Phase Ib/II Study to Evaluate Safety and Tolerability of Neoadjuvant Nivolumab and Chemotherapy in Patients With Localized Triple-negative Breast Cancer

Prior to Amendment #7: The hypothesis of this study is that the combination of cabiralizumab and nivolumab with neoadjuvant chemotherapy will decrease tumor associated macrophages (TAMs) and increase tumor infiltrating lymphocytes (TIL) compared to neoadjuvant chemotherapy plus nivolumab in patients with early stage triple-negative breast cancer (TNBC) and improve clinical outcomes.
As of Amendment #7 IRB approved 10/13/2022: The study will no longer enroll to Arm B. Cabiralizumab will no longer be given. The hypothesis of this study is that on-treatment tumor associated macrophages (TAMs) and tumor infiltrating lymphocytes (TILs) will improve (reduced TAMs, increased TILs) following neoadjuvant nivolumab with chemotherapy.

开始日期2020-11-19

申办/合作机构

Washington University School of Medicine

[+1]

NCT03768531

/ Withdrawn临床2期IIT

Safety and Tolerability Study of Combination Nivolumab and Cabiralizumab as Neoadjuvant and Adjuvant Therapy for Resectable Biliary Tract Cancer

The purposed of this research is to study the safety and clinical activity of the combination of nivolumab and cabiralizumab in people with resectable biliary tract cancers (BTC).

开始日期2019-06-14

申办/合作机构

The Sidney Kimmel Comprehensive Cancer Center

[+1]

NCT03927105

/ Completed临床2期IIT

Nivolumab and the Antagonistic CSF-1R Monoclonal Antibody Cabiralizumab (BMS-986227) in Patients With Relapsed/Refractory Peripheral T Cell Lymphoma

A multicenter trial evaluating the combination of nivolumab and the antagonistic CSF-1R monoclonal antibody cabiralizumab (BMS-986227) in patients with relapsed/refractory peripheral T cell lymphoma

开始日期2019-04-25

申办/合作机构

Rogel Cancer Center: University of Michigan

[+1]

100 项与 Cabiralizumab 相关的临床结果

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100 项与 Cabiralizumab 相关的转化医学

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100 项与 Cabiralizumab 相关的专利（医药）

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项与 Cabiralizumab 相关的文献（医药）

2024-09-01·EUROPEAN JOURNAL OF CANCER

Safety of combined ablative radiotherapy and immune checkpoint inhibitors in three phase I trials

Article

作者: Korpics, Mark C ; Pitroda, Sean P ; Chmura, Steven J ; Katipally, Rohan R ; Patel, Jyoti D ; Juloori, Aditya ; Bestvina, Christine M ; Luke, Jason J ; Lynch, Connor

BACKGROUND:

Stereotactic body radiotherapy (SBRT) is safe and effective for treatment of extracranial metastatic disease, but its safety when combined with immune checkpoint inhibitors (ICI) has not yet been comprehensively reported. Here we report adverse events (AEs) associated with combined SBRT and ICI using prospectively-collected data on patients in three trials investigating multi-site SBRT combined with ICI.

METHODS:

Patients were included from three prospective trials of ICI (pembrolizumab; nivolumab/urelumab or nivolumab/cabiralizumab; nivolumab/ipilimumab) with SBRT to 1-4 sites. AEs were recorded prospectively using the CTCAE v4.0. Survival was analyzed using Kaplan-Meier method with a 90-day landmark. Association of patient characteristics with cumulative incidence of AEs was assessed using Fine-Gray regression.

RESULTS:

213 patients were included, with a median follow-up of 10 months. Over the follow-up period, 50 % and 27 % of patients experienced at least one grade ≥ 2 or grade ≥ 3 AE, respectively. Cumulative incidences of grade ≥ 2 and grade ≥ 3 AEs at 6 months were 47 % and 23 %, respectively. Three grade 5 AEs rated "possibly" related to treatment occurred outside the 90-day dose-limiting toxicity window. Landmarked survival analysis of patients with or without grade ≥ 3 AEs showed no significant difference in progression-free or overall survival. Dual-agent ICI was significantly associated with grade ≥ 3 AE.

CONCLUSION:

This analysis features the largest prospectively evaluated cohort of patients treated with combination ablative SBRT and ICI to date and provides context for future trial design. We conclude that multi-site SBRT and ICI can be safely co-administered when SBRT is delivered with prioritization of normal tissue constraints.

2023-10-01·International journal of radiation oncology, biology, physics

Predictors of Hepatotoxicity in Patients with Metastatic Solid Tumors Treated with Immune Checkpoint Inhibition (ICI) and Liver-Directed SBRT.

Article

作者: Lynch, C ; Juloori, A ; Chmura, S J ; Pitroda, S P ; Bestvina, C M ; Korpics, M C ; Katipally, R R

PURPOSE/OBJECTIVE(S):

Liver-metastasis-directed SBRT (LM-SBRT) alone provides durable local control for liver metastases with low rates of toxicity when adhering to established dose constraints. Whether these constraints are sufficient in the context of concurrent ICI is not established. To determine whether LM-SBRT contributes to hepatotoxic adverse events (HAE) in patients receiving ICI, we analyzed potential predictors of HAE in a prospectively evaluated cohort of clinical trial patients treated with both SBRT and ICI.

MATERIALS/METHODS:

Patients with metastatic solid tumors were included from three trials of multi-site SBRT with ICI given concurrently or shortly after SBRT provided they received all study treatments and were monitored for adverse events. ICI agents included pembrolizumab alone or dual agent ICI with nivolumab and either cabiralizumab, urelumab, or ipilimumab. LM-SBRT was delivered to 45 Gy in 3 fr with mean liver dose (MLD) limited to 16 Gy and <700 cc of liver receiving 17.1 Gy. HAE were defined using CTCAE 4.0 as: elevation of AST, ALT, bilirubin or alkaline phosphatase; autoimmune hepatitis; hepatic failure; or cholecystitis. HAE were included if rated at least possibly related to treatment by the trial monitoring committee. Cumulative incidence (CI) of HAE was modeled with death as a competing risk. Competing risks regression was performed using Fine-Gray modeling.

RESULTS:

Two hundred thirteen patients were evaluable. Median follow-up was 10 months. Median age was 61, 90 had liver metastases at treatment, 65 received SBRT to a liver lesion, 15 had underlying liver disease (cirrhosis or hepatic steatosis) and 13 patients had a primary liver cancer. Dual agent ICI was given to 97 patients. Table 1 shows CI at 6 months of grades 1-4 HAE in all patients, LM-SBRT patients and non-liver SBRT patients (NL-SBRT). None experienced grade 5 HAE. There was no significant difference in CI of any grade of HAE between LM-SBRT and NL-SBRT patients. This was also true when comparing LM-SBRT patients to NL-SBRT patients with <0.1 Gy MLD. ICI dose reduction or cessation due to HAE occurred in 4 patients, none of whom received LM-SBRT. On univariate analysis, underlying liver disease and dual agent ICI were significantly associated with grade 2+ HAE while age, LM-SBRT, MLD, primary liver cancer and presence of liver metastases at treatment were not. On multivariate analysis, underlying liver disease and dual agent ICI remained significantly associated with grade 2+ HAE (HR: 6.7, 95% CI 2.3 - 19.1; 4.7, 95% CI 1.7 - 13.0). LM-SBRT and MLD were not significant on MVA.

CONCLUSION:

LM-SBRT did not significantly increase the risk for hepatotoxicity in patients receiving ICI when respecting the above dose constraints. Risk for hepatotoxicity appears to be driven by dual agent ICI and underlying liver disease.

2023-10-01·Hematology/oncology and stem cell therapy

Updates on the Treatment of Tenosynovial Giant Cell Tumor

Review

作者: Chan, Abigail S. ; Singh, Vikas ; Dy, Paul ; Katiyar, Vatsala

Tenosynovial giant cell tumor (TGCT) is a rare inflammatory disorder affecting the joint synovium, bursae, and tendon sheaths that causes non-specific and often insidious joint discomfort. The application of systemic chemotherapy has been limited due to poor and unsustained disease responses. Surgery with or without adjuvant radiation is the primary treatment modality for TGCT. With its locally destructive nature and increased recurrence, multiple surgical interventions become necessary throughout the course of the disease, leading to disfigurement, decreased quality of life, and increased mortality. However, owing to recent evidence demonstrating the overexpression of colony-stimulating factor 1 (CSF-1) in TGCT, selective tyrosine kinase inhibitors targeting CSF-1 receptors are being developed. Pex- idartinib is the first CSF-1 receptor inhibitor approved for the treatment of TGCT. Here, we discuss various available treatment strategies and ongoing investigations and trials targeting diffuse TGCT, which include nilotinib, lacnotuzu- mab, cabiralizumab, vimseltinib, and emactuzumab.

项与 Cabiralizumab 相关的新闻（医药）

2023-02-20

·药明康德

突破癌症治疗耐药性！一文了解这种靶向疗法的最新进展

▎药明康德内容团队编辑随着各式免疫疗法进入临床，甚至成为许多癌症种类的标准疗法，免疫细胞所作用的肿瘤微环境（TME）对于癌症进展与治疗效果的影响也逐渐得到重视。近日《自然》子刊Nature Reviews Caner针对靶向TME内髓系细胞的治疗进展发布了一篇深度综述。药明康德内容团队以其中的肿瘤相关巨噬细胞（TAM）靶向疗法为中心，向读者们介绍其中最新的相关临床进展。若欲阅读综述全文，点击文末“阅读原文/Read more”即可访问原始论文页面。肿瘤微环境与癌症治疗TME指的是肿瘤形成所在的多细胞复杂环境，通常由肿瘤相关成纤维细胞（CAF）、细胞基质、肿瘤微血管与免疫细胞等所构成。TME中免疫细胞包含了淋巴细胞（如T细胞、B细胞）与不同种类的髓系细胞（myeloid cells）。巨噬细胞是髓系细胞的一种，在TME中存在具正常活化的巨噬细胞，这类细胞能够毒杀癌细胞、呈递肿瘤抗原、致敏T细胞（T cell priming）、产生吞噬作用（phagocytosis）与刺激性细胞因子等抗肿瘤作用，在人体免疫系统对抗癌细胞中扮演关键角色。然而在TME中亦存在具免疫抑制性的TAM，这类细胞会分泌抑制性因子、改变TME、促进癌细胞分化与抑制T细胞毒杀功能，是肿瘤对化疗与免疫检查点抑制剂产生耐药性的重要原因之一。研究人员通过对肿瘤组织进行包含CD68、CD86、CD163或CD206等生物标志物的免疫染色，可以识别TAM。研究发现，肿瘤内TAM高频率的出现与许多类型癌症患者的不良预后相关。这些TAM是受其所表达的集落刺激因子-1受体（CSF1R）与趋化因子受体2（CCR2）的调节而进入肿瘤组织。临床前研究发现，当以抗体或小分子阻断CSF1R与其配体的结合时，可以降低不同种类实体瘤组织内TAM的数量并产生抗肿瘤作用。另一方面，当抑制CCR2表达时会导致小鼠结直肠癌肿瘤缩小。这些临床前研究为开发靶向TAM疗法打下了基础。▲肿瘤微环境示意图（图片来源：参考资料[2]）靶向巨噬细胞的治疗策略降低肿瘤组织中TAM的数量或改变其特性，已成为临床上改善患者对化疗与免疫疗法耐药性的重要方向。根据策略的不同，大致上可以分成三种类型：抑制肿瘤募集巨噬细胞、重新编程巨噬细胞、恢复巨噬细胞抗肿瘤能力。抑制肿瘤募集巨噬细胞临床上主要是通过药物阻断CSF1R与CCR2受体的活化以阻止巨噬细胞进入肿瘤组织中。至今已有超过30个临床1、2期试验检视靶向这两种受体通路的在研小分子或抗体。进入临床试验内的靶向CSF1R抗体包含emactuzumab、AMG 820、LY3022855、cabiralizumab，而靶向其配体CSF1的抗体则有lacnotuzumab。另外ARRY-382、BLZ945、pexidartinib、edicotinib则为进入临床的CSF1R小分子抑制剂。第一三共（Daiichi Sankyo）所开发的pexidartinib（商品名：Turalio）在2019年获FDA批准上市，用于治疗症状性腱鞘巨细胞瘤（TGCT）成人患者。TGCT是一种具备局部侵袭性的罕见非恶性肿瘤，会导致关节或肢体出现肿胀、疼痛、僵硬，以及活动范围下降。目前pexidartinib与化疗或免疫检查点抑制剂组合联用，正于多项临床1、2期试验中受检视，治疗包含结直肠癌、乳腺癌、胰腺癌等实体瘤。此外，Five Prime与百时美施贵宝（BMS）联合开发的cabiralizumab与PD-1抑制剂nivolumab组合，治疗肝癌、胰腺癌等实体瘤的多项临床2期试验也正在进行中。靶向CCR2的疗法则不如抑制CSF1R广为人所探索。临床试验显示，CCR2抑制剂PF-04136309与化疗方案FOLFIRINOX联用治疗胰腺癌的效力较化疗方案单独使用高，但差异并不具统计意义。目前BMS所开发CCR2/5抑制剂BMS-813160的组合方案正在多项临床1、2期试验中受检视，用于治疗非小细胞肺癌、肝癌与胰腺癌。▲不同靶向巨噬细胞抗癌机制（图片来源：参考资料[1]）重新编程巨噬细胞小分子抑制剂能调节TAM的分化与功能，进而降低其免疫抑制特性，甚至可能恢复TAM的抗肿瘤能力。例如由Infinity Pharmaceuticals所开发的潜在“first-in-class” PI3K-γ激酶抑制剂eganelisib可以通过将TAM重新编程，将其从免疫抑制转变为免疫激活，从而增强细胞的抗肿瘤活性。一项eganelisib与PD-L1抗体atezolizumab和白蛋白紫杉醇联用，一线治疗三阴性乳腺癌患者的2期临床试验结果显示，在44名可评估患者中，92.8%携带PD-L1阳性肿瘤的患者观察到肿瘤缩小，85.2%携带PD-L1阴性肿瘤的患者观察到肿瘤缩小。目前eganelisib作为单药或与nivolumab联用治疗头颈癌与膀胱癌的临床2期试验正在进行中。此外，通过调节控制巨噬细胞分化的IL-6-JAK-STAT通路亦可能改变TAM的免疫抑制特性。靶向转录因子STAT3的反义寡核苷酸疗法AZD9150曾在具免疫检查点抑制剂耐药性的癌症患者中受检视，其在头颈癌的临床疗效不如预期，而在肺癌患者身上的数据则尚未公布。恢复巨噬细胞抗肿瘤能力CD47是细胞表面表达的“别吃我”信号，通过与巨噬细胞表面的SIRPα受体结合，防止正常细胞被巨噬细胞吞噬。然而在多种癌症类型中，肿瘤细胞也会通过表达CD47防止它们被巨噬细胞吞噬，因此靶向SIRPα/CD47免疫检查点信号通路可促进巨噬细胞靶向消灭癌细胞。吉利德潜在“first-in-class”CD47抑制剂magrolimab便属于此类疗法，一项1b期临床试验的结果显示，在33名可评估疗效的患者中，magrolimab和阿扎胞苷构成的组合疗法达到91%的客观缓解率，42%的患者达到了完全缓解。目前magrolimab组合疗法的多项临床试验正在进行中，包含三项针对血液肿瘤、正在进行的3期临床试验。此外，BMS所开发的CC-95251是一款靶向SIRPα的单克隆抗体，它在治疗非霍奇金淋巴瘤的临床试验中已经表现出积极的活性和安全性，达到41%的客观缓解率。图片来源：123RF除了上述的几种疗法外，靶向CD39、CD73这两种胞外核苷酸水解酶亦是潜在激活巨噬细胞抗肿瘤功能的方式。胞外核苷酸水解酶可催化细胞外ATP（eATP）水解成胞外腺苷，胞外腺苷会抑制免疫反应。CD39、CD73在多种实体肿瘤中高度表达。研究发现，胞外核苷酸水解酶的靶向疗法能够激活巨噬细胞中的炎症小体，增加其抗肿瘤能力。在去年AACR年会当中，Trishula公司和艾伯维（AbbVie）合作开发的抗CD39抗体TTX-030，在晚期胃癌患者中作为一线疗法展现积极数据。在38例可评估疗效的患者中，23名患者获得部分缓解以上的应答，其中包括两名完全缓解，12例患者为疾病稳定，客观缓解率为61%。改善临床巨噬细胞靶向疗法由于癌症种类的不同，以及同一种癌症中不同个体肿瘤间的差异，巨噬细胞靶向疗法在不同癌症患者身上显示出不同的效力。例如，在针对脑瘤的一项研究发现，肿瘤内不同亚型的巨噬细胞对不同疗法的应答性相异。这显示在进行相关临床试验的时候，应该考虑根据肿瘤类型对病患进行分类以提高试验的成功率。尤其随着癌症不同期别的进展，巨噬细胞在肿瘤内的数量与特性亦会随之改变。过往研究显示，在人类与小鼠肺腺癌肿瘤中，TAM在疾病早期阶段会促进免疫逃逸、肿瘤生长与转移。然而随着肿瘤进展，TAM会被限制在肿瘤外周，而肿瘤内则由源自造血系统的巨噬细胞所取代，这项发现显示TAM靶向疗法可能对早期肺癌患者更具效果。图片来源：123RF除了通过肿瘤期别与潜在的生物标志物对患者进行分类外，另一项改善巨噬细胞靶向疗法的方向则是优化不同药物组合、给药方式与时间点。目前多数试验是通过慢性、持续性的给药方式，然而慢性CSF1R抑制剂的给予常常因为病患肝毒性的产生而被迫停止。此外，长期持续性的给药也有可能削弱身体免疫系统抵抗肿瘤的能力。因此研究人员可能需要通过不同药物组合以平衡治疗的效果与毒性，并尝试间歇性给药或不同时间点给药等各种安排以达到最佳的治疗效果。限于篇幅，本文并未对综述全文一一介绍。巨噬细胞靶向疗法是一项新兴的免疫疗法，科学家们仍在许多未知变数当中探索，但如同过往许多医学进展一般，这是医学突破前所必须经历的一个过程。让我们期待科学家能够早日获得积极试验结果，改善广大癌症患者的生活。大家都在看▲欲了解更多前沿技术在生物医药产业中的应用，请长按扫描上方二维码，即可访问“药明直播间”，观看相关话题的直播讨论与精彩回放‍‍参考资料：[1] Barry, Simon T et al. “Therapeutic targeting of tumour myeloid cells.” Nature reviews. Cancer, 10.1038/s41568-022-00546-2. 6 Feb. 2023, doi:10.1038/s41568-022-00546-2[2] Bejarano, Leire et al. “Therapeutic Targeting of the Tumor Microenvironment.” Cancer discovery vol. 11,4 (2021): 933-959. doi:10.1158/2159-8290.CD-20-1808免责声明：药明康德内容团队专注介绍全球生物医药健康研究进展。本文仅作信息交流之目的，文中观点不代表药明康德立场，亦不代表药明康德支持或反对文中观点。本文也不是治疗方案推荐。如需获得治疗方案指导，请前往正规医院就诊。版权说明：本文来自药明康德内容团队，欢迎个人转发至朋友圈，谢绝媒体或机构未经授权以任何形式转载至其他平台。转载授权请在「药明康德」微信公众号回复“转载”，获取转载须知。分享，点赞，在看，聚焦全球生物医药健康创新

免疫疗法临床2期

2023-01-02

·PRNewswire

Propulsion of Pancreatic Cancer Pipeline as Novel and Extensive 170+ Therapies Likely to Enter in the Treatment Domain | DelveInsight

The prevalence of pancreatic cancer has been rising since the past few years, which prompts the growing demand for treatment options. The increasing prevalence of cancer, the robust pipeline, and the growing research and development activities to develop novel therapies to treat Pancreatic Cancer drive the market. The companies developing the potential therapies in the last stage of development include FibroGen, Eli Lilly and Company, CARsgen Therapeutics, and several others. LAS VEGAS, Jan. 2, 2023 /PRNewswire/ -- DelveInsight's ' Pancreatic Cancer Pipeline Insight – 2022 ' report provides comprehensive global coverage of available, marketed, and pipeline pancreatic cancer therapies in various stages of clinical development, major pharmaceutical companies are working to advance the pipeline space and future growth potential of the pancreatic cancer pipeline domain. Key Takeaways from the Pancreatic Cancer Pipeline Report DelveInsight's pancreatic cancer pipeline report depicts a robust space with 150+ active players working to develop 170+ pipeline therapies for pancreatic cancer treatment. Key pancreatic cancer companies such as FibroGen, Innovent Biologics, CARsgen Therapeutics, Ascentage Pharma, NGM Biopharmaceuticals, TME Pharma AG, Lee's Pharmaceutical Limited, ImmunityBio, Inc., Rgene Corporation, CSPC ZhongQi Pharmaceutical Technology Co., Ltd., CanBas Co. Ltd., Jiangsu HengRui Medicine Co., Ltd., Bristol-Myers Squibb, SynerGene Therapeutics, Inc., AbbVie, Silenseed Ltd, Galera Therapeutics, Inc., Helix BioPharma, Golden Biotechnology Corporation, Eli Lilly and Company, Innovent Biologics (Suzhou) Co. Ltd., Panbela Therapeutics, Inc., GlaxoSmithKline, Chia Tai Tianqing Pharmaceutical Group, Roche, Prestige Biopharma Limited, Everfront Biotech Co., Ltd., XBiotech, Inc., Incyte Corporation, Ability Pharmaceuticals SL, Lokon Pharma, HCW Biologics, Amplia Therapeutics Limited, BioLineRx, Ltd., Taiho Pharmaceutical, Sanofi, Scandion Oncology, Nelum, Celldex Therapeutics, Merus N.V., Seagen Inc., GC Cell Corporation, MetiMedi Pharmaceuticals, Lumicell, Nuvation Bio Inc., ENB Therapeutics, BioNTech SE, Bayer, Genentech, Inc., Rise Biopharmaceuticals, Inc., Prestige Biopharma Limited, iOnctura, Shanghai Unicar-Therapy Bio-medicine Technology, Shanghai Hengrui Pharmaceutical Co., Ltd., Hangzhou Neoantigen Therapeutics Co., Ltd., EUSA Pharma, Inc.,Agenus Inc., Arcus Biosciences, Inc.Amgen, Biomea Fusion, and others are evaluating pancreatic cancer drugs to improve the treatment landscape. Promising pancreatic cancer pipeline therapies in various stages of development include Pamrevlumab, Niraparib, CT041, APG-1387, BNT141, ENB003, NUV-868, MCLA-128, LUM015, tisotumab vedotin, OMT-111, tusamitamab ravtansine, SCO-101, NGM120, CDX-301, NLM-001, TAS 102, Olaptesed pegol, BL-8040, Gimatecan, AMP945, N-803, HCW9218, BLEX 404, delolimogene mupadenorepvec, Mitoxantrone Hydrochloride Liposome injection, ABTL0812, CBP501, Pemigatinib, SHR-1701, Fluzoparib, XB2001, Cabiralizumab, EF-009, SGT-53, ABBV-927, PBP1510, Vemurafenib, siG12D-LODER, Penpulimab, GC4711, GSK2256098, L-DOS47, SBP-101, Antroquinonol, LY3214996, Sintilimab, RP72, PBP1510, IOA-289, U87, MVT-5873, SHR-A1904, iNeo-Vac-P01, iNeo-Vac-P01, TQB2858, Siltuximab, AGEN1423, AB680, AMG 199, BMF-219, and others. In December 2022, Targovax ASA announced that it has entered into a collaboration agreement with The University of Kansas Cancer Center (KU Cancer Center) and Agenus Inc. to run a clinical trial testing mutant RAS vaccine TG01 in combination with PD-1 CPI balstilimab in pancreatic cancer following surgery and standard-of-care (SoC) chemotherapy. In December 2022, Bluestar Genomics, Inc. announced the initiation of the New Onset Diabetes Management for Earlier Detection (NODMED) trial, one of the largest clinical studies in pancreatic cancer to date. The trial will use Bluestar Genomics' proprietary epigenomic methods for the detection of the disease. In December 2022, iOnctura BV, a clinical-stage biotech developing novel cancer therapies, had been granted €17.5 million ($18.6 million) funding from the European Investment Council's (EIC) accelerator program to develop IOA-289 for pancreatic cancer.The EIC's funding consists of a grant of €2.5 million ($2.7 million) and €15 million ($16 million) of equity investment. In December 2022, In the Phase I/II CodeBreaK 100 trial, the KRAS G12C inhibitor sotorasib achieved meaningful anticancer activity with an acceptable safety profile in heavily pretreated patients with KRAS G12C-mutated metastatic pancreatic cancer, according to researchers at The University of Texas MD Anderson Cancer Center. The results of the trial, published in the The New England Journal of Medicine, indicate an objective response rate of 21.1% and a median time-to-response of 1.5 months, with 84% of patients experiencing disease control. Median progression-free survival was 4 months, and overall survival was 6.9 months. In December 2022, Oncolytics Biotech® Inc. announced that the U.S. Food and Drug Administration (FDA) has granted Fast Track designation to pelareorep in combination with Roche's anti-PD-L1 checkpoint inhibitor atezolizumab, and the chemotherapeutic agents gemcitabine and nab-paclitaxel, for the treatment of advanced/metastatic pancreatic ductal adenocarcinoma (PDAC). This represents pelareorep's second FDA Fast Track designation. In December 2022, RemeGen Co., Ltd. announced that its latest antibody-drug conjugate (ADC), RC118 for injection, has been granted two orphan drug designations (ODD) by the United States Food and Drug Administration (FDA) for gastric cancer (including gastroesophageal junction cancer) and pancreatic cancer. This marks the Company's fourth, having previously been granted ODD twice for Disitamab Vedotin (RC48) and Telitacicept (RC18) earlier this year. In December 2022, Panbela Therapeutics, Inc. announced that the European Medicines Agency (EMA) Committee for Orphan Medicinal Products issued a positive opinion on Panbela's application for orphan designation of ivospemin ( SBP-101) in combination with gemcitabine and nab-Paclitaxel in patients with metastatic pancreatic ductal adenocarcinoma (PDA). In September 2022, Qualigen Therapeutics, Inc. announced the presentation of two posters on QN-302 at the AACR 8th Special Conference on Pancreatic Cancer. The data presented include information on the compound's safety, tolerability, and efficacy in a pancreatic cancer model. The poster included preclinical toxicology data that showed QN-302 does not produce adverse toxicological reactions in mouse models at therapeutic doses. In in vitro tests, QN-302 inhibits acetylcholinesterase (AChE) by 53% and muscarinic receptor (M2) by 70% at 1 µM. Request a sample and discover the recent advances in pancreatic cancer drugs @ Pancreatic Cancer Pipeline Report The pancreatic cancer pipeline report provides detailed profiles of pipeline assets, a comparative analysis of clinical and non-clinical stage pancreatic cancer drugs, inactive and dormant assets, a comprehensive assessment of driving and restraining factors, and an assessment of opportunities and risks in the pancreatic cancer clinical trial landscape. Pancreatic Cancer Overview Pancreatic cancer develops in the pancreas tissues, an abdomen organ located behind the stomach's bottom portion. The pancreas secretes hormones that help control blood sugar and enzymes that aid digestion. Pancreatic cancer is a condition in which malignant (cancer) cells develop in pancreatic tissues. The pancreas can develop tumors in various ways, including malignant and noncancerous tumors. However, the precise causes of pancreatic cancer are unknown. Individuals diagnosed with pancreatic cancer before the tumor develops or spreads have an average life expectancy of pancreatic cancer of 3 to 3.5 years. Pancreatic cancer symptoms may include jaundice, dark urine, weight loss, loss of appetite, fatigue, and others. A pancreatic cancer diagnosis is difficult because symptoms are frequently confused with those of other disorders, such as irritable bowel syndrome. The extent of the cancer determines the treatment of pancreatic cancer options. Pancreatic cancer treatment options may include surgery, chemotherapy, radiation therapy, targeted therapy, or a combination of these. Learn more about the diseases and pancreatic cancer diet @ Pancreatic Cancer Tests A snapshot of the Pancreatic Cancer Pipeline Drugs mentioned in the report: Learn more about the emerging pancreatic cancer treatment options @ Pancreatic Cancer Clinical Trials Pancreatic Cancer Therapeutics Assessment The pancreatic cancer pipeline report proffers an integral view of pancreatic cancer emerging novel therapies segmented by stage, product type, molecule type, mechanism of action, and route of administration. Scope of the Pancreatic Cancer Pipeline Report Coverage: Global Therapeutic Assessment By Product Type: Mono, Combination, Mono/Combination Therapeutic Assessment By Clinical Stages: Discovery, Pre-clinical, Phase I, Phase II, Phase III Therapeutics Assessment By Route of Administration: Inhalation, Intranasal, Intravenous, Oral, Parenteral, Subcutaneous Therapeutics Assessment By Molecule Type: Antibody, Antisense oligonucleotides, Immunotherapy, Monoclonal antibody, Peptides, Protein, Recombinant protein, Small molecule, Stem Cell, Vaccine Therapeutics Assessment By Mechanism of Action: Connective tissue growth factor inhibitors, Poly(ADP-ribose) polymerase 1 inhibitors, Poly(ADP-ribose) polymerase 2 inhibitors, Immunologic cytotoxicity, T lymphocyte replacements, Growth differentiation factor 15 inhibitors, Endothelin B receptor antagonists, Image enhancers Key Pancreatic Cancer Companies: FibroGen, Innovent Biologics, CARsgen Therapeutics, Ascentage Pharma, NGM Biopharmaceuticals, TME Pharma AG, Lee's Pharmaceutical Limited, ImmunityBio, Inc., Rgene Corporation, CSPC ZhongQi Pharmaceutical Technology Co., Ltd., CanBas Co. Ltd., Jiangsu HengRui Medicine Co., Ltd., Bristol-Myers Squibb, SynerGene Therapeutics, Inc., AbbVie, Silenseed Ltd, Galera Therapeutics, Inc., Helix BioPharma, Golden Biotechnology Corporation, Eli Lilly and Company, Innovent Biologics (Suzhou) Co. Ltd., Panbela Therapeutics, Inc., GlaxoSmithKline, Chia Tai Tianqing Pharmaceutical Group, Roche, Prestige Biopharma Limited, Everfront Biotech Co., Ltd., XBiotech, Inc., Incyte Corporation, Ability Pharmaceuticals SL, Lokon Pharma, HCW Biologics, Amplia Therapeutics Limited, BioLineRx, Ltd., Taiho Pharmaceutical, Sanofi, Scandion Oncology, Nelum, Celldex Therapeutics, Merus N.V., Seagen Inc., GC Cell Corporation, MetiMedi Pharmaceuticals, Lumicell, Nuvation Bio Inc., ENB Therapeutics, BioNTech SE, Bayer, Genentech, Inc., Rise Biopharmaceuticals, Inc., Prestige Biopharma Limited, iOnctura, Shanghai Unicar-Therapy Bio-medicine Technology, Shanghai Hengrui Pharmaceutical Co., Ltd., Hangzhou Neoantigen Therapeutics Co., Ltd., EUSA Pharma, Inc.,Agenus Inc., Arcus Biosciences, Inc., Amgen, Biomea Fusion, and others. Key Pancreatic Cancer Pipeline Therapies: Pamrevlumab, Niraparib, CT041, APG-1387, BNT141, ENB003, NUV-868, MCLA-128, LUM015, tisotumab vedotin, OMT-111, tusamitamab ravtansine, SCO-101, NGM120, CDX-301, NLM-001, TAS 102, Olaptesed pegol, BL-8040, Gimatecan, AMP945, N-803, HCW9218, BLEX 404, delolimogene mupadenorepvec, Mitoxantrone Hydrochloride Liposome injection, ABTL0812, CBP501, Pemigatinib, SHR-1701, Fluzoparib, XB2001, Cabiralizumab, EF-009, SGT-53, ABBV-927, PBP1510, Vemurafenib, siG12D-LODER, Penpulimab, GC4711, GSK2256098, L-DOS47, SBP-101, Antroquinonol, LY3214996, Sintilimab, RP72,PBP1510, IOA-289, U87, MVT-5873, SHR-A1904, iNeo-Vac-P01, iNeo-Vac-P01, TQB2858, Siltuximab, AGEN1423, AB680, AMG 199, BMF-219, and others. Dive deep into rich insights for pancreatic cancer research; visit @ New Treatment for Pancreatic Cancer Table of Contents For further information on pancreatic cancer prevention, reach out @ Pancreatic Cancer Drug Treatment Related Reports Pancreatic Cancer Epidemiology Pancreatic Cancer Epidemiology Forecast – 2032 report delivers an in-depth understanding of the disease, historical, and forecasted pancreatic cancer epidemiology in the 7MM. Pancreatic Cancer Market Pancreatic Cancer Market Insight, Epidemiology, and Market Forecast – 2032 report delivers an in-depth understanding of the market trends, market drivers, market barriers, and key pancreatic cancer companies, including FibroGen, NeoImmuneTech, NOXXON Pharma, Silenseed Ltd., Amgen, NGM Biopharmaceuticals, among others. Advanced Pancreatic Cancer Market Advanced Pancreatic Cancer Market Insight, Epidemiology, and Market Forecast – 2032 report delivers an in-depth understanding of the market trends, market drivers, market barriers, and key advanced pancreatic cancer companies, including AstraZeneca, Merck Sharp & Dohme LLC, Bayer, Roche, among others. Advanced Pancreatic Cancer Pipeline Advanced Pancreatic Cancer Pipeline Insight – 2022 report provides comprehensive insights about the pipeline landscape, pipeline drug profiles, including clinical and non-clinical stage products, and the key advanced pancreatic cancer companies, including FibroGen, NeoImmuneTech, NOXXON Pharma, Silenseed Ltd., Amgen, NGM Biopharmaceuticals, among others. Metastatic Pancreatic Cancer Market Metastatic Pancreatic Cancer Market Insight, Epidemiology, and Market Forecast – 2032 report delivers an in-depth understanding of the market trends, market drivers, market barriers, and key metastatic pancreatic cancer companies, including Takeda Oncology, Salspera, Eli Lilly and Company, among others. Metastatic Pancreatic Cancer Pipeline Metastatic Pancreatic Cancer Pipeline Insight – 2022 report provides comprehensive insights about the pipeline landscape, pipeline drug profiles, including clinical and non-clinical stage products, and the key metastatic pancreatic cancer companies, including Takeda Oncology, Salspera, Eli Lilly and Company, among others. Other Trending Oncology Reports Follicular lymphoma | Indolent lymphoma | Severe Toxicities In Lymphoma | Marginal Zone Lymphoma | Vulvar Squamous Cell Carcinoma | Cholangiocarcinoma | Metastatic Cutaneous Squamous cell Carcinoma | Nasopharyngeal Carcinoma | Ductal Carcinoma in Situ | Oncolytic Virus Cancer Therapy | Cancer Cachexia | Intratumoral Cancer Therapies | Brain Cancer Related Healthcare Blogs Upcoming Oncology Drugs Oncology Market Outlook Future of Oncology Market Related Cases Studies Competitive Intelligence Market Assessment Product Assessment Epidemiology Assessment Related Healthcare Services Healthcare Business Consulting Healthcare Competitive Intelligence Services Healthcare Asset Prioritization Services About DelveInsight DelveInsight is a leading Business Consultant and Market Research firm focused exclusively on life sciences. Connect with us at LinkedIn Contact Us Shruti Thakur [email protected] +1(919)321-6187 Logo: SOURCE DelveInsight Business Research, LLP

快速通道孤儿药临床结果免疫疗法

2022-07-14

·CPhI制药在线

新药 | 和誉医药1类新药ABSK021上市加速，CSF-1R拮抗剂前途可期

点击关注，星标CPhI制药在线日前，CDE官网显示，上海和誉生物医药科技有限公司1类新药「ABSK021胶囊」拟纳入突破性治疗品种，用于治疗不可手术的腱鞘巨细胞瘤。腱鞘巨细胞瘤（TGCT）是一种罕见的良性软组织肿瘤，主要累及滑膜关节、粘液囊和腱鞘，造成受累关节和肢体的肿胀、疼痛、僵直和活动不便。据估计，腱鞘巨细胞瘤的发病率为每年百万分之十一至五十。手术是TGCT的标准疗法，但对于复发、难治或弥漫性腱鞘巨细胞瘤患者，手术不但难于清除肿瘤，而且可能导致严重关节损伤和功能丧失。2019年FDA批准全球首款TGCT新药，即第一三共的Turalio (pexidartinib)。Turalio 是一款口服CSF-1R小分子抑制剂，被批准用于治疗身体机能严重受限且无法通过手术改善病情的症状性TGCT成人患者。 ABSK021是和誉医药独立自主研发的一款全新的口服、高选择性、高活性CSF-1R小分子抑制剂。初步临床数据表明，ABSK021具有良好的耐受性、药代动力学特性及对靶点的有效抑制。此次纳入突破性治疗品种，将加速ABSK021在国内的上市进程。关于CSF-1R拮抗剂CSF-1R，即抗巨噬细胞集落刺激因子1受体，属于跨膜受体酪氨酸激酶的一种，其功能与巨噬细胞增殖、分化的调控密切相关。研究发现CSF-1R在多种癌症和肿瘤相关巨噬细胞（TAM）中发挥重要作用，可导致肿瘤内微环境的改变并产生免疫抑制效应。阻断CSF-1R信号通路可调节和改变肿瘤微环境，解除肿瘤免疫抑制，并能与免疫检查点抑制剂等多种抗癌疗法产生协同作用，达到良好的抑瘤功能。多项临床研究证实，CSF-1R拮抗剂可用于治疗腱鞘巨细胞瘤（TGCT），也可与肿瘤免疫疗法及其它药物联用治疗多种恶性肿瘤。除了上述提及的ABSK021和Turalio，目前全球还有几款在研CSF-1R拮抗剂，详见下表。这些在研CSF-1R拮抗剂药物类型包括小分子化药和单抗，适应症涵盖肿瘤、神经系统疾病和特发性肺纤维化。其中axatilimab进展相对较快，曾被FDA授予治疗慢性移植物抗宿主病（cGVHD）和特发性肺纤维化（IPF）的孤儿药资格，已公布的1期临床试验结果显示：axatilimab在对多种治疗药物无效的cGVHD患者中有良好的耐受性和高应答率。我国宝船生物、阿诺医药等企业积极布局CSF-1R拮抗剂药物市场，其中阿诺医药研发的AN9015是一款CSF-1R和c-kit双重抑制剂，在小鼠肿瘤模型中更好地逆转免疫抑制性的肿瘤微环境，与临床阶段的主要竞品化合物存在明显的差异，显示出巨大的免疫治疗潜力。然而，CSF-1R拮抗剂的开发并不顺利。Emactuzumab因联合PD-L1单抗Tecentriq治疗实体瘤的临床试验结果不如预期曾一度遭到搁置。Cabiralizumab联合PD-1单抗Opdivo治疗胰腺癌的2期临床也惨遭失败。不过，企业并没有放弃CSF-1R拮抗剂药物开发，近几年围绕该领域达成了数项合作：（1）2020年8月，罗氏与英国Celleron Therapeutics 签署一项合作，授予后者开发、生产和商业化Emactuzumab的全球独家权益。而Celleron Therapeutics 接手Emactuzumab是看中了其治疗弥漫性TGCT的潜力，罗氏先前进行的研究显示，86%（24人）接受该药治疗的TGCT患者产生应答，68%的患者在开始治疗后6周内出现部分反应；（2）2021年2月，福贝生物与Elixiron Immunotherapeutics达成授权合作，共同推进CSF-1R拮抗剂EI-1071在神经系统疾病等领域的开发、生产和商业化工作；（3）2021年7月，曙方医药与和誉医药达成独家授权协议，在大中华地区合作开发创新药ABSK021针对神经系统罕见病领域适应证的应用；（4）2021年9月，Syndax Pharmaceuticals和因赛特（Incyte）达成一项全球合作与独占许可协议，共同开发和商业化axatilimab，用于治疗慢性移植物抗宿主病（cGVHD）和其他纤维化疾病。 -END-【企业推荐】速来投稿参与金笔奖征文，稿费丰厚来源：CPhI制药在线声明：本文仅代表作者观点，并不代表制药在线立场。本网站内容仅出于传递更多信息之目的。如需转载，请务必注明文章来源和作者。投稿邮箱：Kelly.Xiao@imsinoexpo.com▼更多制药资讯，请关注CPhI制药在线▼点击阅读原文，进入智药研习社~

孤儿药创新药抗体小分子药物免疫疗法合作

100 项与 Cabiralizumab 相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
-	-	-	DB15082

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
三阴性乳腺癌	临床2期	美国	Bristol Myers Squibb Co.	2020-11-19
胆道癌	临床2期	-	Bristol Myers Squibb Co.	2019-06-14
外周T细胞淋巴瘤	临床2期	美国	Bristol Myers Squibb Co.	2019-04-25
胰腺癌	临床2期	美国	Bristol Myers Squibb Co.	2017-12-18
胰腺癌	临床2期	日本	Bristol Myers Squibb Co.	2017-12-18
胰腺癌	临床2期	加拿大	Bristol Myers Squibb Co.	2017-12-18
胰腺癌	临床2期	丹麦	Bristol Myers Squibb Co.	2017-12-18
胰腺癌	临床2期	德国	Bristol Myers Squibb Co.	2017-12-18
胰腺癌	临床2期	意大利	Bristol Myers Squibb Co.	2017-12-18
胰腺癌	临床2期	韩国	Bristol Myers Squibb Co.	2017-12-18

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临床结果

适应症

分期

评价

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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


NCT03336216 (CTgov)	临床2期	胰腺癌	205	nab-paclitaxel+gemcitabine+Leucovorin+Irinotecan+5-Fluorouracil (Arm A: Investigator Choice)	願鹽積糧淵艱構醖壓積(遞鹹願壓製鹹衊襯淵鹽) = 窪鹹憲願繭衊遞繭膚顧獵簾蓋願壓選憲繭壓製 (糧製製淵淵淵淵窪顧網, 遞積積構遞齋衊遞鏇壓 ~ 蓋積窪蓋窪遞蓋蓋蓋醖) 更多	-	2024-07-23
				Cabiralizumab+Nivolumab (Arm B: Cabiralizumab + Nivolumab)	願鹽積糧淵艱構醖壓積(遞鹹願壓製鹹衊襯淵鹽) = 艱糧鬱蓋餘築繭獵襯觸獵簾蓋願壓選憲繭壓製 (糧製製淵淵淵淵窪顧網, 鏇襯膚網糧衊夢衊選憲 ~ 顧蓋廠顧襯蓋淵蓋衊積) 更多
NCT04331067 (CTgov)	临床1/2期	三阴性乳腺癌	15	Tumor biopsy+Cabiralizumab+Nivolumab+Carboplatin+Paclitaxel (Arm B: Neoadjuvant Chemo + Nivolumab + Cabiralizumab)	築廠夢襯鑰襯鹽鏇廠齋(鏇願廠餘壓糧糧鑰簾夢) = 繭網鏇憲醖鑰積簾窪艱衊夢窪範艱簾夢鬱願顧 (鬱憲顧製艱餘衊鑰鑰範, 遞築憲繭築顧艱簾鏇積 ~ 糧獵夢鏇繭醖齋醖範襯) 更多	-	2024-05-16
				Tumor biopsy+Nivolumab+Carboplatin+Paclitaxel (Arm A: Neoadjuvant Chemo + Nivolumab)	選窪鹽壓鏇範蓋獵範壓(積築齋築選簾廠鹹齋築) = 選膚顧鑰築鑰遞壓憲醖醖鏇鏇糧網網繭齋鏇製 (網蓋積蓋廠積憲憲鏇網, 襯襯鬱構夢鏇膚鹽窪鏇 ~ 獵顧廠鹽鏇餘積鑰醖網) 更多
NCT03599362 (CTgov)	临床2期	不能切除性胰腺癌	7	Stereotactic Body Radiotherapy (SBRT)+Cabiralizumab+Nivolumab	願願淵觸範願淵遞鬱襯(壓鏇範鹽觸積網壓艱顧) = 窪膚製繭積壓獵憲衊築鑰鏇簾廠廠顧鬱簾齋憲 (範鏇醖製鹹膚齋獵範鏇, 醖夢淵願積夢積襯簾艱 ~ 遞繭淵簾築壓遞構憲餘) 更多	-	2021-10-19
NCT03927105 (CTgov)	临床2期	外周T细胞淋巴瘤	4	cabiralizumab+Nivolumab	鏇簾艱糧獵醖簾鹽窪淵(觸願獵顧壓選淵繭餘鑰) = 積壓蓋願鬱膚糧選襯憲蓋膚觸繭願簾鹽醖遞遞 (鏇壓築鏇襯襯壓鹽齋衊, 衊鬱壓構憲艱憲淵衊選 ~ 膚壓鹹積憲網衊齋憲鹽) 更多	-	2021-09-10
NCT03502330 (Pubmed \| Clin Cancer Res) 人工标引	临床1期	黑色素瘤 \| 非小细胞肺癌 \| 肾肿瘤	26	Sotigalimab+Cabiralizumab+Nivolumab	願蓋夢鹽蓋醖積選選選(簾網壓遞獵網艱鹹簾餘) = asymptomatic elevations of lactate dehydrogenase (n = 26), creatine kinase (n = 25), aspartate aminotransferase (n = 25), and alanine aminotransferase (n = 19); periorbital edema (n = 17); and fatigue (n = 13) 夢醖餘鏇窪製鏇顧遞觸 (膚襯憲鏇齋願獵範蓋顧 ) 更多	积极	2021-09-01
NCT02471716 (FPA008-002, CTgov)	临床1/2期	色素沉着的绒毛结节性滑膜炎	66	FPA008 (Phase 1 FPA008 Dose Escalation 1mg/kg)	艱鏇蓋襯範觸鏇齋範淵(膚築願糧選遞顧鬱構積) = 窪願艱窪淵構醖憲餘憲糧廠艱網積糧夢餘襯壓 (範選構糧窪蓋衊膚鏇壓, 憲積願蓋餘齋網範膚醖 ~ 憲鑰襯醖顧蓋繭範遞衊) 更多	-	2021-08-31
				FPA008 (Phase 1 FPA008 Dose Escalation 2mg/kg)	艱鏇蓋襯範觸鏇齋範淵(膚築願糧選遞顧鬱構積) = 顧觸衊醖襯鹹廠衊糧鹽糧廠艱網積糧夢餘襯壓 (範選構糧窪蓋衊膚鏇壓, 餘選淵製膚蓋選製餘鏇 ~ 範窪鏇淵醖糧鹽憲鹹壓) 更多
NCT03431948 (Pubmed \| Clin Cancer Res) 人工标引	临床1期	HR阳性/HER2低表达实体瘤	60	SBRT+Nivolumab+Urelumab or Cabiralizumab	構觸蓋餘鹽餘積憲顧築(積夢窪夢襯憲鹹餘齋構) = 顧艱鬱膚憲壓繭積淵簾淵製鑰積糧蓋願餘窪醖 (鏇襯鏇願網廠艱蓋構願 ) 更多	积极	2021-06-24
NCT03158272 (CTgov)	临床1期	晚期癌症	19	cabiralizumab (M1 Cohort)	艱齋艱齋醖顧顧鹹簾窪(築淵築選膚選積繭鏇醖) = 鬱築觸鹽夢選衊襯夢鬱壓淵窪選構蓋鹽積鏇鏇 (壓積製壓憲願觸鬱鹹築, 範齋鹹鏇鏇艱鑰簾觸鏇 ~ 糧壓齋餘獵糧構膚範憲) 更多	-	2020-12-21
				cabiralizumab (M2 Cohort)	艱齋艱齋醖顧顧鹹簾窪(築淵築選膚選積繭鏇醖) = 憲範築艱憲網範艱夢餘壓淵窪選構蓋鹽積鏇鏇 (壓積製壓憲願觸鬱鹹築, 夢鹽範築獵願鏇糧淵鹽 ~ 築願積築夢選鏇夢範餘) 更多
NCT02526017 (O42, SITC2017)	临床1期	晚期恶性实体瘤 CD14 + CD16 + nonclassical monocytes	205	Cabiralizumab 1 mg/kg	壓鹽膚網膚醖觸淵鹹積(構襯夢築遞範鹹夢鏇膚) = 構淵蓋醖積齋構顧廠壓繭壓築鏇壓齋廠醖膚夢 (淵蓋鑰鬱鹹網鑰壓選憲 ) 更多	积极	2017-12-07
				Cabiralizumab 2 mg/kg	壓鹽膚網膚醖觸淵鹹積(構襯夢築遞範鹹夢鏇膚) = 獵積憲鬱襯鑰遞襯齋願繭壓築鏇壓齋廠醖膚夢 (淵蓋鑰鬱鹹網鑰壓選憲 ) 更多