An Open Label Trial of BI 765063 in Combination With BI 754091 (Ezabenlimab) Alone or With BI 836880, Chemotherapy, or Cetuximab, in Patients With Recurrent/Metastatic Head and Neck Squamous Cell Carcinoma (HNSCC) or Hepatocellular Carcinoma (HCC)

This study is open to adults with head and neck cancer or liver cancer. This is a study for people for whom previous treatment was not successful or no standard treatment exists. The purpose of this study is to find out whether combining different medicines make tumours shrink in people with head and neck cancer or liver cancer. The tested medicines in this study are antibodies that act in different ways against cancer.
BI 765063 and ezabenlimab may help the immune system fight cancer (checkpoint inhibitors). Cetuximab blocks growth signals and may prevent the tumour from growing. BI 836880 blocks the formation of new blood vessels that the tumour needs to grow. All participants get BI 765063 and ezabenlimab. One group gets no additional medicine. The other groups get either BI 836880, cetuximab, or chemotherapy. BI 765063, ezabenlimab, and BI 836880 are given as infusions into veins every 3 weeks. Cetuximab is given as an infusion every 1 or 2 weeks.
Participants can stay in the study as long as they benefit from treatment and can tolerate it. The doctors monitor the size of the tumour. The doctors also regularly check participants' health and take note of any unwanted effects.

开始日期2022-02-25

申办/合作机构

Boehringer Ingelheim GmbH

NCT04499352 / Withdrawn临床2期

An Open Label, Randomized Phase II Study of BI 754091 Alone or in Combination With BI 836880 in Patients With Chemotherapy Resistant, Unresectable, Metastatic Squamous Cell Carcinoma of the Anal Canal

The objective of this trial is to assess anti-tumour activity of BI 754091 as monotherapy and of BI 754091 in combination with BI 836880 in patients with unresectable or metastatic squamous cell carcinoma of the anal canal who progressed on or after chemotherapy.

开始日期2020-09-14

申办/合作机构

Boehringer Ingelheim GmbH

NCT03861234 / Completed临床1/2期

Safety, Tolerability and Pharmacodynamics of Single Rising Intravitreal and Multiple Rising Intravitreal Doses of BI 836880 in Patients With wAMD (Open Label, Non-randomized, Uncontrolled).

This is a study in people with an eye disease called wet age-related macular degeneration (wAMD). The purpose of the study is to find out how well different doses of a medicine called BI 836880 are tolerated.
People can participate if they are at least 55 years old and if they have new blood vessels in their eyes despite treatment (anti-VEGF therapies). The study has 2 parts. In the first part, people get only 1 dose of BI 836880. This part takes 6 weeks. In the second part, people get 3 times the same dose of BI 836880. This part takes 6 months. BI 836880 is injected into the eye. During the entire study doctors regularly check the health of the participants.

开始日期2019-06-27

申办/合作机构

Boehringer Ingelheim GmbH

100 项与 BI-836880 相关的临床结果

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100 项与 BI-836880 相关的转化医学

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100 项与 BI-836880 相关的专利（医药）

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项与 BI-836880 相关的文献（医药）

2023-10-01·Investigational new drugs

Preclinical evaluation of the VEGF/Ang2 bispecific nanobody BI 836880 in nasopharyngeal carcinoma models.

Article

作者: Lam, Rachel C T ; Wong, C H ; Tsang, Anna C M ; Ma, Brigette B Y ; Chan, Anthony T C ; Hui, Edwin P ; Hui, Connie W C ; Lo, K W

Epstein-Barr virus (EBV)-associated nasopharyngeal carcinoma (NPC) is endemic to parts of Asia and overexpression of vascular endothelial growth factor (VEGF) and hypoxia-inducible factor-1α are common in NPC. Anti-vascular agents have known clinical activity in patients with recurrent/ metastatic NPC and in this study, we investigated the anti-tumor effect of BI 836880, a humanized bispecific nanobody against VEGF and angiopoietin-2 (Ang2), in preclinical models of EBV-positive and EBV-negative NPC. The efficacy of BI 836880 was also compared with bevacizumab, a recombinant humanized monoclonal antibody against VEGF. We found that BI 836880 could exert growth-inhibitory effect on endothelial cells (HUVEC-C) and the EBV-negative NPC cell line (HK1), but to a lesser extent in the EBV-positive NPC cell lines, C17C and C666-1. In patients-derived xenograft (PDX) models of NPC - Xeno-2117 and Xeno-666, BI 836880 could suppress tumor growth and Ki67, as well as induce tumor necrosis and reduce microvessel density. Moreover, treatment with BI 836880 increased the level of macrophage infiltration in both PDX tumor models of NPC, suggesting that BI 836880 may exert immunomodulatory effect on the NPC immune microenvironment. When compared with bevacizumab, BI 836880 appeared to show at least comparable activity as bevacizumab in terms of its anti-proliferative and anti-angiogenic effects. This study showed that BI 836880 has anti-proliferative, anti-angiogenic and possibly immunomodulatory effect in clinical models of NPC, therefore the dual targeting of VEGF and Ang2 signaling in NPC should be further investigated.

2023-06-01·Cancer chemotherapy and pharmacology

Phase I study of the VEGF/Ang-2 inhibitor BI 836880 alone or combined with the anti-programmed cell death protein-1 antibody ezabenlimab in Japanese patients with advanced solid tumors.

Article

作者: Sarashina, Akiko ; Kawakami, Takeshi ; Koyama, Takafumi ; Shimizu, Toshio ; Hou, Jianrui ; Erzen, Damijan ; Yamamoto, Noboru ; Yamazaki, Kentaro ; Li, Bin ; Todaka, Akiko

PURPOSE:

This two-part, open-label, non-randomized dose-escalation study aimed to define the maximum tolerated dose (MTD) of BI 836880 (humanized bispecific nanobody® targeting vascular endothelial growth factor and angiopoietin-2) as monotherapy and in combination with ezabenlimab (programmed death protein-1 inhibitor) in Japanese patients with advanced and/or metastatic solid tumors.

METHODS:

In part 1, patients received an intravenous infusion of BI 836880 at 360 or 720 mg every 3 weeks (Q3W). In part 2, patients received BI 836880 at doses of 120, 360, or 720 mg in combination with ezabenlimab 240 mg Q3W. The primary endpoints were the MTD and the recommended phase II dose (RP2D) of BI 836880 as monotherapy and in combination with ezabenlimab, based on dose-limiting toxicities (DLTs) during the first cycle.

RESULTS:

Twenty-one patients were treated; nine in part 1 and 12 in part 2. No DLTs were reported in either part and the MTD was not reached. The RP2Ds were BI 836880 720 mg Q3W as monotherapy and BI 836880 720 mg plus ezabenlimab 240 mg Q3W. The most common adverse events were hypertension and proteinuria (33.3%) with BI 836880 monotherapy and diarrhea (41.7%) with the combination. Four patients (44.4%) in part 1 had stable disease as best overall tumor response. In part 2, two patients (16.7%) had confirmed partial responses and five had stable disease (41.7%).

CONCLUSION:

MTD was not reached. BI 836880 alone and in combination with ezabenlimab had a manageable safety profile with preliminary clinical activity in Japanese patients with advanced solid tumors.

TRIAL REGISTRATION AND DATE:

NCT03972150, registered on June 3, 2019.

2023-03-01·Journal of Pharmacology and Experimental Therapeutics

Pharmacodynamic and Antitumor Activity of BI 836880, a Dual Vascular Endothelial Growth Factor and Angiopoietin 2 Inhibitor, Alone and Combined with Programmed Cell Death Protein-1 Inhibition

Article

作者: Depla, Erik ; Gschwind, Andreas ; Baum, Anke ; Hilberg, Frank ; Hofmann, Irmgard ; Künkele, Klaus-Peter ; Kraut, Norbert ; Budano, Nicole ; Hofmann, Marco H ; Trapani, Francesca ; Ebner, Florian ; Boucneau, Joachim ; Sykora, Martina ; Aichinger, Martin ; Reichel-Voda, Claudia ; Schweifer, Norbert ; Ehrensperger, Diane

Vascular endothelial growth factor (VEGF) and angiopoietin (ANG)-2 have complementary roles in angiogenesis and promote an immunosuppressive tumor microenvironment. It is anticipated that the combination of VEGF and ANG2 blockade could provide superior activity to the blockade of either pathway alone and that the addition of VEGF/ANG2 inhibition to an anti-programmed cell death protein-1 (PD-1) antibody could change the tumor microenvironment to support T-cell-mediated tumor cytotoxicity. Here, we describe the pharmacologic and antitumor activity of BI 836880, a humanized bispecific nanobody comprising two single-variable domains blocking VEGF and ANG2, and an additional module for half-life extension in vivo. BI 836880 demonstrated high affinity and selectivity for human VEGF-A and ANG2, resulting in inhibition of the downstream signaling of VEGF/ANG2 and a decrease in endothelial cell proliferation and survival. In vivo, BI 836880 exhibited significant antitumor activity in all patient-derived xenograft models tested, showing significantly greater tumor growth inhibition (TGI) than bevacizumab (VEGF inhibition) and AMG386 (ANG1/2 inhibition) in a range of models. In a Lewis lung carcinoma syngeneic tumor model, the combination of PD-1 inhibition with VEGF inhibition showed superior efficacy versus the blockade of either pathway alone. TGI was further increased with the addition of ANG2 inhibition to VEGF/PD-1 blockade. VEGF/ANG2 inhibition had a strong antiangiogenic effect. Our data suggest that the blockade of VEGF and ANG2 with BI 836880 may offer improved antitumor activity versus the blockade of either pathway alone and that combining VEGF/ANG2 inhibition with PD-1 blockade can further enhance antitumor effects. SIGNIFICANCE STATEMENT: Vascular endothelial growth factor (VEGF) and angiopoietin (ANG)-2 play key roles in angiogenesis and have an immunosuppressive effect in the tumor microenvironment. This study shows that BI 836880, a bispecific nanobody targeting VEGF and ANG2, demonstrates substantial antitumor activity in preclinical models. Combining VEGF/ANG2 inhibition with the blockade of the PD-1 pathway can further improve antitumor activity.

项与 BI-836880 相关的新闻（医药）

2024-03-26

·行舟Drug

双特异性抗体癌症治疗

点击上方的行舟Drug ▲ 添加关注前言迄今为止，与传统的抗癌治疗策略相比，免疫治疗被认为是最有前景的全身性肿瘤治疗方法，其中，单克隆抗体因其特异性靶向分子的能力，已成为癌症治疗中一种关键而有效的治疗方式。然而，由于肿瘤复杂的疾病发病机制，针对单一靶点的单克隆抗体往往不足以表现出足够的治疗效果。因此，针对多个靶点的双特异性抗体（bsAbs）应运而生，它的发展改变了肿瘤免疫治疗的领域。目前，人们正在研究越来越多的针对癌症治疗的不同类型的bsAbs。这些类型包括双靶向抑制剂，其作用于不同水平的肿瘤增殖、血管形成和转移；以及双特异性抗体偶联药物、T细胞结合器、双特异性自然杀伤细胞接合器（NKCE）和先天免疫细胞接合器。其他类型还包括双特异性免疫检查点抑制剂（CPI）、共刺激bsAbs和融合蛋白、具有联合检查点抑制和共刺激特征的bsAbs、在肿瘤微环境（TME）中特异性激活的bsAb，以及将过继T细胞治疗和治疗性抗体相结合的新方法。目前，有300多项临床试验涉及200多种不同的双特异性抗体分子，其中约75%用于治疗实体瘤，25%用于治疗血液系统恶性肿瘤。有10种bsAb药物已被批准用于癌症治疗，其中9种在美国和/或欧洲获得批准，cadonilimab在中国获得批准。到目前为止，临床中开发的很大一部分bsAbs已经处于后期阶段（II期和III期）。另外，可以发现，治疗实体瘤的bsAbs主要由免疫调节剂主导，包括双CPI（约45%）和TCE（约33%），其次是靶向双途径、ICEs和ADC的bsAb。bsAb的发展史BsAbs最初的概念是由AlfredNisonof在20世纪60年代首次提出的。他将两个不同的抗原结合位点结合在一个分子中，并从抗牛γ球蛋白和抗卵清蛋白单价片段的混合物中获得了一个具有双重特异性的F(ab’)2分子。1975年，Köhler和Milstein发明了杂交瘤技术，最终解决了生产单克隆抗体的问题，开启了单克隆抗体治疗的新时代。1983年，Milstein和Cuello开创了quadroma技术，该技术基于分泌Abs混合物的两种不同杂交瘤细胞系的体细胞融合，包括具有双重特异性的鼠IgG形式的bsAb。然而，bsAb的低产率以及难以从密切相关的错配副产物中纯化所需的Ab是一个重大问题。1988年，James Huston和他的同事发明了单链抗体片段（scFv），它最大限度地减少了复性问题，例如不正确的结构域配对或聚集。1996年，Genentech的科学家们利用重组DNA技术发明了knob-into-hole技术，克服了Quadrome技术的局限性。通过在人类IgG的CH3结构域之间的界面突变选定的氨基酸，可以减少IgG重链的错配。这种技术利用更有利的蛋白质相互作用，最终可以形成高达90%的正确双特异性重链配对。随后，随着抗体工程和生物学的进展，bsAb的不同概念和结构正在不断演变。靶向双受体抑制的bsAb许多参与细胞信号传导的细胞表面蛋白，如RTK和相关受体，是基于抗体治疗的有效靶点。尽管靶向一个确定的信号受体的抗体治疗是非常有效的，但疾病相关表型通常由不止一种途径触发。这种冗余允许细胞通过使用其他补偿信号通路，从而耐受药物的生长抑制或细胞毒性诱导。同时调节不同疾病相关信号受体或通路的bsAbs可以减少或克服这一限制。Amivantamab（JNJ-61186372）靶向EGFR和肝细胞生长因子受体（MET），两种受体都能触发非小细胞肺癌（NSCLC）的增殖。因此，阻断两种受体比仅阻断一种途径能够更有效地抑制NSCLC的生长。Amivantamab已被FDA批准用于治疗携带EGFR外显子20插入突变的NSCLC亚型。一项随机III期研究的数据显示，在这部分患者中，与单独化疗相比，Amivantamab联合化疗具有显著优越性。另外一些针对肿瘤不同第二靶点的EGFR的bsAbs也正在临床开发中。例如，petosemtamab（MCLA-158）靶向EGFR和LGR5，LGR5是一种癌症干细胞相关的细胞表面受体。Petosemtamab目前正在包括晚期头颈部鳞状细胞癌在内的实体瘤患者的I/II期试验中进行评估（NCT03526835）。靶向配体受体抑制的bsAbbsAbs可以同时阻断两种不同的配体，或者是配体和受体的组合。VEGF和血管生成素2（ANG2）的双重靶向作用分别阻断VEGFR和血管生成因子1受体（TIE2）的激活，这两种途径涉及血管生成。vanucizumab，一种靶向VEGFA和ANG2的bsAb，在临床前模型中与化疗联合显示出抗肿瘤、抗血管生成和抗转移作用。BI836880是一种三特异性纳米抗体融合蛋白，由三个靶向VEGFA、ANG2和HSA的纳米抗体组成，后者可延长其血清半衰期。目前正在头颈部鳞状细胞癌、NSCLC和其他实体瘤患者的I期研究中进行评估。此外，靶向VEGF可以进一步设计成联合靶向肿瘤细胞上的PD-L1或T细胞上的PD-1，从而将抗血管生成与肿瘤免疫学方法联系起来。例如靶向PD1和VEGF的ivonescimab（AK112），其目前已在中国获批用于。其他bsAbs靶向PDL1和VEGF，包括PM8002，该药物正在NSCLC患者的II/III期研究（NCT05756972）中进行评估。靶向受体激活的bsAb许多抗肿瘤反应是通过激活细胞表面受体介导的，包括通过诱导细胞凋亡的免疫反应或细胞死亡。其中一种方法是靶向递送受体激活配体，如生长因子、细胞因子和（共）免疫刺激配体，将其融合到抗体或抗体片段中，以诱导局部或组织特异性激动活性，从而诱导细胞反应。越来越多的这种抗体-配体融合蛋白正在进入临床试验。受体激活也可以使用激动性抗体来实现。针对靶抗原和肿瘤坏死因子超家族（TNFRSF）成员的bsAbs已被证明是具有强大活性和肿瘤选择性的激动分子。RG7386（RO6874813）是一种四价bsAb，靶向癌症相关成纤维细胞上的FAPα和DR5，在具有FAPα间质表达的小鼠模型中具有效和选择性的肿瘤细胞杀伤，并已进入临床测试。此外，BI905711，一种靶向DR5和CDH17的四价双特异性IgG-scFv融合蛋白，目前处于I期临床研究中。靶向递送有效载荷的bsAb存在两种概念上不同的方法来利用bsAbs靶向递送有效载荷，如细胞毒性药物或放射性药物。第一种方法，预靶向治疗，使用bsAb的一个臂特异性靶向肿瘤细胞，另一个臂随后捕获有效载荷到肿瘤细胞。GD2 x DOTA是一种识别GD2的bsAb，并捕获放射性有效载荷177Lu-DOTA，其在TME中组装。在没有四聚化的情况下，由于半衰期，它会被迅速从外围清除。然而，到目前为止，临床试验中很少有bsAbs利用这种MoA，这可能是因为放射性预靶向涉及复杂的导流，限制了其普遍适用性。第二种方法通过递送偶联到双特异性抗体上的细胞毒性有效载荷，实现肿瘤细胞的特异性靶向。目前，bsADC已成为肿瘤药物开发的热点，已有多款bsADC进入临床开发，如ZW49、REGN5093、BL-B01D1等。靶向癌症免疫治疗的bsAb癌症免疫疗法中使用的大多数bsAbs通过T细胞驱动的天然或内源性免疫发挥作用，包括免疫检查点抑制（CPIs）效应细胞接合器（包括TCE和ICEs）以及共刺激性bsAb。双免疫检查点抑制许多抑制免疫检查点的单特异性抗体，如CTLA4或PD-1/PDL-1，已被批准用于癌症免疫疗法。将检查点抑制性抗体疗法扩展到bsAbs可以减少不期望的副作用，并增强疗效。大多数双免疫检查点抑制剂靶向PD-1/PD-L1轴和其他免疫抑制分子，如CTLA-4、TIM-3、LAG-3或TIGIT。MEDI5752（PD-1×CTLA-4）抑制PD-1+激活的T细胞中CTLA-4的功能，诱导PD-1的快速内化和降解。与PD-1和CTLA-4单抗联合治疗相比，MEDI5752的活性显著增强。针对其他检查点分子的双功能性抑制剂，包括LAG-3和TIGIT，也正在开发中。效应细胞接合器细胞接合器连接两种不同类型的细胞，主要是肿瘤细胞和T/NK细胞，以诱导肿瘤细胞溶解。细胞接合器由TAA靶向部分和效应细胞识别部分组成，并进一步分为T细胞接受器和NK细胞接受器。T细胞接合器利用TAA和TCR成分（主要是CD3），它们连接肿瘤细胞和T细胞，绕过TCR-MHC-I相互作用。因此，无论抗原特异性如何，T细胞结合器都会触发T细胞活化，产生包括穿孔素和颗粒酶在内的细胞毒性分子，以杀伤肿瘤细胞。BiTE是T细胞结合器的一种形式，通过靶向TAA和CD3的单链抗体将肿瘤细胞和T细胞结合，用于T细胞介导的肿瘤细胞杀伤。靶向CD19和CD3的blinatumomab是临床上典型的BiTE，2014年，blinatumomab成为第一个被FDA批准的BsAb，用于治疗ALL患者，在随后的几年里，blinatumomab的治疗范围进一步拓宽，2018年，FDA批准其用于首次或第二次完全缓解后MRD≥0.1%的pre-B ALL患者群体的治疗。目前，超过60例BiTE形式的双抗正在进行I/II期临床试验。NK细胞接合器将CD16A+NK细胞重定向至肿瘤细胞，诱导NK细胞活化。与BiTE相比，NK细胞接受者表现出较少的不良反应，如细胞因子释放综合征（CRS）和神经毒性。多种细胞毒性受体可激活NK细胞：CD16（FcγRIII）、天然细胞毒性受体（NCR；NKp30、NKp44、NKp46）、C型凝集素样受体NKG2D（CD314）和CD94/NKG2C。最近，抗CD30×CD16A的NK细胞接合器（AFM13）在AACR 2022的报告中展示了不俗的抗肿瘤效果。共刺激bsAbs高效、持久和局部受限的抗肿瘤免疫反应需要共刺激和共抑制信号来严格调节细胞毒性T细胞、自然杀伤细胞和巨噬细胞的激活、分化和维持。TNFRSF家族的成员（如4-1BB、CD40、OX40、GITR、CD27或CD30）以及CD28免疫球蛋白超家族（如CD28、CTLA4、PD-1、ICOS、BTLA)及其相应的配体在介导免疫调节信号中发挥着重要作用。靶向这些免疫调节途径可以增强免疫治疗。PRS-343（cinrebafusp），是一种针对HER2和4-1BB的四价bsAb，在IND研究中其耐受性良好，没有明显和相关的药物相关毒性；在接受有效剂量治疗的患者中（n=33），12%的患者达到ORR，包括1个CR，疾病控制率（DCR）为52%。bsAbs中通过4-1BB进行肿瘤选择性共刺激的其他靶点还包括EGFR、PSMA、CLDN18.2、B7H4、CEACAM5、HER2、PD-L1和FAP。此外，十多种针对PD-L1和4-1BB的不同bsAbs处于I期或II期试验中。bsAb的新概念bsAbs的领域仍在进一步探索和扩展技术和应用，可能提供目前正在开发的bsAb尚未解决的治疗概念。三特异性TCE共刺激信号可以与双特异性TCE组合以促进更加有效的T细胞活化。这样的三特异性TCE目前正在针对TAA和CD3的临床试验中，并且进一步包含抗CD28结合位点。SAR443216是一种针对HER2×CD3×CD28的三特异性抗体，能够强力激活CD4+和CD8+T细胞，诱导T细胞增殖、细胞因子和颗粒酶B的释放，以及T细胞介导的对表达HER2的肿瘤细胞的杀伤，其目前处于I期临床研究中。在类似的方法中，SAR442257是另一种CD38×CD3×CD28的三特异性抗体。前药方法一种新兴的方法是在肿瘤处选择性激活的前药，产生具有高度肿瘤特异性功能的bsAbs。前药转化为功能性bsAbs可以通过环境触发因素如肿瘤相关蛋白酶来实现。双重肿瘤靶向的另一种前药方法依赖于来自两个具有分裂CD3ε结合部分的肿瘤特异性组装。这些分子需要被设计为非活性的独立实体并在循环中，使得它们仅在肿瘤抗原结合和随后的原位组装时被激活。PROTAC bsAbs另一个新兴概念和新的MoA利用bsAbs通过靶向降解来抑制增殖相关过程。类似于双特异性或多特异性小分子蛋白水解靶向嵌合体（PROTACs），bsAbs可被设计为触发参与癌症发展或进展的表面蛋白的内化和随后的降解。这样的bsAbs同时与靶向降解的蛋白质和降解的因子结合，并触发内化，如膜上的E3泛素连接酶或转铁蛋白受体。目前，抗体-PROTAC概念仍处于早期开发阶段，迄今为止还没有进入临床研究。bsAb递送bsAb开发中另一个重要的新兴概念是bsAb的局部产生和随后的局部递送，如通过脂质纳米颗粒介导的mRNA递送的CLDN6 TCE、溶瘤病毒或包括CAR-T细胞在内的基因治疗方法。细胞因子模拟抗体最后，bsAbs也可以作为细胞因子模拟物或所谓的合成细胞因子激动剂。scFvs或基于单域抗体VHH的方法可以通过模拟IL-2或IL-15、IL-18、I型干扰素和IL-10来有效地触发细胞因子信号传导。这种基于抗体的细胞因子模拟物可能在癌症免疫疗法中具有各种应用。小结bsAbs领域最近取得了实质性进展，到2023年底，已有十几种bsAbs获得批准，许多不同的方法正在临床上进行测试。尽管如此，由于癌症的异质性和适应性，这些方法中的任何一种都不太可能成为普遍的癌症免疫疗法。相反，抗体需要针对某些应用量身定制，并将依赖于与其他方法的结合，以最大限度地提高其疗效和安全性。在不久的将来，多特异性抗体疗法的发展可能会在以下四个领域出现增长：针对具有明确依赖性的肿瘤相关RTK的bsAbs；用于以增加的选择性靶向肿瘤的bsADC；用于靶向降解适用于各种途径的细胞表面蛋白的双特异性PROTAC；以及用于癌症免疫疗法的多特异性抗体。与其他治疗癌症的药物一样，通过改进的诊断方法和新的开发模式，将bsAbs和多特异性抗体疗法应用于早期患者，对于实现治愈癌症患者的目标至关重要。参考文献：1. The present and future of bispecific antibodies for cancer therapy. Nat Rev Drug Discov.2024 Mar 6.2. Development of Bispecific Antibody for CancerImmunotherapy: Focus on T Cell Engaging Antibody. Immune Netw. 2022 Feb; 22(1): e4.文章信息源于公众号小药说药，登载该文章目的为更广泛的传递行业信息，不代表赞同其观点或对其真实性负责。文章版权归原作者及原出处所有，文章内容仅供参考。本网拥有对此声明的最终解释权，若无意侵犯版权，请联系小编删除。学如逆水行舟，不进则退；心似平原走马，易放难收。行舟Drug每日更新欢迎订阅+医药大数据|行业动态|政策解读

免疫疗法临床2期细胞疗法临床结果引进/卖出

2024-02-28

·Pharmaceutical Technology

AbbVie licenses OSE’s chronic inflammation therapy for $48m upfront

OSE-230 is a ChemR23, a G-Protein coupled receptor (GPCR) targeting monoclonal antibody. Image Credit: Poetra.RH / Shutterstock. AbbVie has signed a partnership and licensing agreement with OSE Immunotherapeutics for the latter’s monoclonal antibody OSE-230 in a deal worth up to $713m. OSE-230 is a monoclonal antibody that targets ChemR23, a G-Protein coupled receptor (GPCR). The therapy can potentially resolve chronic inflammation and modulate the function of macrophages and neutrophils. It is currently in preclinical development. Following the news, OSE’s stock was up by more than 55% in trading today. The French pharmaceutical company’s market cap stands at $111.2m. Under the collaboration agreement, AbbVie will pay $48m in upfront payment for the exclusive global licence of the therapy. OSE will also be in line to receive up to $665m in milestone-based payments along with tiered royalties on net sales. OSE has a pipeline of multiple monoclonal antibody candidates that it is developing in collaboration with other pharmaceutical companies. The company is developing two signal regulatory protein α (SIRPα) targeting monoclonal antibodies—BI 765063/ OSE-172 and BI 770371—in collaboration with Boehringer Ingelheim. See Also: NHS expedites availability of Belumosudil for chronic GVHD Beacon Therapeutics unveils promising interim results for gene therapy AGTC-501 BI 765063 is being evaluated as a combination therapy with different cancer therapies such as Boehringer’s ezabenlimab, BI 836880, chemotherapy, and Eli Lilly’s Erbitux (cetuximab) in a Phase I trial (NCT05249426). BI 770371 is being evaluated as a monotherapy and in combination with a PD1 inhibitor, BI 754091, in an international Phase I dose escalation and expansion trial (NCT05327946) in patients with solid tumours. OSE is also developing an anti-CD28 selective monoclonal antibody FR104/VEL-101 in partnership with Denmark-based Veloxis Pharmaceuticals. It is being researched as a treatment to help prevent organ rejection in people who have had a kidney transplant. In February 2022, the therapy received a fast track designation by the FDA for prophylaxis against transplant rejection. Veloxis is planning Phase II trials for the subcutaneous therapy. AbbVie has also made recent investments related to antibody therapies. In December 2023, it partnered with BigHat Biosciences to identify and develop antibody therapies in oncology and neuroscience indications. On a larger scale, in November 2023, AbbVie announced a $10.1bn ImmunoGen acquisition deal . The antibody-drug conjugate (ADC) Elahere (mirvetuximab soravtansine-gynx) was a central part of the deal. The therapy was granted priority review by the US Food and Drug Administration with a Prescription Drug User Fee Act (PDUFA) action date of 5 April 2024.

临床1期引进/卖出优先审批快速通道抗体药物偶联物

2024-01-22

·Pharmaceutical Technology

OSE shares pipeline updates and plans Phase III trial for Tedopi

OSE’s Tedopi is a neoepitope-based immunotherapy activating tumour-specific T-cell cancer vaccine. Image Credit: Gorodenkoff / Shutterstock. The French company OSE Immunotherapeutics has provided an update for its clinical pipeline, with plans to start a confirmatory Phase III study for its cancer vaccineTedopi in the US in Q2 2024. The company has received positive recommendations from the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA) based on the positive data from the Phase III trial (NCT02654587) evaluating Tedopi as a second or third-line therapy in patients with advanced non-small cell lung cancer patients following treatment failure with immune checkpoint inhibitors (ICI). Additionally, OSE is seeking approval from the FDA to validate the companion diagnostic test for Tedopi, developed by Genome Diagnostics. Tedopi is a neoepitope-based immunotherapy activating tumour-specific T-cell cancer vaccine. Apart from the Phase III trial, OSE is also conducting three Phase II trials evaluating Tedopi as a combination therapy in solid tumours such as pancreatic, ovarian and lung cancers. The results from the Phase II trial of Tedopi in combination with chemotherapy in pancreatic cancer patients are expected this year. Data from the Phase II trials (NCT04713514 and NCT03806309) for Tedopi in combination with MSD’s Keytruda (pembrolizumab) and Bristol Myers Squibb ’s Opdivo (nivolumab), respectively, is expected in 2025. OSE’s ulcerative colitis therapy lusvertikimab (OSE-127) is being investigated in a Phase II placebo-controlled trial (NCT04882007). The recruitment for the trial is expected to be completed in Q1 of this year, with initial results expected by mid-2024, as per a 19 January press release. The interleukin (IL)-7 receptor antagonist is also being evaluated in preclinical studies as a treatment for acute lymphoblastic leukaemia (ALL). In July 2023, OSE received a positive opinion on Orphan Drug Designation for lusvertikimab for the treatment of ALL by the EMA. OSE-279 is a programmed cell death 1 (PD-1) inhibiting monoclonal antibody. It is being evaluated as a treatment for solid tumours or lymphomas in a dose-finding and expansion Phase I trial (NCT05751798). OSE is also developing two monoclonal antibodies against signal regulatory protein α (SIRPα), BI 765063/ OSE-172 and BI 770371, in collaboration with Boehringer Ingelheim. BI 765063 is being evaluated as a combination therapy with different cancer therapies such as Boehringer’s ezabenlimab, BI 836880, chemotherapy and Eli Lilly’s Erbitux (cetuximab) in a Phase I trial (NCT05249426). BI 770371 is being evaluated as a monotherapy and in combination with a PD1 inhibitor, BI 754091, in an international Phase I dose escalation and expansion trial (NCT05327946) in patients with solid tumours. OSE is advancing the anti-CD28 selective monoclonal antibody FR104/VEL-101 in partnership with Denmark-based Veloxis Pharmaceuticals. It is researched as a treatment to help prevent organ rejection in people who have had a kidney transplant. In February 2022, the therapy received a fast track designation by the FDA for prophylaxis against transplant rejection. Veloxis is planning Phase II trials for the subcutaneous therapy.

临床3期临床结果临床2期临床1期快速通道

100 项与 BI-836880 相关的药物交易

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研发状态

适应症	最高研发状态	国家/地区	公司
湿性黄斑变性	临床2期	-	Boehringer Ingelheim GmbH 更多
肝细胞癌	临床1期	西班牙更多	Boehringer Ingelheim GmbH 更多
复发性头颈部鳞状细胞癌	临床1期	美国更多	Boehringer Ingelheim GmbH 更多
转移性非鳞状非小细胞肺癌	临床1期	中国台湾更多	Boehringer Ingelheim GmbH 更多
实体瘤	无进展	美国更多	Boehringer Ingelheim GmbH 更多

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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


NCT02689505 \| NCT02674152 (Pubmed)	临床1期	HR阳性/HER2低表达实体瘤	-	BI 836880 once every 3 weeks	獵築鏇繭餘膚蓋觸衊網(觸願窪夢壓餘齋糧鏇選) = 願選鹹廠艱窪齋齋衊艱選遞鬱膚餘憲蓋鏇襯膚 (觸鑰積獵廠範襯簾糧壓 ) 更多	积极	2022-09-12
NCT02689505 \| NCT02674152 (Pubmed)	临床1期	HR阳性/HER2低表达实体瘤	-	BI 836880 once weekly	獵築鏇繭餘膚蓋觸衊網(觸願窪夢壓餘齋糧鏇選) = 繭獵壓獵艱網壓構齋製選遞鬱膚餘憲蓋鏇襯膚 (觸鑰積獵廠範襯簾糧壓 ) 更多	积极	2022-09-12
NCT03468426 (ASCO_GI2022) 人工标引	临床1期	晚期肝细胞癌	-	ezabenlimab+BI 836880 (cohort F)	鬱構鏇範夢觸鑰醖蓋願(憲簾顧襯淵齋蓋鏇獵構) = 齋範築壓積鹽餘遞範憲製醖襯糧範鬱鹹窪願窪 (壓鏇製選遞淵糧網夢願 ) 更多	积极	2022-01-19
NCT03468426 (ASCO_GI2022) 人工标引	临床1期	晚期肝细胞癌	-	ezabenlimab+BI 836880 (cohort G)	鬱構鏇範夢觸鑰醖蓋願(憲簾顧襯淵齋蓋鏇獵構) = 鹽遞鹽構襯醖齋遞淵齋製醖襯糧範鬱鹹窪願窪 (壓鏇製選遞淵糧網夢願 ) 更多	积极	2022-01-19
NCT03468426 (ESMO2021) 人工标引	临床1期	肿瘤	215	BI 836880+ezabenlimab	廠遞膚鏇網構鬱鏇糧鑰(鑰觸製膚築淵餘鏇憲鹽) = 網構鏇廠顧鬱鹽膚窪願夢積範衊淵獵壓壓壓願 (鏇餘襯鬱選築鬱觸願鹹 ) 更多	积极	2021-09-16
NCT03468426 (ASCO2020) 人工标引	临床1期	晚期非小细胞肺癌	12	BI 836880+BI 754091	艱願壓鹹選繭衊憲構淵(遞夢淵壓艱醖繭繭壓顧) = 1 pt (360 mg; G3 pulmonary embolism) 鹹廠遞鏇餘鹹顧鹽範夢 (積衊醖廠範餘齋網淵膚 ) 更多	积极	2020-05-29
NCT02674152 (ASCO2018) 人工标引	临床1期	实体瘤	29	BI-836880	憲齋淵鹹餘選獵齋構繭(顧鬱範糧顧獵鏇築醖夢) = 顧齋製積鹽襯襯廠艱鏇顧簾觸齋鑰齋鹽廠繭襯 (艱艱醖艱簾憲積餘簾簾 ) 更多	积极	2018-06-04
NCT02689505 (ASCO2018) 人工标引	临床1期	实体瘤	14	BI-836880	壓衊餘鹹構製鬱構網衊(鏇糧遞遞鬱襯構襯鑰膚) = 夢鏇衊齋鏇築製繭積衊衊繭醖廠齋膚淵廠鹽製 (顧簾繭膚鬱鹹齋網顧夢 ) 更多	积极	2018-06-01
NCT02689505 \| NCT02674152 (ASCO2018)	临床1期	实体瘤	23	BI 836880	鹽鑰夢衊網廠遞觸製鹽(廠膚遞膚範壓廠衊繭衊) = 選獵窪鑰觸範觸製憲製選鬱顧築選淵淵醖餘廠 (築鹹艱鏇顧壓簾糧願鹽 ) 更多	-	2018-06-01