Pembrolizumab

点击蓝字 关注我们 前言 胆道恶性肿瘤（BTC）起病隐匿、侵袭性高，预后极差。约70%的患者确诊时已为晚期，失去了根治性手术机会。顺铂联合吉西他滨是晚期BTC的标准一线化疗方案，近年来已推荐在此基础上联合度伐利尤单抗或帕博利珠单抗进行免疫治疗。然而，晚期患者一线治疗进展后的二线选择十分有限，尤其是在缺乏可靶向基因改变的情况下，可用的方案（如FOLFOX或基于伊立替康的化疗）疗效较低，难以满足临床需求。因此，开发有效的二线治疗策略至关重要。为此，研究人员对化疗以外的替代策略进行了广泛探索。尽管已有多种药物获批用于治疗携带可靶向基因改变（如IDH1突变、FGFR2融合、HER2过表达）的BTC，但针对非生物标志物筛选人群的治疗一直难以取得突破。近期，西班牙Fundación Jiménez Díaz大学医院Angela Lamarca教授围绕双特异性抗体在BTC中的应用进行了深入探讨，其中CTX-009（Tovecimig）展现出值得关注的潜力。 Angela Lamarca教授 ✓ 双靶并击双特异性抗体Tovecimig在胆道癌二线治疗中崭露头角 在肿瘤治疗领域，双特异性抗体正在引发越来越多的关注。例如，靶向PD-1和VEGF的新型双特异性抗体依沃西单抗已在晚期实体瘤患者中证实了其安全性与有效性，并在BTC中展现出应用前景。此外，Tovecimig是一种在研的双特异性抗体药物，可同时阻断Delta样配体4（DLL4）和血管内皮生长因子A（VEGF-A）的信号通路。其中，VEGF-A在BTC中过表达，并在肿瘤转移和不良预后中发挥作用；而DLL4蛋白作为Notch 1受体的主要配体，可影响Notch信号通路（该通路与胆管癌发生相关）。这两者共同为Tovecimig在BTC中探索提供了一定的理论依据。 Tovecimig的研发始于一项在晚期实体瘤患者中开展的Ⅰ期单药剂量递增研究。该研究共入组45例患者（剂量递增阶段31例，剂量扩展阶段14例）。患者既往接受过多线治疗，中位既往治疗线数为4线。结果显示，未观察到剂量限制性毒性，最常见的≥3级治疗相关不良事件为高血压（15.6%）和贫血（6.7%）。在推荐的Ⅱ期剂量下，总体客观缓解率为18.8%。值得注意的是，研究人员收集了存档肿瘤组织样本，采用免疫组织化学方法评估了DLL4表达水平；所有3例影像学缓解的患者均表现出高DLL4表达。 基于Tovecimig颇具前景的疗效和良好的安全性特征，研究人员探索了其联合策略（联合伊立替康或紫杉醇）在转移性或晚期实体瘤中的效果，并进一步将其与紫杉醇联合用于BTC的研发。一项Ⅱ期研究共纳入24例经治的晚期BTC患者，其中肝内胆管癌9例（37%）、肝外胆管癌3例（13%）、胆囊癌7例（29%）、壶腹部癌5例（21%）。患者接受Tovecimig（10 mg/kg，静脉给药，每两周一次）联合紫杉醇（80 mg/m²，静脉给药，第1、8、15天给药，每4周为一个周期）治疗。结果显示，所有治疗线数的总体客观缓解率为37.5%，其中二线治疗患者的客观缓解率高达63.6%。 目前，正在进行的Ⅱ/Ⅲ期COMPANION-002研究（NCT05506943）旨在评估Tovecimig联合紫杉醇对比紫杉醇单药用于二线治疗晚期BTC患者的疗效和安全性。患者按2:1的比例随机分配至Tovecimig联合紫杉醇组或紫杉醇单药组。研究的主要终点是独立中央放射学审查评估的客观缓解率。值得注意的是，患者入组不依赖于DLL4表达状态。此前公布的初步研究结果表明，在晚期BTC患者中，与紫杉醇单药治疗相比，Tovecimig联合紫杉醇治疗可显著提高总缓解率：联合治疗组为17.1%，而单用紫杉醇组为5.3%（P=0.031），所有缓解均经盲法独立中心放射学评估确认。联合治疗组的疾病进展率也显著低于对照组，分别为16.2%和42.1%，表明联合治疗组在缓解之外还能有效控制疾病进展（表1）。安全性方面，Tovecimig的安全性特征可控，并且与此前该药的临床评估结果一致。根据此前公布的数据，独立数据监查委员会已经4次评估安全性，并认为试验可以按原计划继续进行。 表1. COMPANION-002研究中患者肿瘤缓解情况 值得注意的是，在其他肿瘤类型（如结直肠癌）中，COMPANION-003研究的数据已于近期在2026年美国临床肿瘤学会胃肠道肿瘤研讨会（ASCO GI）上公布。该研究中Tovecimig作为单药使用，客观缓解率显著较低，仅为5%（40例患者中2例缓解）。 ✓ 希望与待解Tovecimig联合化疗在胆道癌二线治疗中的前景与验证需求 Angela Lamarca教授指出，综合现有证据，Tovecimig在BTC中的研究数据令人鼓舞。然而，仍需等待COMPANION-002研究的最终结果，以明确其在BTC中的真正价值。该药的毒性特征支持与化疗联合使用，且鉴于近期在其他消化道肿瘤中单药治疗的低缓解率，联合化疗似乎是必要的。但需要指出的是，紫杉醇在BTC中的常规应用相对有限。因此，如果COMPANION-002研究获得阳性结果，未来还需要开展一项验证性研究，将这一新联合方案与当前标准的二线化疗方案进行头对头比较。此外，为进一步优化该药在BTC中的应用，还应探索基于DLL4表达水平的患者筛选策略。 尽管关于Tovecimig仍存在上述未解问题，但对于确诊为晚期BTC且无可靶向基因改变的患者，二线治疗药物的研发仍是巨大的未被满足的需求。任何有希望的努力都值得欢迎，因为它们为患者打开了新的视野。 参考文献1.https://dailynews.ascopubs.org/do/tovecimig-ctx-009-bispecific-antibody-targeting-dll4-and-vegf-a-perspectives-field2.https://www.globenewswire.com/news-release/2025/04/01/3053162/0/en/Tovecimig-CTX-009-Meets-Primary-Endpoint-in-the-Ongoing-Randomized-Phase-2-3-Study-in-Patients-with-Biliary-Tract-Cancer.html （来源：肿瘤瞭望消化时讯） 声 明 凡署名原创的文章版权属《肿瘤瞭望》所有，欢迎分享、转载。本文仅供医疗卫生专业人士了解最新医药资讯参考使用，不代表本平台观点。该等信息不能以任何方式取代专业的医疗指导，也不应被视为诊疗建议，如果该信息被用于资讯以外的目的，本站及作者不承担相关责任。

Interim analyses show INBRX-106 +pembrolizumab achieved a 44.0% confirmed Objective Response Rate (cORR): 中期分析显示，INBRX-106 + 帕博利珠单抗（pembrolizumab）达到了 44.0% 的确认客观缓解率 (cORR)：In the preliminary confirmed response-evaluable population, the INBRX-106 + pembrolizumab combination achieved a cORR of 44.0% versus 21.4% with pembrolizumab alone, representing a 22.6% absolute increase in cORR. 在初步确认的可评估反应人群中，INBRX-106 + 帕博利珠单抗组合的总体缓解率（cORR）达到了44.0%，而单独使用帕博利珠单抗的总体缓解率为21.4%，绝对提升了22.6%。Superior depth of response: 更优的响应深度： Responding patients in the combination arm demonstrated deeper tumor reductions overall, with the majority achieving target lesion shrinkage exceeding 50%; notably, three patients achieved a complete radiographic response. 联合治疗组的应答患者总体上表现出更显著的肿瘤缩小，大多数患者的靶病灶缩小超过50%；值得注意的是，三名患者达到了完全的影像学缓解。Up to 15-fold mean increase in systemic T-Cell expansion: 系统性T细胞扩增平均增加高达15倍：Peripheral blood analysis showed robust CD8+ and CD4+ T-cell proliferation in combination-treated patients, providing mechanistic support for the observed clinical activity. 外周血分析显示，联合治疗的患者中CD8+和CD4+ T细胞增殖强劲，为观察到的临床活性提供了机制支持。Manageable safety profile: 可控的安全性概况：The combination demonstrated a manageable preliminary safety profile consistent with that expected from an immunotherapy combination. 该组合展示了一个与免疫疗法组合预期相符的可控初步安全特性。SAN DIEGO 圣地亚哥, ，May 11, 2026 2026年5月11日/PRNewswire/ -- Inhibrx Biosciences, Inc. (Nasdaq: /PRNewswire/ -- Inhibrx生物科学公司（纳斯达克：INBX 收件箱) ('Inhibrx' or the 'Company'), a clinical-stage biopharmaceutical company focused on developing novel biologic therapeutic candidates, today announced positive interim results from the randomized, first-line Phase 2 portion of the HexAgon study. The trial evaluated the safety and efficacy of INBRX-106, a hexavalent OX40 agonist, in combination with pembrolizumab (the combination arm) versus pembrolizumab monotherapy (the control arm) in first-line patients with treatment-naïve, PD-L1 positive (CPS ≥ 20) metastatic or unresectable recurrent Head and Neck Squamous Cell Carcinoma (HNSCC).. ）（“Inhibrx”或“公司”），一家处于临床阶段的生物制药公司，专注于开发新型生物治疗候选药物，今天宣布了HexAgon研究随机第一线二期部分的积极中期结果。该试验评估了INBRX-106（一种六价OX40激动剂）与pembrolizumab联合使用（联合组）对比pembrolizumab单药治疗（对照组）在一线治疗中PD-L1阳性（CPS ≥ 20）、未接受过治疗、转移性或不可切除的复发性头颈部鳞状细胞癌（HNSCC）患者中的安全性和有效性。HNSCC was selected as a proof-of-concept indication, as PD-1 monotherapy is active in this tumor type but leaves significant room for improvement. The trial design was modeled after KEYNOTE-048, focusing on patients with high PD-L1 expression (CPS ≥ 20) in order to further sharpen the ability to detect a treatment effect above checkpoint inhibition alone. HNSCC被选为概念验证适应症，因为PD-1单药治疗在此肿瘤类型中具有活性，但仍有显著的改进空间。试验设计参照了KEYNOTE-048，专注于高PD-L1表达（CPS ≥ 20）的患者，以进一步增强检测超越单独检查点抑制治疗效果的能力。A clear signal of added benefit in this study design would support INBRX-106's potential to enhance checkpoint inhibitor efficacy across checkpoint inhibitor-sensitive indications.. 这项研究设计中明确的附加效益信号将支持INBRX-106增强检查点抑制剂在检查点抑制剂敏感适应症中的疗效潜力。The Phase 2 portion of the HexAgon study enrolled 68 patients: 33 randomized to the combination arm and 35 to the control arm. Baseline prognostic factors are largely balanced between both arms and the study is being conducted at over 80 sites in the United States, Europe and Asia. Today, the Company presented preliminary data from 53 patients (25 in the INBRX-106 combination arm and 28 in the control arm) with a data cutoff of May 7, 2026, representing the evaluable population for confirmed response, defined as patients who had either experienced confirmed disease progression or death, or completed at least two on-study tumor assessments. HexAgon研究的第二阶段部分招募了68名患者：33名随机分配到联合治疗组，35名分配到对照组。基线预后因素在两组之间基本平衡，该研究正在美国、欧洲和亚洲的80多个研究中心进行。今天，公司展示了截至2026年5月7日的53名患者（25名在INBRX-106联合治疗组，28名在对照组）的初步数据，这些患者代表了可用于确认反应的可评估人群，定义为经历过确认的疾病进展或死亡，或已完成至少两次在研究期间的肿瘤评估的患者。The remaining 15 patients in the overall population across both arms had not yet reached the maturity threshold for response confirmation or were not evaluable at the time of this data cut and were therefore not included in this analysis. Active unconfirmed responses and ongoing tumor increases/reductions are present in both arms, and these patients are expected to contribute to the final efficacy dataset in a subsequent update.. 总体人群中两个组的其余15名患者尚未达到反应确认的成熟阈值，或在本次数据截止时无法评估，因此未纳入本次分析。两个组中均存在活跃但未确认的反应以及持续的肿瘤增大/缩小，预计这些患者将在后续更新中为最终的疗效数据集做出贡献。In the evaluable population, 11 out of 25 patients (44.0%) in the INBRX-106 combination arm achieved a confirmed objective response, compared with 6 out of 28 patients (21.4%) in the control arm. This represents a 22.6% absolute increase in confirmed responses. Three complete responses were observed in the INBRX-106 combination arm, reflecting tumor clearance, while no complete responses were observed with pembrolizumab alone. 在可评估人群中，INBRX-106联合治疗组的25名患者中有11名（44.0%）获得了确认的客观缓解，而对照组的28名患者中有6名（21.4%）获得确认缓解。这代表确认缓解率绝对提高了22.6%。INBRX-106联合治疗组观察到三例完全缓解，反映了肿瘤清除，而单独使用pembrolizumab时未观察到完全缓解。Complete responses in first-line HNSCC remain uncommon and are generally associated with more durable outcomes.. 一线治疗头颈部鳞状细胞癌（HNSCC）的完全缓解仍然很少见，且通常与更持久的疗效相关。These clinical findings were supported by pharmacodynamic data, which showed up to a 15-fold increase in peripheral CD8+ and CD4+ T-cell proliferation and up to a four-fold increase in activation in INBRX-106 combination-treated patients compared with up to 2.5-fold and 1.5-fold increases, respectively, in those receiving pembrolizumab alone. 这些临床发现得到了药效学数据的支持，数据显示，与单独接受派姆单抗治疗的患者相比，INBRX-106联合治疗的患者外周CD8+和CD4+ T细胞增殖增加了高达15倍，活化增加了高达4倍，而单独使用派姆单抗的患者分别仅增加2.5倍和1.5倍。The observation of robust systemic T-cell expansion and activation in combination-treated patients, alongside the clinical activity observed in this arm, is consistent with the expected mechanism of action of INBRX-106 as a potent T-cell costimulator.. 在联合治疗的患者中观察到强劲的系统性T细胞扩增和激活，同时这一组别中也观察到了临床活性，这与INBRX-106作为一种强效T细胞共刺激剂的预期作用机制是一致的。The combination of INBRX-106 and pembrolizumab was generally manageable, with a safety profile consistent with the addition of an active immunostimulatory agent to checkpoint blockade. The most common treatment-related adverse events were rash, diarrhea, fatigue, and infusion-related reactions, which were predominantly low-grade. INBRX-106与pembrolizumab的组合通常可控，其安全性特征与在检查点阻断中加入一种活性免疫刺激剂相符。最常见的治疗相关不良事件为皮疹、腹泻、疲劳和输注相关反应，大多为低级别。No treatment-related deaths were reported in either arm.. 两组均未报告与治疗相关的死亡。'We are greatly encouraged by these early clinical results,' said Mark Lappe, Chief Executive Officer of Inhibrx. 'These data, coupled with the clear evidence of T-cell expansion and superior depth of response, give us confidence that INBRX-106 could be the first costimulatory agent to fundamentally shift the efficacy ceiling of immunotherapy, and open the door to combinations with new modalities that could be enhanced by OX40 agonism.'. “我们对这些早期临床结果感到非常鼓舞，”Inhibrx首席执行官马克·拉普表示。“这些数据，加上T细胞扩增的明确证据和更深层次的反应效果，使我们相信INBRX-106可能成为首个从根本上提升免疫治疗效力上限的共刺激剂，并为与可通过OX40激动作用增强的新模式的联合应用打开大门。”Next Steps 下一步The progression-free survival data from the Phase 2 portion of the HexAgon study are expected to become available in the fourth quarter of 2026. The Company plans to begin the Phase 3 portion of the HexAgon study during the third quarter of 2026. HexAgon研究第二阶段的无进展生存数据预计将在2026年第四季度公布。公司计划在2026年第三季度开始HexAgon研究的第三阶段。Based on these promising early results, the Company also aims to evaluate INBRX-106 across broader indications to potentially improve the efficacy of checkpoint inhibitors. This strategy includes initiating a study in the perioperative setting in non-small cell lung cancer (NSCLC) later this quarter. 基于这些令人鼓舞的早期结果，该公司还旨在评估 INBRX-106 在更广泛的适应症中的应用，以潜在提高检查点抑制剂的疗效。该策略包括本季度晚些时候在非小细胞肺癌（NSCLC）围手术期启动一项研究。The Company believes OX40 agonism has the greatest potential to drive cure in earlier-stage disease settings, where patients typically retain a more active and responsive immune system. In addition, the Company is beginning to plan for expansion into the front-line metastatic NSCLC setting, with studies expected to begin in 2027. 公司相信，在早期疾病环境中，OX40激动剂最有潜力推动治愈，因为患者通常仍保留更活跃和响应更强的免疫系统。此外，公司正开始计划扩展到一线转移性非小细胞肺癌（NSCLC）领域，预计相关研究将于2027年开始。Outside of combination with checkpoint inhibitors, the Company plans to explore combinations with agents that could benefit from T-cell costimulation, such as vaccines, T-cell engagers, and CAR-Ts.. 除了与检查点抑制剂联合使用外，公司还计划探索与可能受益于T细胞共刺激的药物联合使用，例如疫苗、T细胞接合器和CAR-T疗法。About INBRX-106 关于INBRX-106INBRX-106 is a hexavalent agonist targeting OX40 (CD134), a costimulatory receptor on T-cells. Utilizing Inhibrx's proprietary single-domain antibody (sdAb) platform, INBRX-106 is designed to achieve the high-order receptor clustering necessary for robust T-cell activation and survival, a feat that has eluded traditional bivalent antibody approaches. INBRX-106 是一种六价激动剂，靶向 T 细胞上的共刺激受体 OX40 (CD134)。利用 Inhibrx 专有的单域抗体 (sdAb) 平台，INBRX-106 能够实现高效激活和维持 T 细胞所需的高阶受体簇集，而这是传统二价抗体方法难以实现的。To date, over 175 patients have been treated with INBRX-106.. 迄今为止，已有超过175名患者接受了INBRX-106的治疗。About Inhibrx Biosciences, Inc. 关于Inhibrx生物科学公司Inhibrx Biosciences is a clinical-stage biopharmaceutical company focused on developing a broad pipeline of novel biologic therapeutic candidates. Inhibrx Biosciences utilizes diverse methods of protein engineering to address the specific requirements of complex target and disease biology, including its proprietary protein engineering platforms. Inhibrx生物科学公司是一家临床阶段的生物制药公司，专注于开发广泛的新型生物治疗候选药物管道。Inhibrx生物科学公司利用多种蛋白质工程方法来满足复杂靶标和疾病生物学的具体需求，包括其专有的蛋白质工程平台。Inhibrx Biosciences was incorporated in January 2024 as a direct, wholly-owned subsidiary of Inhibrx, Inc. Prior to the sale of Inhibrx, Inc. and the INBRX-101 program to Sanofi S.A., Inhibrx Biosciences acquired certain corporate infrastructure and other assets and liabilities through a series of internal restructuring transactions effected by Inhibrx, Inc. Inhibrx生物科学公司于2024年1月成立，是Inhibrx公司的直接全资子公司。在Inhibrx公司及INBRX-101项目出售给赛诺菲之前，Inhibrx生物科学公司通过Inhibrx公司实施的一系列内部重组交易，获得了某些企业基础设施及其他资产和负债。Inhibrx, Inc. also completed a distribution to holders of its shares of common stock of 92% of the issued and outstanding shares of Inhibrx Biosciences. Following such transactions, Inhibrx Biosciences' current clinical pipeline of therapeutic candidates includes ozekibart (INBRX-109) and INBRX-106, both of which utilize multivalent formats where the precise valency can be optimized in a target-centric way to mediate what we believe to be the most appropriate agonist function. Inhibrx, Inc. 还向其普通股股东分配了 Inhibrx Biosciences 已发行和流通股份的 92%。在这些交易之后，Inhibrx Biosciences 当前的治疗候选药物临床管线包括 ozekibart（INBRX-109）和 INBRX-106，这两者均采用了多价格式，其中精确的价态可以以目标为中心进行优化，从而实现我们认为最合适的激动剂功能。For more information, please visit . 如需更多信息，请访问 。www.inhibrx.com www.inhibrx.com. 。Forward-Looking Statements 前瞻性声明Inhibrx cautions you that statements contained in this press release regarding matters that are not historical facts are forward-looking statements. These statements are based on Inhibrx's current beliefs and expectations. These forward-looking statements include, but are not limited to, statements regarding: Inhibrx's judgments and beliefs regarding the strength of Inhibrx's pipeline; statements regarding the safety and efficacy of its therapeutic candidate, INBRX-106, based on topline and interim results; the potential for INBRX-106 to be used for the treatment of HNSCC; the clinical development of INBRX-106, including expected enrollment in the expansion cohort, data readouts, regulatory submissions and interactions, and the timing thereof; any presumption that topline, interim or preliminary data will be representative of final data or data in later clinical trials, including data from the remaining 15 patients in the overall population for the Phase 2 trial for INBRX-106 in first-line HNSCC; Inhibrx's plans to evaluate INBRX-106 across broader indications and to explore combinations with other therapies; Inhibrx's plans to expand into the front-line metastatic NSCLC setting, with studies expected to begin in 2027; and Inhibrx's plans to begin the Phase 3 portion of the HexAgon study during the third quarter of 2026. Inhibrx提醒您，本新闻稿中包含的关于非历史事实的陈述为前瞻性声明。这些声明基于Inhibrx当前的信念和期望。这些前瞻性声明包括但不限于以下内容：Inhibrx对其研发管线实力的判断和信念；关于其治疗候选药物INBRX-106的安全性和有效性，基于初步和中期结果的声明；INBRX-106用于治疗头颈部鳞状细胞癌（HNSCC）的潜力；INBRX-106的临床开发进展，包括扩展队列的预期招募、数据读取、监管递交及互动，以及相关时间安排；任何假设认为初步、中期或预试验数据将代表最终数据或后期临床试验的数据，包括INBRX-106一线治疗HNSCC二期试验整体人群中剩余15名患者的数据；Inhibrx计划在更广泛的适应症中评估INBRX-106，并探索与其他疗法的联合应用；Inhibrx计划于2027年进入一线转移性非小细胞肺癌（NSCLC）领域并启动研究；以及Inhibrx计划在2026年第三季度开始HexAgon研究的三期部分。Actual results may differ from those set forth in this press release due to the risks and uncertainties inherent in Inhibrx's business, including, without limitation, risks and uncertainties regarding: topline data may not accurately reflect the complete results of a particular study or trial and remain subject to audit, and final data may differ materially from topline data; the initiation, timing, progress and results of its preclinical studies and cl. 由于Inhibrx业务中固有的风险和不确定性，实际结果可能与此新闻稿中所述的结果不同，这些风险和不确定性包括但不限于：顶线数据可能无法准确反映特定研究或试验的完整结果，并且仍需接受审计，最终数据可能与顶线数据存在重大差异；其临床前研究的启动、时间、进展和结果以及临床试验等。Investor and Media Contact: 投资者和媒体联系人:Kelly Deck, CFO 凯莉·德克，首席财务官[emailprotected] 电子邮件地址858-795-4260 858-795-4260SOURCE Inhibrx Biosciences, Inc. 来源：Inhibrx生物科学公司21 21% %more press release views with 更多新闻发布视图与 Request a Demo 请求演示