主要目的：根据受试者的客观缓解率（ORR），疾病控制率（DCR），缓解持续时间（DOR）和无进展生存期（PFS）, 初步评估AST-3424单药治疗HCC等恶性肿瘤的疗效。次要目的：评估单药治疗肝细胞癌等恶性肿瘤的安全性和耐受性，探讨肿瘤组织经免疫组织化学确定的AKR1C3表达与疗效之间的关系。探索性目的：评估受试者接受单药治疗后的疼痛缓解程度及止痛药使用变化。

开始日期2022-06-23

申办/合作机构

深圳艾欣达伟医药科技有限公司初创企业

CTR20201908 / Recruiting临床1期

评价AST-3424 治疗复发或难治性急性淋巴细胞白血病患者的安全性、耐受性、药代动力学、初步疗效以及疗效与AKR1C3 酶表达相关性的临床研究

主要目的：评估AST-3424静脉给药的安全性和耐受性；评估AST-3424及其代谢产物的药代动力学特征；评估ALL受试者接受AST-3424单药治疗的给药方案；次要目的：初步评估AST-3424单药治疗复发或难治性ALL的血液学缓解情况，判定标准为ORR= CR+PR（其中CR包括CR和CRi）；评估患者的总生存期（OS）；评估患者的无进展生存期（PFS）（PFS定义为从首次用药开始到疾病进展或任何原因导致的死亡的时间）；评估CR/CRi患者的微小残存病变（MRD）的阴性率（MRD阴性定义为流式细胞术检测< 0.01%）；评估CR/CRi患者微小残存病变（MRD）首次达到阴性的时间；评估CR/CRi患者MRD阴性持续的时间（从达到CR/CRi后MRD首次评估阴性到MRD转为阳性或CR/CRi后复发的最早日期时间）；探讨患者外周血和骨髓中经PCR-荧光探针法确定的AKR1C3酶的表达与疗效之间的关系。探索性目的：探索DNA损伤修复相关基因突变的表达。

开始日期2021-04-06

申办/合作机构

深圳艾欣达伟医药科技有限公司初创企业

NCT04315324 / Recruiting临床2期IIT

A Phase II Study of AKR1C3-Activated Prodrug OBI-3424 (OBI-3424) in Patients With Relapsed/Refractory T-Cell Acute Lymphoblastic Leukemia (T-ALL)

This phase II trial studies how well OBI-3424 works in treating patients with T-cell acute lymphoblastic leukemia that has come back (relapsed) or does not response to treatment (refractory). Drugs used in chemotherapy, such as OBI-3424, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. OBI-3424 may reduce the amount of leukemia in the body.

开始日期2021-02-08

申办/合作机构

National Cancer Institute

100 项与 AST-3424 相关的临床结果

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100 项与 AST-3424 相关的转化医学

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100 项与 AST-3424 相关的专利（医药）

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项与 AST-3424 相关的文献（医药）

2023-08-01·British journal of cancer

Phase 1 dose-escalation study evaluating the safety, pharmacokinetics, and clinical activity of OBI-3424 in patients with advanced or metastatic solid tumors.

Article

作者: Hsu, Pei ; Pearce, Tillman E. ; Wesolowski, Robert ; Verschraegen, Claire F. ; Shia, Chi-Sheng ; Tsimberidou, Apostolia Maria

BACKGROUND:

Report of a Phase 1 dose-escalation study of OBI-3424 monotherapy in patients with advanced solid tumors (NCT03592264).

METHODS:

A classic 3 + 3 design was used to determine the maximum tolerated dose and recommended Phase 2 dose (RP2D) of OBI-3424 administered intravenously, as a single agent, at doses of 1, 2, 4, 6, 8, or 12 mg/m² (days 1 and 8 of a 21-day cycle, Schedule A) or 8, 10, 12, or 14 mg/m² (day 1 of a 21-day cycle, Schedule B).

RESULTS:

Dose-limiting hematologic toxicities at 12 mg/m² in Schedule A led to dose and schedule modifications (Schedule B). In Schedule B, maximum tolerated dose was not reached at the maximum dose tested (14 mg/m²). Grade ≥3 anemia was noted in 3/6 patients treated at 14 mg/m²; the RP2D was 12 mg/m² (Schedule B). Grade ≥3 treatment-emergent adverse events were experienced by 19/39 (49%) and included anemia (41%) and thrombocytopenia (26%); three patients experienced serious treatment-emergent adverse events (grade ≥3 anemia and thrombocytopenia). One patient had a partial response and 21/33 (64%) had stable disease.

CONCLUSIONS:

The RP2D is 12 mg/m² once every 3 weeks. OBI-3424 was well tolerated; dose-dependent, noncumulative thrombocytopenia and anemia were dose-limiting.

2023-06-01·Journal of pharmacological sciences

A novel AKR1C3 specific prodrug AST-3424 and its combination therapy in hepatocellular carcinoma

Article

作者: Qin, Shukui ; Zheng, Xia ; Zhang, Yu ; Xun, Chen

OBJECTIVE:

AST-3424 is a novel specific aldo-keto reductase 1C3 (AKR1C3) prodrug that releases a DNA alkylating reagent upon reduction by AKR1C3. This study aimed to evaluate the efficacy and safety of AST-3424 in patient-derived tumor xenograft (PDTX) model and orthotopic model against hepatocellular carcinoma (HCC).

MATERIALS AND METHOD:

PDTX models derived from three HCC patients and orthotopic mice models using HepG2 cells were developed. The mice were treated with AST-3424 alone or combined with other drugs (oxaliplatin, apatinib, sorafenib and elemene in PDTX models, oxaliplatin and 5- fluorouracil in orthotopic models). The tumor volume and weight, as well as the mice weight were assessed. The liver tumor and transplanted tumor were removed for histological, immunohistochemical and Western blot detection in orthotopic model experiments.

RESULTS:

AST-3424 could inhibit tumor growth in HCC PDTX models and orthotopic models, with no difference in safety compared with other marketed drugs, and the drug combination did not increase toxicity. The inhibitory effect of combination treatment was more obvious than which used alone. The reduction of AKR1C3 expression was negatively correlated with AST-3424 dose.

CONCLUSION:

AST-3424 had a promising effect against HCC in PDTX model and orthotopic model with good safety. It could promote the sensitivity of other drugs without increasing toxicity. Clinical trials are warranted to further certify its antitumor effect and safety.

2023-01-01·American journal of cancer research

Erratum: A novel selective AKR1C3-activated prodrug AST-3424/OBI-3424 exhibits broad anti-tumor activity.

作者: Wang, Chun-Chung ; Qi, Tianyang ; Meng, Fanying ; Jung, Donald ; Hsu, Ren-Yu ; Duan, Jianxin ; Hsieh, Yin-Cheng ; Li, Wan-Fen ; Shia, Chi-Sheng

[This corrects the article on p. 3645 in vol. 11, PMID: 34354865.].

项与 AST-3424 相关的新闻（医药）

2024-06-13

·PipelineReview

OBI Pharma Announces Phase 1/2 Study Initiation for OBI-992, a TROP2-Targeted Antibody-Drug Conjugate (ADC) for Cancer Therapy

Clinical trial to evaluate the safety and efficacy of OBI-992 in advanced solid tumors. TAIPEI, Taiwan I June 12, 2024 I OBI Pharma, a clinical-stage oncology company (4174.TWO), today announced the initiation of a Phase 1/2 clinical trial of OBI-992, an antibody-drug conjugate (ADC) targeting TROP2 (Trophoblast cell-surface antigen 2), an antigen overexpressed in multiple tumor types. OBI plans to enroll patients with advanced solid tumors, including non-small cell lung cancer (NSCLC), small cell lung cancer (SCLC), gastric cancer (GC), and other potential cancers. The objective of the trial is to verify the safety, pharmacokinetics, and preliminary efficacy profile of OBI-992 in these patient populations. OBI Pharma’s Chief Medical Officer, M. Wayne Saville, M.D., noted, “Based on our preclinical data, OBI-992 has several important advantages over other TROP2 ADCs in development; including high serum stability, excellent bystander effect, potential ability to overcome drug resistance, and outstanding activity in animal and organoid models of cancer 1 , 2 , 3 . We look forward to investigating this potential best-in-class TROP2 ADC in the clinic. Leia Tsimberidou MD, of MD Anderson Cancer Center in Houston, TX. USA is the lead investigator for the study.” Heidi Wang, Ph.D., OBI Pharma’s Chief Executive Officer, added, “We are excited to initiate this first in human study of OBI-992. This is an important company milestone and highlights our commitment to building and strengthening the novel OBI Pharma oncology pipeline. We thank the patients and the investigators for their efforts and dedication.” About OBI-992 OBI-992 is a TROP2-targeted antibody-drug conjugate (ADC) that carries a potent topoisomerase I inhibitor payload (exatecan) proven to kill tumor cells. TROP2 is highly expressed in a variety of solid tumors such as lung, breast, ovarian, gastric, and other cancers, rendering it an ideal target for cancer therapy. OBI-992 uses a unique hydrophilic, enzyme-cleavable linker that is stable in circulation but releases the cytotoxic payload inside tumor cells. In preclinical animal models, OBI-992 demonstrated remarkable antitumor activity, improved pharmacokinetic characteristics, and a favorable safety profile relative to comparator ADCs. The TROP2 targeting antibody was in-licensed from Biosion, Inc. www.Biosion.com , in December 2021. OBI Pharma owns ex-China commercial rights for OBI-992. About OBI Pharma OBI Pharma, Inc., is a clinical stage oncology company that is headquartered in Taiwan and established in 2002. Its mission is to develop novel cancer therapeutic agents for patients with high unmet medical needs. The company’s novel first-in-class immuno-oncology portfolio targeting Globo H includes: two Globo H active immunotherapy vaccines, adagloxad simolenin (formerly OBI-822) and OBI-833. Using the company’s unique ADC platforms, including GlycOBI™, OBI created its novel ADC pipeline which includes OBI-992, OBI-902 and OBI-904, targeting TROP2 and Nectin-4, respectively. OBI’s pipeline also includes the first-in-class AKR1C3-targeted small-molecule prodrug OBI-3424, which selectively releases a potent DNA-alkylating antitumor agent in the presence of the aldo-keto reductase 1C3 (AKR1C3) enzyme. Additional information can be found at www.obipharma.com . GlycOBI™ is a trademark of OBI Pharma, Inc. 1 , 2 , 3 : AACR Annual Meeting 2024 Abstracts online. OBI Pharma, Inc. Taipei, Taiwan. https://www.obipharma.com/zh-hant/news-zh-hant/poster-presentations-at-the-aacr-2024-annual-meeting-for-obi-992-and-glycobi-adc-platform/ SOURCE: OBI Pharma

免疫疗法AACR会议抗体药物偶联物疫苗临床申请

2024-06-12

·BioSpace

OBI Pharma Announces Phase 1/2 Study Initiation for OBI-992, a TROP2-Targeted Antibody-Drug Conjugate (ADC) for Cancer TherapyClinical trial to evaluate the safety and efficacy of OBI-992 in advanced solid tumors.

TAIPEI, Taiwan, June 12, 2024 (GLOBE NEWSWIRE) -- OBI Pharma, a clinical-stage oncology company (4174.TWO), today announced the initiation of a Phase 1/2 clinical trial of OBI-992, an antibody-drug conjugate (ADC) targeting TROP2 (Trophoblast cell-surface antigen 2), an antigen overexpressed in multiple tumor types. OBI plans to enroll patients with advanced solid tumors, including non-small cell lung cancer (NSCLC), small cell lung cancer (SCLC), gastric cancer (GC), and other potential cancers. The objective of the trial is to verify the safety, pharmacokinetics, and preliminary efficacy pro OBI-992 in these patient populations. OBI Pharma's Chief Medical Officer, M. Wayne Saville, M.D., noted, “Based on our preclinical data, OBI-992 has several important advantages over other TROP2 ADCs in development; including high serum stability, excellent bystander effect, potential ability to overcome drug resistance, and outstanding activity in animal and organoid models of cancer 1, 2,3. We look forward to investigating this potential best-in-class TROP2 ADC in the clinic. Leia Tsimberidou MD, of MD Anderson Cancer Center in Houston, TX. USA is the lead investigator for the study.” Heidi Wang, Ph.D., OBI Pharma’s Chief Executive Officer, added, “We are excited to initiate this first in human study of OBI-992. This is an important company milestone and highlights our commitment to building and strengthening the novel OBI Pharma oncology pipeline. We thank the patients and the investigators for their efforts and dedication.” About OBI-992 OBI-992 is a TROP2-targeted antibody-drug conjugate (ADC) that carries a potent topoisomerase I inhibitor payload (exatecan) proven to kill tumor cells. TROP2 is highly expressed in a variety of solid tumors such as lung, breast, ovarian, gastric, and other cancers, rendering it an ideal target for cancer therapy. OBI-992 uses a unique hydrophilic, enzyme-cleavable linker that is stable in circulation but releases the cytotoxic payload inside tumor cells. In preclinical animal models, OBI-992 demonstrated remarkable antitumor activity, improved pharmacokinetic characteristics, and a favorable safety pro to comparator ADCs. The TROP2 targeting antibody was in-licensed from Biosion, Inc. , in December 2021. OBI Pharma owns ex-China commercial rights for OBI-992. About OBI Pharma OBI Pharma, Inc., is a clinical stage oncology company that is headquartered in Taiwan and established in 2002. Its mission is to develop novel cancer therapeutic agents for patients with high unmet medical needs. The company’s novel first-in-class immuno-oncology portfolio targeting Globo H includes: two Globo H active immunotherapy vaccines, adagloxad simolenin (formerly OBI-822) and OBI-833. Using the company’s unique ADC platforms, including GlycOBI™, OBI created its novel ADC pipeline which includes OBI-992, OBI-902 and OBI-904, targeting TROP2 and Nectin-4, respectively. OBI’s pipeline also includes the first-in-class AKR1C3-targeted small-molecule prodrug OBI-3424, which selectively releases a potent DNA-alkylating antitumor agent in the presence of the aldo-keto reductase 1C3 (AKR1C3) enzyme. Additional information can be found at . GlycOBI™ is a trademark of OBI Pharma, Inc. 1, 2,3: AACR Annual Meeting 2024 Abstracts online. OBI Pharma, Inc. Taipei, Taiwan. Forward-Looking Statements Statements included in this press release that are not a description of historical facts are forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. Such forward-looking statements include, but are not limited to, statements about future clinical trials, results and the timing of such trials and results. Such risk factors are identified and discussed from time to time in OBI Pharma’s reports and presentations, including OBI Pharma’s filings with the Taiwan Securities and Futures Bureau. COMPANY CONTACT: Kevin Poulos Chief Business Officer OBI Pharma, Inc. 1.619.537.7698 Ext. 102 kpoulos@obipharmausa.com 115011台北市南港区忠孝东路七段508号6楼 6F., No. 508, Sec 7, Zhongxiao E. R., Nangang Dist., Taipei 115011, Taiwan R.O.C. OBI PHARMA台灣浩鼎

免疫疗法AACR会议

2024-05-16

·药渡

小分子新药创联协会&艾欣达伟 | 小分子创新药院士及专家论坛第六期

1深圳市坪山区小分子新药创联协会深圳市坪山区小分子新药创联协会在南方科技大学坪山生物医药研究院院长张绪穆院士、深圳兴湾生物首席科学家张丹院士、深圳万乐药业袁庆总经理、深圳艾欣达伟医药段建新董事长、深圳华先医药叶伟平董事长等坪山区小分子新药相关开发企业的发起下，于2023年4月顺利创办成立。协会会员将以小分子创新药企业以及该领域相关专家为主，并将以联盟的形式运作。协会以“创制小分子创新药、临床研发、高端原料药、高端制剂、创新技术”为发展目标，将扎根于深圳坪山，为资源共享做出积极贡献，为小分子药物研发公司争取更多的资源，为坪山以及大湾区发展小分子创新药提供一个新的模式，努力实现“医药创新产业链大融合”的目标宗旨。2深圳艾欣达伟医药科技有限公司深圳艾欣达伟医药科技有限公司是一家专注于小分子靶向偶联创新药物研发的生物医药科技企业。公司坚持通过原始创新技术，围绕着全新靶点，自主开发以临床急需为导向的具有全球知识产权的抗肿瘤药物。公司首发项目AST-3424在美国获得肝癌和白血病两个适应症的孤儿药认定，并分别于中美进入临床II期，到目前为止的临床数据表明AST-3424安全有效；AST-001项目正在国内开展临床I期，显示出良好的安全性和有效性，后续将进一步针对胰腺癌等适应症开展临床研究；AST-006针对PARP抑制剂耐药的适应症已经获得中国临床试验默示许可；还有多个项目处于临床前注册研究阶段。3第六期主讲嘉宾孙宏斌重庆中国药科大学创新研究院院长（往下可滑动）1989年毕业于吉林大学化学系，1995年于中国药科大学获得博士学位。现任重庆中国药科大学创新研究院院长、中国药学会药物化学专业委员会副主任委员。主要研究方向是代谢与免疫调控新药发现。主持研制的4个1类新药实现了成果转化，其中，抗血栓新药维卡格雷已向美国FDA提交新药上市申请(NDA)。在PNAS,J.Am.Chem.Soc.,Journal ofMedicinal Chemistry等期刊发表SCI论文200余篇，获授权专利42项。主持国家自然科学基金重点项目、国家自然科学基金委医学部“十三五”和“十四五”药物学发展规划等基金项目20余项。蔡绮纯祈福医院肿瘤中心主任祈福医院肿瘤中心主任祈福医院肿瘤中心主任，学科带头人，主任医师。广东省肿瘤精准与综合治疗学术委员会副主委，广东省临床医学学会常委，广东省抗癌协会血液肿瘤专业委员会委员。侧重肿瘤免疫微环境的研究，于2002年开始提出“肿瘤整体免疫治疗理论”。擅长恶性淋巴瘤、免疫相关肿瘤的综合治疗。在《Nature Medicine》等知名杂志上发表论文40多篇，参与7个省级以上基金以及多项国际、国内临床药物试验研究。李子刚北京大学深圳研究生院化学生物学与生物技术学院执行院长北京大学深圳研究生院化学生物学与生物技术学院执行院长，教授/博士生导师。致力于在化学和生物交叉领域用化学方法解决生物学问题，在针对人类癌症的多肽药物研发和感染性疾病的小分子药物筛选等方面做出了一系列成果，为探索更加有效的药物前体奠定基础，并与医院展开临床前期研究，为基于稳定多肽的抗肿瘤药物开发提供宝贵的临床研究基础。在J.Am.Chem.Soc、Sci.Adv.、ACS Nano、Autophagy、ccs chem.、 Nat.chem.Biol.、cancer Res.、Angew.Chem.lnt.Ed、Chem.Sci.等国际知名期刊上共计发表论文180余篇，申请发明专利七十余项，已获得发明专利授权二十余项。姜宏梁武汉宏韧生物医药股份有限公司创始人&董事长（往下可滑动）华中科技大学教授，博士生导师，武汉宏韧生物医药股份有限公司，创始人，董事长。从沈阳药科大学获得本科学位，北京协和医学院获得硕士学位，美国亚利桑那大学获得博士学位，并曾在美国西北太平洋国家实验室从事博士后研究工作及在美国Covance lnc.生物分析部工作多年。曾主持多项国家自然科学基金。为国家科学技术奖励评审、“重大新药创制”科技重大专项及国家自然科学基金评审专家。参与国家药监局颁布的多个行业指导原则的讨论与制定。目前，已发表SCI收录论文50多篇。带领团队完成了1000多个仿制药生物等效性的生物分析检测项目、200多个创新药临床生物分析研究项目及200多个非临床药代动力学研究项目。4活动预告活动主题：小分子新药研发机遇和挑战直播时间：2024年5月24日 14:00-17:00活动议程：14：00-14：10 开场及嘉宾介绍14：10-14：20 政府领导致辞14：20-14：30 小分子新药创联协会及院士专家论坛介绍14：30-14：55 主题讲座：靶向核受体的抗肝纤维化新药发现研究（孙宏斌教授，重庆中国药科大学创新研究院院长）14：55-15：20 主题讲座：新药开发中临床前用药环节探讨（蔡绮纯主任，祈福医院肿瘤中心主任）15：20-15：45 主题讲座：稳定多肽的生物医药应用（李子刚教授，北京大学深圳研究生院化学生物学与生物技术学院执行院长）15：45-15：55 茶歇15：55-16：20 主题讲座：生物分析在临床和非临床PK研究中的关键考虑因素及应用示例（姜宏梁教授，武汉宏韧生物医药股份有限公司创始人&董事长）16：20-16：45 主题讲座：麓鹏制药研发管线进展简介（胡龙飞副总裁，广州麓鹏制药有限公司副总裁）16：45-17：00 讨论环节5参与方式1、视频号预约2、进交流群3、遇到问题与我们联系电话：180 0138 3271（同微信）邮箱：xuanya.wang@pharmacodia.com6关于公司药渡经纬信息科技（北京）有限公司（简称“药渡”)，成立于2013，是国内领先的医药研发垂直领域专业数据信息情报服务公司。我们构建了强大的医药大数据聚合系统，具备深度趋势预测和机会推荐的数据挖掘能力，以医药竞争情报数据、深度分析咨询服务、研发资源和品牌推广服务等赋能医药行业客户药物研发创新能力和行业竞争力。

临床3期孤儿药临床1期临床2期引进/卖出

100 项与 AST-3424 相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
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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
急性髓性白血病	临床2期	中国	深圳艾欣达伟医药科技有限公司初创企业	2022-06-23
膀胱癌	临床2期	中国	深圳艾欣达伟医药科技有限公司初创企业	2022-06-23
结直肠癌	临床2期	中国	深圳艾欣达伟医药科技有限公司初创企业	2022-06-23
子宫内膜癌	临床2期	中国	深圳艾欣达伟医药科技有限公司初创企业	2022-06-23
食管癌	临床2期	中国	深圳艾欣达伟医药科技有限公司初创企业	2022-06-23
结外NK-T细胞淋巴瘤	临床2期	中国	深圳艾欣达伟医药科技有限公司初创企业	2022-06-23
肝细胞癌	临床2期	中国	深圳艾欣达伟医药科技有限公司初创企业	2022-06-23
高危骨髓增生异常综合征	临床2期	中国	深圳艾欣达伟医药科技有限公司初创企业	2022-06-23
非小细胞肺癌	临床2期	中国	深圳艾欣达伟医药科技有限公司初创企业	2022-06-23
外周T细胞淋巴瘤	临床2期	中国	深圳艾欣达伟医药科技有限公司初创企业	2022-06-23

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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


NCT06239155 (ASCO2024)	临床1期	晚期恶性实体瘤 AKR1C3 expression	21	AST-3424 8 mg/m2	(簾襯壓襯選壓鏇窪糧窪) = 夢蓋衊觸觸醖鹽鑰選襯餘鏇淵鏇製簾膚網選鏇 (窪餘鏇築鹽齋醖廠壓積 ) 更多	积极	2024-05-24
NCT03592264 (Pubmed)	临床1期	转移性实体瘤	39	OBI-3424	遞獵範憲襯鹹繭壓窪憲(築艱憲齋齋繭夢獵鏇壓) = 壓齋壓繭積積憲簾獵鏇築網繭壓網顧夢繭憲築 (鹽製鑰襯繭製糧網願淵 )	-	2023-05-12
NCT03592264 \| NCT04315324 (AACR2022)	临床1/2期	胰腺腺癌 \| HR阳性/HER2低表达实体瘤 \| 难治性 T 急性淋巴细胞白血病	-	OBI-3424	淵醖艱製築網鏇衊鹽鹽(膚顧遞淵積獵願鏇製觸) = 醖鏇淵觸顧醖鑰窪觸構顧繭構餘鏇餘餘鹹繭壓 (繭鹽窪製糧壓淵積選壓 )	-	2022-06-15
NCT03592264 \| NCT04315324 (AACR2022)	临床1/2期	胰腺腺癌 \| HR阳性/HER2低表达实体瘤 \| 难治性 T 急性淋巴细胞白血病	-	Pembrolizumab	淵醖艱製築網鏇衊鹽鹽(膚顧遞淵積獵願鏇製觸) = 製夢糧願鑰壓鬱艱製艱顧繭構餘鏇餘餘鹹繭壓 (繭鹽窪製糧壓淵積選壓 )	-	2022-06-15
NCT03592264 (ASCO2022)	临床1期	转移性实体瘤	39	OBI-3424	淵築鏇鹽艱憲獵膚築製(獵觸膚壓構淵淵網積憲) = 夢鬱襯觸鹹窪選願膚蓋艱範願糧壓範鹹餘淵獵 (膚製齋願蓋鏇糧蓋齋繭 ) 更多	-	2022-06-02