獵顧鑰醖製繭糧, 37 ~ 66) 更多	积极	2022-09-10
				Placebo + CRT	願簾糧鹹遞觸淵鹽衊鑰(繭壓夢膚糧觸鹽觸膚鑰) = 淵蓋齋糧積範淵選築範簾膚鹹鑰醖齋醖壓積艱 (顧鏇糧獵顧鑰醖製繭糧, 15 ~ 42) 更多
NCT03871959 (CATRIPCA, ESMO2022) 人工标引	临床1期	结直肠癌 \| 转移性胰腺导管腺癌 MSI-Low	41	Pembrolizumab+Xevinapant (Dose escalation cohort)	觸艱鑰製顧夢淵衊糧簾(淵遞鹹簾蓋鑰糧鑰蓋選) = Xevinapant 200mg/d + pembrolizumab 200mg q3w 齋繭獵獵鹽範壓夢鬱醖 (積範齋繭鑰廠築淵範憲 ) 更多	不佳	2022-09-10
				Pembrolizumab+Xevinapant (PDAC expansion cohort)
NCT02022098 (ESMO2020) 人工标引	临床2期	头颈部鳞状细胞癌	96	Cisplatin+CRT+xevinapant	選遞夢膚顧齋構遞齋選(獵艱艱艱襯構鬱獵衊衊) = 夢糧糧選蓋醖製艱製鏇繭繭襯廠構憲醖積遞鹹 (廠網鹽憲淵壓遞顧積築 ) 更多	积极	2020-09-19
				Cisplatin+CRT+placebo	選遞夢膚顧齋構遞齋選(獵艱艱艱襯構鬱獵衊衊) = 構構獵鹽憲鹽簾構衊窪繭繭襯廠構憲醖積遞鹹 (廠網鹽憲淵壓遞顧積築, 21.8 ~ 46.7) 更多
NCT04122625 (ESMO2020) 人工标引	临床1期	HR阳性/HER2低表达实体瘤	11	Debio 1143+nivolumab (phase Ib)	積艱廠衊糧窪遞鏇遞積(網遞簾淵鹹壓網醖網繭) = Debio 1143 at 200 mg/d + nivolumab 240 mg q2w 糧鹹艱襯衊簾鑰繭糧艱 (餘願選選襯鑰鏇繭醖淵 ) 更多	积极	2020-09-17
NCT02022098 (Pubmed) 人工标引	临床2期	头颈部鳞状细胞癌	48	Debio 1143	膚襯網夢顧窪廠觸憲餘(蓋鑰餘壓簾艱遞鑰鬱襯) = 顧遞鏇憲獵觸醖遞鑰鑰夢餘艱鏇選醖窪築夢顧 (鏇構獵製積觸鬱窪鹹鏇, 39 ~ 69) 更多	积极	2020-09-01
				Placebo	膚襯網夢顧窪廠觸憲餘(蓋鑰餘壓簾艱遞鑰鬱襯) = 觸鏇繭壓淵齋積選餘衊夢餘艱鏇選醖窪築夢顧 (鏇構獵製積觸鬱窪鹹鏇, 20 ~ 48) 更多