A Phase Ib/II , Multicenter, Open-Label Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Preliminary Anti-Tumor Effects of SC0245 in Combination With Irinotecan in Patients With ES-SCLC

This study is a single arm, multi-center, open label phase Ib/II study of SC0245 and Irinotecan combination therapy in subjects with extensive-stage small cell lung cancer (ES-SCLC) as a second therapy. This study will have three parts, phase 1 dose escalation (Part 1), phase 1 dose expansion (Part 2), and phase 2 combination therapy (Part 3).

开始日期2023-02-23

申办/合作机构

无锡智康弘义生物科技有限公司

CTR20223363 / Recruiting临床1/2期

SC0245片联合伊立替康在复发难治的广泛期小细胞肺癌患者中的一项开放性、多中心Ib/II期临床研究

Ib递增阶段主要目的：评估SC0245联合伊立替康在经标准治疗失败，或无标准治疗方案，或现阶段不适用标准治疗，或不能耐受标准治疗的晚期恶性实体瘤患者中的安全性和耐受性，确定联合治疗中SC0245的MTD及RP2D。次要目的：PK特征，初步抗肿瘤活性。Ib扩展阶段主要目的：评估SC0245联合伊立替康在一线含铂化疗（联合或不联合免疫治疗）失败或不耐受的广泛期SCLC患者中的安全性和耐受性；次要目的：PK特征，初步抗肿瘤活性。II期阶段主要目的：评估SC0245联合伊立替康在一线含铂化疗（联合或不联合免疫治疗）失败或不耐受的广泛期SCLC中的初步抗肿瘤活性。次要目的：安全性和耐受性。

开始日期2023-02-01

申办/合作机构

无锡智康弘义生物科技有限公司

CTR20210769 / Recruiting临床1期

一项开放、单臂的剂量递增和剂量扩展的临床研究，在晚期恶性实体瘤患者评估 SC0245 的安全性、耐受性、药代动力学特征与初步有效性

第一阶段（剂量递增阶段）：主要目的： -评估 SC0245 单药在晚期恶性实体瘤患者的安全性和耐受性； -确定 SC0245 的剂量限制毒性（Dose-Limiting Toxicity， DLT）和最大耐受剂量（MTD）或 II 期推荐剂量（RP2D）。次要目的： - 评估 SC0245 单药在晚期恶性实体瘤患者中的药代动力学（PK）特征； -评估 SC0245 单药在晚期恶性实体瘤患者中的初步抗肿瘤活性。第二阶段（剂量扩展阶段）主要目的：进一步评估 SC0245 单药在晚期恶性实体瘤患者的安全性和耐受性。次要目的： -进一步在多种特定肿瘤类型中初步评价 SC0245 单药在晚期恶性实体瘤患者中的抗肿瘤活性。 -进一步探索生物标记物与临床疗效之间的关系。

开始日期2021-06-29

申办/合作机构

石家庄智康弘仁新药开发有限公司

100 项与 SC-0245 相关的临床结果

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100 项与 SC-0245 相关的转化医学

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100 项与 SC-0245 相关的专利（医药）

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项与 SC-0245 相关的文献（医药）

2014-04-01·Investigational New Drugs3区 · 医学

Synthesis and in vitro characterization of ionone-based compounds as dual inhibitors of the androgen receptor and NF-κB

3区 · 医学

Article

作者: Jinming Zhou ; Jian Hui Wu ; Rongtuan Lin ; Weiguo Liu ; Guoyan Geng

Current therapeutic strategy for advanced prostate cancer is to suppress the androgen receptor (AR) signaling. However, lethal castration-resistant prostate cancer (CRPC) arises due to AR reactivation via multiple mechanisms, including mutations in the AR and cross-talk with other pathways such as NF-κB. We have previously identified two ionone-based antiandrogens (SC97 and SC245), which are full antagonists of the wild type and the clinically-relevant T877A, W741C and H874Y mutated ARs. Here, we discovered SC97 and SC245 also inhibit NF-κB. By synthesizing a series of derivatives of these two compounds, we have discovered a novel compound 3b that potently inhibits both AR and NF-κB signalling, including the AR F876L mutant. Compound 3b showed low micromolar antiproliferative activites in C4-2B and 22Rv1 cells, which express mutated ARs and are androgen-independent, as well as DU-145 and PC-3 cells, which exhibit constitutively activated NF-κB signalling. Our studies indicate 3b is effective against the CRPC cells.

2005-01-01·Journal of Immunotoxicology4区 · 医学

Screening New Drugs for Immunotoxic Potential: II. Assessment of the Effects of Selective and Nonselective COX-2 Inhibitors on Complement Activation, Superoxide Anion Production and Leukocyte Chemotaxis and Migration Through Endothelial Cells

4区 · 医学

ArticleOA

作者: John Mennear ; Sylvia M. Furst ; K. Nasir Khan ; Lian Fan ; Wendy J. Komocsar

Results from earlier experiments in our laboratories revealed that both selective and nonselective inhibitors of cyclooxygenase-2 possess little potential for decreasing in vitro phagocytosis by rat macrophages or canine neutrophils and no potential for decreasing in vivo phagocytosis by the intact murine immune system. We now report the results of studies to assess in vitro and ex vivo effects of the drugs on 1) canine complement activation, 2) generation of superoxide anion and hydrogen peroxide (oxidative burst) by canine neutrophils, and 3) leukocytic chemotaxis and transmigration through endothelial cell monolayers. In vitro concentrations of naproxen sodium, SC-236, SC-245, and SC-791 ranging from 0.1 to 10 muM were tested for their abilities to inhibit canine complement-mediated hemolysis of opsonized sheep erythrocytes and to block phorbol myristate acetate-induced oxidative burst in canine neutrophils. Both models responded to known inhibitory agents, leupeptin in the complement activation test and staurosporine in the superoxide anion assay. In contrast, tested nonsteroidal anti-inflammatory drugs produced only trivial changes in complement activation and superoxide anion production. Experiments on plasma and neutrophils isolated from dogs administered an experimental selective COX-2 inhibitor during a 28-day toxicology study revealed no evidence of drug-associated changes in complement activation or formation of superoxide anion. SC-791 reduced chemotaxis of canine leukocytes toward zymosan-activated dog plasma, but not toward leukotriene B(4). None of the other drugs tested significantly affected leukocytic chemotaxis. Ibuprofen, SC-245 and SC-791 but not SC-236, reduced transmigration of canine leukocytes through endothelial cell monolayers. Based on the results of these experiments and our earlier studies we have concluded that, although high (suprapharmacologic) concentrations of the drugs may induce in vitro evidence of apparent immunomodulation of the innate immune system, the findings are unlikely to represent a significant human health risk.

2005-01-01·Journal of Immunotoxicology4区 · 医学

Screening New Drugs for Immunotoxic Potential: I. Assessment of the Effects of Conventional Nonsteroidal Anti-Inflammatory Drugs and Selective COX-2 Inhibitors onIn VitroandIn VivoPhagocytic Activity

4区 · 医学

ArticleOA

作者: John H. Mennear ; K. Nasir Khan ; Kimber L. White ; Sylvia M. Furst ; Wendy J. Komocsar ; Vanessa L. Peachee

Although both experimental and clinical literature contain reports suggestive of associations between enhanced susceptibility to soft tissue infections and nonsteroidal anti-inflammatory drug (NSAID) use, the immunotoxicological potential of this class of therapeutic agents has not been thoroughly investigated. In consideration of the widespread clinical use of these agents, we have initiated studies of the interaction between NSAIDs (both nonselective and selective COX-2 inhibitors) and the immune system. This communication describes the conduct and results of assessments of the effects of NSAIDs on the in vitro phagocytic activity of rat macrophages and canine neutrophils and on the functional activity of the intact murine mononuclear phagocytic system. During in vitro experiments 0.1 to 10 muM concentrations of naproxen, indomethacin, and experimental selective COX-2 inhibitors, SC-236, SC-245 and SC-791, caused marginal, but statistically significant, reductions in phagocytic activity of resident rat peritoneal macrophages. The effects were consistently small and there was no evidence of concentration-response relationships. An in vitro concentration of 10 muM of either SC-236 or SC-791 was required to decrease phagocytosis by dog neutrophils. Repeated oral doses of either naproxen or SC-236 (3, 10, or 30 mg/kg twice daily for 3 days) were without effect on the intact phagocytic system of the mouse. A potential immunotoxicologic effect based on direct impairment of phagocytic processes seems an unlikely explanation for drug-induced susceptibility to infection reported earlier. However, the results of these experiments do not support an unequivocal conclusion relative to immunotoxicological potential of either conventional NSAIDs or selective COX-2 inhibitors. Further studies on other components of the immune system are needed to fully explore possible immunomodulatory effects of NSAIDs.

项与 SC-0245 相关的新闻（医药）

2023-01-16

·CPHI制药在线

新药 | ATR抑制剂：或合成致死新星，泰德制药TCC1727申报临床，罗氏超13亿美元引进

关注并星标CPHI制药在线1月11日，北京泰德制药股份有限公司1类新药「TCC1727片」的临床试验申请获CDE受理。据公开资料，TCC1727是选择性ATR激酶抑制剂，靶向作用于DNA损伤修复（DDR）通路重要激酶ATR 。 TCC1727作用机理为合成致死，通过抑制ATR功能，干扰DNA损伤修复，使癌细胞DNA损伤后得不到修复而死亡，同时ATR还参与调节肿瘤微环境，现有数据显示其对多个瘤种具有显著的抗肿瘤活性。 TCC1727 拟开发用于治疗非小细胞肺癌、小细胞肺癌、卵巢癌、三阴乳腺癌等多个癌种，重点针对 PD-(L)1 疗法、铂类化疗及 PARP 抑制剂治疗进展或耐药的癌症患者群体。 ATR，即共济失调毛细血管扩张和 Rad-3-相关蛋白，是一类蛋白丝氨酸/苏氨酸家族激酶，是DNA损伤修复通路的核心成员。而且，ATR 激酶是临床多种抗肿瘤疗法耐药的关键因子，包括铂类、吉西他滨及 PARP 抑制剂等重磅品种。合成致死是抗肿瘤药物开发热门领域，PARP是目前研发最快，且最成功的合成致死靶点。ATR被业界认为是继PARP后最有希望的合成致死靶点之一。 ATR和ATM是DNA损伤反应信号网络中的两种重要蛋白，被DNA损伤激活。ATR抑制剂通过阻断ATR介导的信号通路，可以扰乱DNA损伤修复。研究显示，在ATM缺失的肿瘤细胞中，ATR抑制剂可以产生合成致死效应，在导致ATM缺失肿瘤细胞死亡的同时，并不影响正常细胞。目前，全球已出现多款在研ATR抑制剂（详见下表），这些药物被开发作为单药疗法或联合其他药物用于治疗多种肿瘤，其中已有多款取得积极结果。值得一提的是，我国药企如英派药业、智康弘义也积极布局ATR抑制剂市场。 ♦ Camonsertib是一种选择性ATR口服小分子抑制剂，用于治疗具有特定合成致死基因组改变的肿瘤，包括 ATM（共济失调-毛细血管扩张突变）基因。2022 AACR大会上公布的1/2期临床试验结果显示：Camonsertib在晚期卵巢癌（n=20）队列中表现出可喜的活性。这些患者中90%曾经接受过PARP抑制剂治疗后出现耐药性，85%对含铂化疗耐药。Camonsertib在这一患者群体中的总缓解率达到25%，包括1名完全缓解和3名部分缓解。中位无进展生存期为35周。 ♦ Berzosertib是一种首创、强效、选择性ATR抑制剂，原名为VX-970，2017年默克从Vertex制药公司获得许可。由美国国家癌症研究所(NCI)开展并发表于国际医学期刊《癌症细胞》(Cancer Cell)的一项2期概念验证研究(NCT02487095)的结果证实：berzosertib联合化疗拓扑替康(TOP1抑制剂)治疗复发性小细胞肺癌(SCLC)患者疗效显著，客观缓解率(ORR)达36%(n=9/25)，达到了主要疗效终点。特别是，在病情缓解的铂耐药患者中，大部分患者表现出持久缓解。 ♦ M1774 是德国默克子公司EMDSerono 研究所研发的一种ATR激酶抑制剂，目前正处于单药或联合PARP抑制剂尼拉帕立治疗转移性或局部晚期不可切除实体瘤正的1期临床试验中。 ♦ Ceralasertib是阿斯利康开发的一款ATR抑制剂。2021 ASCO大会上公布的2期临床研究结果显示：ceralasertib联合度伐利尤单抗表现出有前景的抗肿瘤活性，尤其是在标准治疗（包括抗PD-1单抗治疗）失败的黑色素瘤患者中。不过，2022 ESMO乳腺癌大会上公布的奥拉帕利联合ceralasertib或WEE1抑制剂adavosertib二/三线治疗转移性三阴性乳腺癌（mTNBC）中的2期临床研究（VIOLETTE）结果显示：无论是否存在同源重组修复(HRR)基因突变和BRCA突变，与奥拉帕利单药治疗相比，奥拉帕利+ceralasertib未能改善mTNBC患者的无进展生存期（PFS）。 ♦ ART-0380 是由Artios Pharma 公司从美国MD Anderson 癌症中心和中国Shang PharmaInnovation获得许可开发的一种新的口服ATR抑制剂，2021年1月在美国启动单药或联合吉西他滨治疗晚期或转移性实体瘤的1/2a期临床研究。 ♦ elimusertib是拜耳开发的一款高度选择性强力ATR抑制剂。AACR大会上公布的1b期扩展临床研究显示：在143名携带不同DDR缺陷的晚期实体瘤患者中，elimusertib让约35%的患者疾病得到控制至少16周。在卵巢癌患者中，27.8%的患者临床获益时间超过6个月，其中包括对含铂化疗耐药并且接受过PARP抑制剂治疗的患者。在ATM表达缺失的患者中，部分缓解率为8.9%，55.9%的患者疾病稳定。 ♦ IMP9064是英派药业自主研发的一款ATR抑制剂。临床前数据显示，IMP9064对ATR具有高抑制活性，相比于其他激酶也展示了高选择性。同时，IMP9064在ATM缺陷型细胞系和移植瘤模型中都显示了良好的抗肿瘤活性和体内活性，具有获得更宽的治疗窗口、以及单药长期用药和联合用药的潜力。 ♦ SC0245是国内首个获批临床的ATR抑制剂，目前正在开展一项开放、单臂的1a/1b期研究。据悉，SC0245在临床前研究中展现出良好的安全性，在体内体外药效均优于同靶点产品AZD6738。 ♦ ATG-018是一款由德琪医药研发团队自主开发的作用于ATR激酶的口服、强效、选择性小分子抑制剂。2022 AACR大会上公布的临床前研究结果显示：ATG-018在多个具有同源重组缺乏的实体瘤/血液肿瘤的体内模型和体外试验中显示了单药疗效。而且，研究还发现了多个与ATG-018敏感性相关的基因表达变化，这些差异基因具有成为预测性生物标志物的潜力。整体来看，ATR抑制剂的研发还处于早期阶段，但其市场潜力已被越来越多的企业看重。值得一提的是，去年6月，罗氏与Repare Therapeutics就Camonsertib达成全球许可和合作协议，交易金额超13亿美元。期待未来ATR抑制剂可以早日问世，造福广大肿瘤患者。扫描下方二维码，发送“新年快乐”，领取新年好礼来源：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~

AACR会议临床结果临床2期临床申请

100 项与 SC-0245 相关的药物交易

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研发状态

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适应症	最高研发状态	国家/地区	公司	日期
小细胞肺癌复发	临床2期	中国	无锡智康弘义生物科技有限公司	2023-02-23
晚期恶性实体瘤	临床1期	中国	石家庄智康弘仁新药开发有限公司	2021-06-29

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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


NCT05731518 (ASCO2024)	临床1/2期	小细胞肺癌复发 ATR	15	SC0245 80mg QD	(糧糧製鹽蓋獵築鏇鏇範) = 淵構願鹽艱蓋築膚選廠鬱製製範齋蓋觸淵餘遞 (壓範襯壓淵淵構廠積齋 )	积极	2024-05-24
				SC0245 120mg QD	(糧糧製鹽蓋獵築鏇鏇範) = 糧獵製衊鬱餘齋襯膚餘鬱製製範齋蓋觸淵餘遞 (壓範襯壓淵淵構廠積齋 )