Mipletamig(Mipletamig) - 药物靶点：CD123 x CD3_在研适应症：CD123阳性急性髓性白血病_专利_临床

概要

基本信息

药物类型

双特异性T细胞结合器

别名

APVO-436、APVO436

靶点

CD123 x CD3

作用方式

抑制剂、刺激剂

作用机制

CD123抑制剂(白细胞介素-3受体α亚基抑制剂)、CD3刺激剂(T细胞表面糖蛋白CD3复合体刺激剂)

治疗领域

肿瘤血液及淋巴系统疾病

在研适应症

CD123阳性急性髓性白血病

非在研适应症

骨髓增生异常综合征难治性急性髓细胞白血病

原研机构

Aptevo Therapeutics, Inc.

在研机构

Aptevo Therapeutics, Inc.

非在研机构

Aptevo Research & Development LLC

权益机构-

最高研发阶段临床1期

首次获批日期-

最高研发阶段(中国)-

特殊审评孤儿药 (美国)

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结构/序列

Sequence Code 319660465

来源: *****

关联

3

项与 Mipletamig 相关的临床试验

NCT04973618

/ Withdrawn临床1期

Phase 1B Study of APVO436 in Combination With Venetoclax and Azacitidine in Elderly or Unfit Patients With Newly Diagnosed Acute Myeloid Leukemia (AML)

The goal of this Phase IB study is to evaluate the safety and tolerability of APVO436 in naïve elderly unfit patients with newly diagnosed primary AML at the RP2D level when it is used as an adjunct to the standard of care and obtain a preliminary assessment of the anti-leukemia activity of an APVO436-containing combination therapy.
Study Objectives:
- Primary Objective: Evaluate the safety and tolerability of APVO436 at the RP2D level when it is used as an adjunct to the standard of care (venetoclax and azacitidine).
- Secondary Objectives:
* Obtain a preliminary assessment of the anti-leukemia activity of APVO436-containing experimental triple drug combination therapy modalities.
* Determine pharmacodynamics (PD) of APVO436, including changes in CD123 antigen density and measures of T cell number and function over time.
* Determine correlations between response and MRD level and cytogenetic and molecular genetic profiles.

开始日期2025-01-01

申办/合作机构

Aptevo Therapeutics, Inc.

NCT06634394

/ Recruiting临床1期

A Phase 1b/2 Open-Label Study of APVO436 in Combination With Venetoclax and Azacitidine in Patients With Newly Diagnosed Acute Myeloid Leukemia (AML)

A multi-center, open-label, dose-finding study of five dose levels of APVO436 in combination with venetoclax and azacitidine (ven/aza) in adult patients with newly diagnosed, CD123+ AML.

开始日期2024-10-01

申办/合作机构

Aptevo Therapeutics, Inc.

NCT03647800

/ Unknown status临床1期

Phase 1B Open-Label, Dose-Escalation and Dose-Expansion Study of APVO436 in Patients With Relapsed or Refractory Acute Myeloid Leukemia (AML) or High-Grade Myelodysplastic Syndrome (MDS)

The primary objective of the Phase 1 part of the study is to determine the recommended dose of APVO436 administered intravenously to patients with AML or MDS. The primary objective of the Phase 1b part of the study is to evaluate the clinical activity of APVO436 in patients with AML or MDS.
APVO436 is being studied in this Phase 1b, open-label, multi-center, two-part dose-escalation/dose expansion study to evaluate the safety, pharmacokinetic/pharmacodynamic (PK/PD), and clinical activity of APVO436 in patients with AML and MDS. The study will be conducted in 2 parts. The first part of this Phase 1B study is an open-label, multiple dose ascending dose escalation phase to determine the recommended dose (RP2D) level of APVO436 for future Phase 2 studies. The goal of the dose expansion phase of the study (Part 2) is to (i) evaluate the safety and tolerability of APVO436 at the RP2D level when it is used as an adjunct to the standard of care and (ii) obtain a preliminary assessment of the anti-leukemia activity of APVO436-containing experimental monotherapy and combination therapy modalities.
Study Objectives for Dose Escalation Phase
* Primary Objectives are to:
1. Determine the RP2D level of APVO436 administered intravenously (IV) in patients with AML or MDS, and
2. Evaluate the safety and tolerability of APVO436 at the RP2D level when it is used as an adjunct to the standard of care and obtain a preliminary assessment of the anti-leukemia activity of APVO436-containing experimental monotherapy and combination therapy modalities.
* Secondary Objectives are to:
1. Define the safety profile and immunogenicity of APVO436; to determine the PK/PD of APVO436; to evaluate the clinical activity of APVO436 in AML and MDS patients.
2. Further evaluate the safety profile and immunogenicity of APVO436 and the PK/PD of APVO436 and the relationship between PK/PD and clinical response.
Study Objectives for Dose Expansion Phase
* Primary Objective is to evaluate the safety and tolerability of APVO436 at the RP2D level when it is used as an adjunct to the standard of care.
* Secondary Objective is to obtain a preliminary assessment of the anti-leukemia activity of APVO436-containing experimental monotherapy and combination therapy modalities.

开始日期2018-12-13

申办/合作机构

Aptevo Research & Development LLC

100 项与 Mipletamig 相关的临床结果

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100 项与 Mipletamig 相关的转化医学

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100 项与 Mipletamig 相关的专利（医药）

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3

项与 Mipletamig 相关的文献（医药）

Cancers2区 · 医学

A Clinical Phase 1B Study of the CD3xCD123 Bispecific Antibody APVO436 in Patients with Relapsed/Refractory Acute Myeloid Leukemia or Myelodysplastic Syndrome

2区 · 医学

ArticleOA

作者: Lin, Tara L. ; Shahidzadeh, Anoush ; Mims, Alice S. ; Shami, Paul J. ; Patel, Prapti ; Cogle, Christopher R. ; Lee, Cynthia ; Cull, Elizabeth ; Watts, Justin ; Uckun, Fatih M.

APVO436 is a recombinant T cell-engaging humanized bispecific antibody designed to redirect host T cell cytotoxicity in an MHC-independent manner to CD123-expressing blast cells from patients with hematologic malignancies and has exhibited single-agent anti-leukemia activity in murine xenograft models of acute myeloid leukemia (AML). In this first-in-human (FIH) multicenter phase 1B study, we sought to determine the safety and tolerability of APVO436 in R/R AML/myelodysplastic syndrome (MDS) patients and identify a clinically active recommended phase 2 dose (RP2D) level for its further clinical development. A total of 46 R/R AML/MDS patients who had failed 1–8 prior lines of therapy received APVO436 as weekly intravenous (IV) infusions at 10 different dose levels, ranging from a Minimum Anticipated Biological Effect Level (MABEL) of 0.3 mcg to 60 mcg. APVO436 exhibited a favorable safety profile with acceptable tolerability and manageable drug-related adverse events (AEs), and its maximum tolerated dose (MTD) was not reached at a weekly dose of 60 mcg. The most common APVO436-related AEs were infusion-related reactions (IRR) occurring in 13 (28.3%) patients and cytokine release syndrome (CRS) occurring in 10 (21.7%). The single dose RP2D level was identified as 0.2 mcg/kg. Preliminary efficacy signals were observed in both AML and MDS patients: Prolonged stable disease (SD), partial remissions (PR), and complete remissions (CR) were observed in R/R AML patients as best overall responses to APVO436 at the RP2D level. Three of six evaluable MDS patients had marrow CRs. The safety and preliminary evidence of efficacy of APVO436 in R/R AML and MDS patients warrant further investigation of its clinical impact potential.

Frontiers in Oncology3区 · 医学

Post-hoc Analysis of Pharmacodynamics and Single-Agent Activity of CD3xCD123 Bispecific Antibody APVO436 in Relapsed/Refractory AML and MDS Resistant to HMA or Venetoclax Plus HMA

3区 · 医学

ArticleOA

作者: Cogle, Christopher R ; Mims, Alice ; Wang, Eunice ; Lin, Tara L ; Shahidzadeh, Anoush ; Shami, Paul ; Patel, Prapti ; Watts, Justin ; Uckun, Fatih M ; Lee, Cynthia ; Cull, Elizabeth

APVO436 is a recombinant bispecific antibody designed to direct host cytotoxic T-cells to CD123-expressing blast cells in patients with hematologic malignancies. APVO436 showed promising tolerability and single-agent activity in relapsed or refractory (R/R) acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS). The primary purpose of this post-hoc analysis was to evaluate the therapeutic and pharmacodynamic effects of APVO436 in 14 R/R AML/MDS patients who had failed treatment with hypomethylating agents (HMA) or venetoclax plus HMA prior to being enrolled in the APVO436 Phase 1 dose-escalation study that was recently completed. Eight of these 14 patients had R/R AML and had failed treatment with HMA (N=2) or venetoclax plus HMA (N=6). The remaining 6 patients had R/R MDS and had also failed treatment with HMA (N=5) or venetoclax plus HMA (N=1). They were treated with APVO436 at submicrogram dose levels >0.08 mcg/kg that were active in preclinical NOD/SCID mouse xenograft models of AML. APVO436 activated patients’ T-cells as evidenced by reduced numbers of circulating CD123+CD34+ and CD33+CD34+ peripheral blasts. Single-agent activity was observed at dose levels ranging from 0.1 mcg/kg to 0.7 mcg/kg in 4 R/R AML patients (50%), including 3 patients with prolonged stable disease (SD) and one patient with complete remission (CR). Likewise, 3 MDS patients had SD (50%) and 3 additional MDS patients (50%) had a marrow CR at dose levels ranging from 0.1 mcg/kg to 0.8 mcg/kg. The median survival for the combined group of 14 R/R AML/MDS patients was 282 days. This early evidence of single-agent activity of APVO436 in R/R AML/MDS patients who failed HMA with or without venetoclax provides proof of concept supporting its in vivo immunomodulatory and anti-leukemic activity and warrants further investigation of its clinical impact potential.

Cancers2区 · 医学

Risk, Characteristics and Biomarkers of Cytokine Release Syndrome in Patients with Relapsed/Refractory AML or MDS Treated with CD3xCD123 Bispecific Antibody APVO436

2区 · 医学

ArticleOA

作者: Lin, Tara L. ; Wang, Eunice ; Mims, Alice S. ; Shami, Paul J. ; Patel, Prapti ; Cogle, Christopher R. ; Lee, Cynthia ; Watts, Justin ; Cull, Elizabeth ; Uckun, Fatih M.

We evaluate the risk, characteristics and biomarkers of treatment-emergent cytokine release syndrome (CRS) in patients with relapsed/refractory acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS) who received APVO436 during the dose-escalation phase of a Phase 1B study (ClinicalTrials.gov, identifier: NCT03647800). Of four patients who developed Grade ≥ 3 CRS, two received steroid prophylaxis. The dose level, gender, race, obesity, or baseline hematologic parameters in peripheral blood did not predict the risk of CRS. Patients with a higher leukemia burden as determined by a higher total WBC, higher percentage of blasts in bone marrow, or higher percentage of blasts in peripheral blood (by hematopathology or immunophenotyping) did not have a higher incidence of CRS. There was an age difference between patients who did versus patients who did not develop CRS (72.9 ± 1.6 years (Median 73.5 years) vs. 63.3 ± 2.3 years (Median: 65.0 years), which was borderline significant (p = 0.04). Premedication with steroids did not eliminate the risk of CRS. Cytokine profiling in patients who developed CRS after APVO436 infusion indicates that the predominant cytokine in this inflammatory cytokine response was IL-6. APVO436-associated CRS was generally manageable with tocilizumab with or without dexamethasone. Notably, the development of CRS after APVO436 therapy did not appear to be associated with a response. The prolonged stabilization of disease, partial remissions and complete remissions were achieved in both patients who experienced CRS, as well as patients who did not experience CRS after APVO436 infusions.

95

项与 Mipletamig 相关的新闻（医药）

2026-09-14

·微信

一线治疗TP53突变癌症，双抗组合疗法临床结果积极；潜在“best-in-class”创新靶点ADC完成首例受试者给药…… | 一周盘点

本期看点： 1. Aptevo Therapeutics公布在研双抗mipletamig联合venetoclax和azacitidine三联疗法在可评估的初治TP53突变急性髓系白血病（AML）患者中取得积极结果。在14例可评估患者中，共有13例（93%）获得临床获益，其中11例（79%）达到完全缓解（CR）或伴不完全血液学恢复的完全缓解（CRi），包括9例完全缓解。 2. BigHat Biosciences旗下潜在“best-in-class”的Cadherin-17（CDH17）靶向新型VHH-Fc抗体偶联药物（ADC）BHB810已在1期临床试验中完成首例患者给药，拟用于治疗胃癌及其他晚期胃肠道（GI）恶性肿瘤。 Mipletamig：公布1b/2期试验结果 Aptevo Therapeutics公布RAINIER临床1b/2期试验最新数据。该公司在研药物mipletamig联合venetoclax和azacitidine三联疗法在可评估的初治TP53突变AML患者中取得积极结果。在14例可评估患者中，包括此前已完成剂量扩展试验中的2例患者，共有13例（93%）获得临床获益，其中11例（79%）达到CR或CRi，包括9例完全缓解。这里所定义的临床获益包括CR、CRi、部分缓解（PR）以及形态学无白血病状态（MLFS）。新闻稿指出，TP53突变AML患者既往治疗效果有限；相比已发表研究中venetoclax联合azacitidine治疗伴高危细胞遗传学特征和TP53突变的初治AML患者所观察到的41%复合缓解率，此次mipletamig三联疗法观察到的CR/CRi率显示出积极信号。 Mipletamig是Aptevo的核心候选药物，是一款CD123/CD3靶向双特异性抗体，旨在通过同时结合白血病细胞和免疫系统T细胞，使两者相互靠近，从而触发对表达CD123的白血病细胞及白血病干细胞的清除。CD123在白血病干细胞和AML原始细胞上呈高表达。该药还采用源自CRIS-7的CD3结合结构域进行设计，旨在降低细胞因子释放综合征发生的可能性及严重程度。目前，RAINIER研究正在一项剂量优化试验中评估mipletamig联合venetoclax和azacitidine用于不适合接受标准高强度化疗的一线AML患者。该阶段研究预计于今年年底完成，公司计划于2027年上半年与监管机构进行沟通，以确定后续开发路径。 BHB810：1期试验首例受试者给药 BigHat Biosciences近日宣布，其靶向CDH17的新型VHH-Fc抗体偶联药物BHB810已在1期临床试验中完成首例受试者给药。BHB810是一款潜在“best-in-class”疗法，拟用于治疗胃癌及其他晚期胃肠道恶性肿瘤。该药物利用BigHat的AI驱动抗体设计平台进行工程化设计，旨在兼顾针对CDH17表达肿瘤的强效抗肿瘤活性、差异化的安全性特征以及良好的可生产性。此次首次人体1期剂量递增试验将评估BHB810的安全性、耐受性、药代动力学及初步抗肿瘤活性，初期将入组晚期胃癌和胃食管结合部（GEJ）肿瘤患者。在覆盖近30种患者来源和细胞来源肿瘤模型的临床前研究中，包括CDH17低表达及异质性表达的胃癌模型，BHB810实现了完全或接近完全的肿瘤清除。根据公司披露，其紧凑型抗体结构以及高稳定性的载荷技术在临床前研究中也展现出良好的安全性特征。随着首例患者完成给药，BHB810正式进入临床开发阶段，后续1期研究将进一步检验其临床安全性、药代动力学特征及初步抗肿瘤活性。 ACE723：IND申请获得FDA许可育世博生物（Acepodia）宣布，其GPC3靶向双载荷抗体偶联药物ACE723的IND申请已获美国FDA许可，该药拟用于治疗不可切除或转移性肝细胞癌（HCC）。ACE723基于Acepodia自主开发的抗体双药物偶联（AD2C）平台构建，该平台整合了抗体工程、药物化学和肿瘤生物学等方面的技术能力。GPC3是一种在HCC中常表达的肿瘤相关抗原，可作为将细胞毒性载荷选择性递送至肿瘤细胞的潜在靶点。计划开展的1期临床研究将评估ACE723在不可切除或转移性HCC患者中的安全性、耐受性、剂量限制性毒性、药代动力学以及初步抗肿瘤活性。其中，剂量递增阶段将重点研究ACE723的安全性特征，并确定后续临床开发及潜在扩展队列所采用的推荐剂量。作为该项目全球开发策略的一部分，Acepodia还于2026年8月向中国国家药品监督管理局（NMPA）提交了ACE723的IND申请。 KT501：IND申请获得FDA许可 Kali Therapeutics宣布，其KT501的IND申请已获美国FDA许可。KT501是一款潜在“first-in-class”的CD19/BCMA/CD3三特异性T细胞衔接器（TCE），拟用于治疗广泛的B细胞介导的自身免疫性疾病。该IgG样三特异性抗体可结合CD19和B细胞成熟抗原（BCMA），从而覆盖包括浆细胞在内的广泛B细胞群体，同时通过公司自主开发的掩蔽设计结合CD3。该设计旨在兼顾药物效力并限制细胞因子释放，以实现更深度的多靶点B细胞清除，同时改善安全性窗口。此次IND获FDA许可得到了KT501正在进行的首次人体1a期临床研究所产生的安全性、耐受性、药代动力学和药效学数据支持。该研究目前正在澳大利亚开展，入组对象为类风湿关节炎（RA）成人患者。随着美国IND许可，KT501将能够进一步推进其临床开发。根据公司此前于2026年3月宣布的全球独家许可协议，KT501已授权给赛诺菲（Sanofi）。 PTT-121：1期试验首例受试者给药炎明生物（Pyrotech Therapeutics）宣布，其新型gasdermin D（GSDMD）抑制剂PTT-121已在1期临床研究中完成首名健康志愿者给药。新闻稿表示，PTT-121是全球首款进入人体临床试验的选择性GSDMD抑制剂，标志着此前被认为“不可成药”的GSDMD靶点迈入临床开发阶段。PTT-121由Pyrotech Therapeutics自主发现和开发，采用静脉给药，最初拟用于治疗感染性休克。该适应症与失调的炎症反应及广泛的细胞焦亡相关。PTT-121此前已于2026年8月4日获得NMPA临床试验许可。这项1期研究为单中心、随机、双盲、安慰剂对照试验，计划招募约84名18～55岁的中国健康成年人，通过单次和多次递增剂量（SAD/MAD）评估静脉给药PTT-121的安全性、耐受性和药代动力学特征。研究主要终点为治疗伴发不良事件（TEAE）发生率，次要终点包括全面的药代动力学和生物标志物评估。与可能对GSDMD产生抑制作用但选择性较低且具有其他分子靶点的再利用药物不同，PTT-121被设计为选择性GSDMD抑制剂。除感染性休克外，公司还计划探索其在更广泛炎症性和自身免疫性疾病中的应用潜力。参考资料： [1] T-MAXIMUM B7-H3-Targeted Allogeneic CAR-T Therapy MT027 Receives FDA Fast Track Designation, Accelerating Global Development for Intracranial Solid Tumors. Retrieved August 31, 2026 from https://www.prnewswire.com/news-releases/t-maximum-b7-h3-targeted-allogeneic-car-t-therapy-mt027-receives-fda-fast-track-designation-accelerating-global-development-for-intracranial-solid-tumors-302862435.html [2] Climb Bio Announces CLYM116 Phase 1 Data Demonstrating Prolonged Half-Life and Best-In-Class APRIL Suppression Supporting Every-12-Week Dosing in IgA Nephropathy. Retrieved September 3, 2026 from https://www.globenewswire.com/news-release/2026/09/03/3355763/0/en/climb-bio-announces-clym116-phase-1-data-demonstrating-prolonged-half-life-and-best-in-class-april-suppression-supporting-every-12-week-dosing-in-iga-nephropathy.html [3] Kali Therapeutics Receives U.S. FDA Clearance for KT501 Investigational New Drug Application. Retrieved September 3, 2026 from https://www.prnewswire.com/news-releases/kali-therapeutics-receives-us-fda-clearance-for-kt501-investigational-new-drug-application-302869142.html [4] ERS 2026 | Mabwell Presents Phase Ib/IIa Clinical Results of Anti-ST2 Monoclonal Antibody 9MW1911 in COPD Patients. Retrieved September 4, 2026 from https://www.prnewswire.com/news-releases/ers-2026--mabwell-presents-phase-ibiia-clinical-results-of-anti-st2-monoclonal-antibody-9mw1911-in-copd-patients-302870024.html [5] Acepodia Announces FDA Clearance of IND Application for ACE723, a Novel Dual-Payload Antibody-Drug Conjugate. Retrieved September 4, 2026 from https://www.prnewswire.com/news-releases/acepodia-announces-fda-clearance-of-ind-application-for-ace723-a-novel-dual-payload-antibody-drug-conjugate-302869787.html [6] Sensorion Announces Approval of Clinical Trial Application in France for SENS-601, Its Investigational Gene Therapy for the Treatment of GJB2-Related Hearing Loss. Retrieved September 4, 2026 from https://www.businesswire.com/news/home/20260902715548/en/Sensorion-Announces-Approval-of-Clinical-Trial-Application-in-France-for-SENS-601-Its-Investigational-Gene-Therapy-for-the-Treatment-of-GJB2-Related-Hearing-Loss [7] Aptevo Reports 93% Clinical Benefit Rate with Mipletamig Triplet in Difficult-to-Treat TP53-Mutated Frontline AML. Retrieved September 4, 2026 from https://aptevotherapeutics.gcs-web.com/news-releases/news-release-details/aptevo-reports-93-clinical-benefit-rate-mipletamig-triplet [8] eGenesis Announces Clinical Update in Ongoing Expanded Access Study of EGEN-2784 in Patients with Kidney Failure. Retrieved September 4, 2026 from https://www.businesswire.com/news/home/20260903759233/en/eGenesis-Announces-Clinical-Update-in-Ongoing-Expanded-Access-Study-of-EGEN-2784-in-Patients-with-Kidney-Failure [9] Pyrotech Therapeutics Doses First Subject in Phase 1 Study of PTT-121, the World’s First Selective GSDMD Inhibitor to Enter Clinical Development. Retrieved September 4, 2026 from https://www.prnewswire.com/news-releases/pyrotech-therapeutics-doses-first-subject-in-phase-1-study-of-ptt-121-the-worlds-first-selective-gsdmd-inhibitor-to-enter-clinical-development-302864784.html [10] BigHat Biosciences Announces First Patient Dosed in Phase 1 Trial Evaluating BHB810, a Novel CDH17-Directed Antibody-Drug Conjugate, for the Treatment of Gastric Cancer and other Advanced Gastrointestinal Tumors. Retrieved September 4, 2026 from https://secure.businesswire.com/news/home/20260901000227/en/BigHat-Biosciences-Announces-First-Patient-Dosed-in-Phase-1-Trial-Evaluating-BHB810-a-Novel-CDH17-Directed-Antibody-Drug-Conjugate-for-the-Treatment-of-Gastric-Cancer-and-other-Advanced-Gastrointestinal-Tumors 免责声明：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：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，传递医学新知

2026-09-07

·今日头条

TP53突变AML缓解率近八成，本周5条管线进展密集披露

刚过去这周，医药行业几条管线动态扎堆冒出来。总部位于西雅图的Aptevo Therapeutics在9月4号放出一组临床数据［1］。入组的是一批携带TP53突变的初治AML患者，三联方案里既有双抗mipletamig，也搭配了venetoclax和azacitidine。 14例可供评估的病例中，有13例对治疗有响应。更关键的是，11例实现了完全缓解级别的应答，其中9例是严格意义上的完全缓解［1］。 TP53突变的AML，历来是血液科医生比较头痛的一类。传统方案能拿到的缓解率数据并不理想。 Aptevo在新闻稿里援引了既有文献的数据作为参照—— venetoclax联合azacitidine的双药方案，在高危细胞遗传学特征合并TP53突变的初治人群里，复合缓解率大约在41%［1］。 mipletamig加入后拉出的79%CR/CRi率，肉眼可见地拉高了基线。当然，眼下这个数字还只是早期信号，完整数据要到今年底才能揭晓［1］。与此同时，BigHat Biosciences的BHB810也完成了首例患者给药［2］。这款ADC药物的靶点是CDH17。在胃癌等消化道肿瘤里，CDH17的表达频率不低。 BHB810用了VHH-FC的抗体结构，加上AI辅助设计。临床前阶段覆盖了大约30种肿瘤模型，即便碰上CDH17表达水平偏低的胃癌模型，也实现了肿瘤完全清除或接近完全清除［2］。公司方面给这个分子的定位是潜在同类最优。 1期研究率先入组的是晚期胃癌和胃食管结合部癌患者［2］。视线转向国内，育世博生物管线里的ACE723拿到了FDA的临床试验许可［3］。这个药瞄准的是GPC3，一个在肝细胞癌中高频出现的肿瘤抗原。技术层面用了双载荷偶联设计［3］。同一天，Kali Therapeutics的KT501也获得了FDA的IND许可［4］。但它的靶向逻辑是CD19和BCMA两个B细胞标志物，加上CD3来衔接T细胞。适应症也拐了个弯，选的是自身免疫病。分子设计上加了掩蔽结构，想在清除B细胞的同时限制细胞因子释放。这款候选药已经在澳大利亚的类风湿关节炎患者中积累了早期人体数据［4］。按2026年3月签的协议，KT501的全球权益已经交给赛诺菲［4］。还有炎明生物的PTT-121，完成了1期首例健康人给药［5］。这是一个GSDMD抑制剂，踩的是细胞焦亡这条通路。行业里把这个分子称为全球首个进入临床的选择性GSDMD靶向药。首攻的适应症是感染性休克，后续还有向炎症和自身免疫领域拓展的空间［5］。回头看这周的管线清单，最抓眼球的数据还是mipletamig那组。在TP53突变AML这种公认难啃的骨头上，翻出将近八成的完全缓解率，确实给行业提了口气。从更长的时间轴来看，这些动作多数还在早期临床阶段，离产业化落地和批量供给还有相当的距离。但管线往前拱一步，后续生产配套的确定性就增加一分。国内biotech在这批进展里占了两个名额，全球多中心布局的意图已经比较明显。早期管线的后续走向，值得行业持续关注。大家觉得今年国内biotech在ADC和双抗这两个赛道上的跟进速度怎么样？欢迎在评论区聊聊。声明：本文仅医药健康行业知识交流，不构成投资、用药指导或生产操作建议。参考文献 [1] Aptevo Therapeutics Inc. Aptevo Reports 93% Clinical Benefit Rate with Mipletamig Triplet in Difficult-to-Treat TP53-Mutated Frontline AML[R]. 2026-09-04 [2] BigHat Biosciences. First Patient Dosed in Phase 1 Trial Evaluating BHB810 for Gastric Cancer and other Advanced Gastrointestinal Tumors[R]. 2026-09-01 [3] Acepodia. FDA Clearance of IND Application for ACE723, a Novel Dual-Payload Antibody-Drug Conjugate[R]. 2026-09-04 [4] Kali Therapeutics. Kali Therapeutics Wins FDA Clearance for KT501 IND[R]. 2026-09-03 [5] Pyrotech Therapeutics. First Subject Dosed in Phase 1 Study of PTT-121, the World's First Selective GSDMD Inhibitor to Enter Clinical Development[R]. 2026-09-04 #医药产业 #药企管线进展 #生物医药

抗体药物偶联物临床申请临床1期

2026-09-06

·药明康德

一线治疗TP53突变癌症，双抗组合疗法临床结果积极；潜在“best-in-class”创新靶点ADC完成首例受试者给药…… | 一周盘点

本期看点： 1. Aptevo Therapeutics公布在研双抗mipletamig联合venetoclax和azacitidine三联疗法在可评估的初治TP53突变急性髓系白血病（AML）患者中取得积极结果。在14例可评估患者中，共有13例（93%）获得临床获益，其中11例（79%）达到完全缓解（CR）或伴不完全血液学恢复的完全缓解（CRi），包括9例完全缓解。 2. BigHat Biosciences旗下潜在“best-in-class”的Cadherin-17（CDH17）靶向新型VHH-Fc抗体偶联药物（ADC）BHB810已在1期临床试验中完成首例患者给药，拟用于治疗胃癌及其他晚期胃肠道（GI）恶性肿瘤。 Mipletamig：公布1b/2期试验结果 Aptevo Therapeutics公布RAINIER临床1b/2期试验最新数据。该公司在研药物mipletamig联合venetoclax和azacitidine三联疗法在可评估的初治TP53突变AML患者中取得积极结果。在14例可评估患者中，包括此前已完成剂量扩展试验中的2例患者，共有13例（93%）获得临床获益，其中11例（79%）达到CR或CRi，包括9例完全缓解。这里所定义的临床获益包括CR、CRi、部分缓解（PR）以及形态学无白血病状态（MLFS）。新闻稿指出，TP53突变AML患者既往治疗效果有限；相比已发表研究中venetoclax联合azacitidine治疗伴高危细胞遗传学特征和TP53突变的初治AML患者所观察到的41%复合缓解率，此次mipletamig三联疗法观察到的CR/CRi率显示出积极信号。 Mipletamig是Aptevo的核心候选药物，是一款CD123/CD3靶向双特异性抗体，旨在通过同时结合白血病细胞和免疫系统T细胞，使两者相互靠近，从而触发对表达CD123的白血病细胞及白血病干细胞的清除。CD123在白血病干细胞和AML原始细胞上呈高表达。该药还采用源自CRIS-7的CD3结合结构域进行设计，旨在降低细胞因子释放综合征发生的可能性及严重程度。目前，RAINIER研究正在一项剂量优化试验中评估mipletamig联合venetoclax和azacitidine用于不适合接受标准高强度化疗的一线AML患者。该阶段研究预计于今年年底完成，公司计划于2027年上半年与监管机构进行沟通，以确定后续开发路径。 BHB810：1期试验首例受试者给药 BigHat Biosciences近日宣布，其靶向CDH17的新型VHH-Fc抗体偶联药物BHB810已在1期临床试验中完成首例受试者给药。BHB810是一款潜在“best-in-class”疗法，拟用于治疗胃癌及其他晚期胃肠道恶性肿瘤。该药物利用BigHat的AI驱动抗体设计平台进行工程化设计，旨在兼顾针对CDH17表达肿瘤的强效抗肿瘤活性、差异化的安全性特征以及良好的可生产性。此次首次人体1期剂量递增试验将评估BHB810的安全性、耐受性、药代动力学及初步抗肿瘤活性，初期将入组晚期胃癌和胃食管结合部（GEJ）肿瘤患者。在覆盖近30种患者来源和细胞来源肿瘤模型的临床前研究中，包括CDH17低表达及异质性表达的胃癌模型，BHB810实现了完全或接近完全的肿瘤清除。根据公司披露，其紧凑型抗体结构以及高稳定性的载荷技术在临床前研究中也展现出良好的安全性特征。随着首例患者完成给药，BHB810正式进入临床开发阶段，后续1期研究将进一步检验其临床安全性、药代动力学特征及初步抗肿瘤活性。 ACE723：IND申请获得FDA许可育世博生物（Acepodia）宣布，其GPC3靶向双载荷抗体偶联药物ACE723的IND申请已获美国FDA许可，该药拟用于治疗不可切除或转移性肝细胞癌（HCC）。ACE723基于Acepodia自主开发的抗体双药物偶联（AD2C）平台构建，该平台整合了抗体工程、药物化学和肿瘤生物学等方面的技术能力。GPC3是一种在HCC中常表达的肿瘤相关抗原，可作为将细胞毒性载荷选择性递送至肿瘤细胞的潜在靶点。计划开展的1期临床研究将评估ACE723在不可切除或转移性HCC患者中的安全性、耐受性、剂量限制性毒性、药代动力学以及初步抗肿瘤活性。其中，剂量递增阶段将重点研究ACE723的安全性特征，并确定后续临床开发及潜在扩展队列所采用的推荐剂量。作为该项目全球开发策略的一部分，Acepodia还于2026年8月向中国国家药品监督管理局（NMPA）提交了ACE723的IND申请。 KT501：IND申请获得FDA许可 Kali Therapeutics宣布，其KT501的IND申请已获美国FDA许可。KT501是一款潜在“first-in-class”的CD19/BCMA/CD3三特异性T细胞衔接器（TCE），拟用于治疗广泛的B细胞介导的自身免疫性疾病。该IgG样三特异性抗体可结合CD19和B细胞成熟抗原（BCMA），从而覆盖包括浆细胞在内的广泛B细胞群体，同时通过公司自主开发的掩蔽设计结合CD3。该设计旨在兼顾药物效力并限制细胞因子释放，以实现更深度的多靶点B细胞清除，同时改善安全性窗口。此次IND获FDA许可得到了KT501正在进行的首次人体1a期临床研究所产生的安全性、耐受性、药代动力学和药效学数据支持。该研究目前正在澳大利亚开展，入组对象为类风湿关节炎（RA）成人患者。随着美国IND许可，KT501将能够进一步推进其临床开发。根据公司此前于2026年3月宣布的全球独家许可协议，KT501已授权给赛诺菲（Sanofi）。 PTT-121：1期试验首例受试者给药炎明生物（Pyrotech Therapeutics）宣布，其新型gasdermin D（GSDMD）抑制剂PTT-121已在1期临床研究中完成首名健康志愿者给药。新闻稿表示，PTT-121是全球首款进入人体临床试验的选择性GSDMD抑制剂，标志着此前被认为“不可成药”的GSDMD靶点迈入临床开发阶段。PTT-121由Pyrotech Therapeutics自主发现和开发，采用静脉给药，最初拟用于治疗感染性休克。该适应症与失调的炎症反应及广泛的细胞焦亡相关。PTT-121此前已于2026年8月4日获得NMPA临床试验许可。这项1期研究为单中心、随机、双盲、安慰剂对照试验，计划招募约84名18～55岁的中国健康成年人，通过单次和多次递增剂量（SAD/MAD）评估静脉给药PTT-121的安全性、耐受性和药代动力学特征。研究主要终点为治疗伴发不良事件（TEAE）发生率，次要终点包括全面的药代动力学和生物标志物评估。与可能对GSDMD产生抑制作用但选择性较低且具有其他分子靶点的再利用药物不同，PTT-121被设计为选择性GSDMD抑制剂。除感染性休克外，公司还计划探索其在更广泛炎症性和自身免疫性疾病中的应用潜力。参考资料： [1] T-MAXIMUM B7-H3-Targeted Allogeneic CAR-T Therapy MT027 Receives FDA Fast Track Designation, Accelerating Global Development for Intracranial Solid Tumors. Retrieved August 31, 2026 from https://www.prnewswire.com/news-releases/t-maximum-b7-h3-targeted-allogeneic-car-t-therapy-mt027-receives-fda-fast-track-designation-accelerating-global-development-for-intracranial-solid-tumors-302862435.html [2] Climb Bio Announces CLYM116 Phase 1 Data Demonstrating Prolonged Half-Life and Best-In-Class APRIL Suppression Supporting Every-12-Week Dosing in IgA Nephropathy. Retrieved September 3, 2026 from https://www.globenewswire.com/news-release/2026/09/03/3355763/0/en/climb-bio-announces-clym116-phase-1-data-demonstrating-prolonged-half-life-and-best-in-class-april-suppression-supporting-every-12-week-dosing-in-iga-nephropathy.html [3] Kali Therapeutics Receives U.S. FDA Clearance for KT501 Investigational New Drug Application. Retrieved September 3, 2026 from https://www.prnewswire.com/news-releases/kali-therapeutics-receives-us-fda-clearance-for-kt501-investigational-new-drug-application-302869142.html [4] ERS 2026 | Mabwell Presents Phase Ib/IIa Clinical Results of Anti-ST2 Monoclonal Antibody 9MW1911 in COPD Patients. Retrieved September 4, 2026 from https://www.prnewswire.com/news-releases/ers-2026--mabwell-presents-phase-ibiia-clinical-results-of-anti-st2-monoclonal-antibody-9mw1911-in-copd-patients-302870024.html [5] Acepodia Announces FDA Clearance of IND Application for ACE723, a Novel Dual-Payload Antibody-Drug Conjugate. Retrieved September 4, 2026 from https://www.prnewswire.com/news-releases/acepodia-announces-fda-clearance-of-ind-application-for-ace723-a-novel-dual-payload-antibody-drug-conjugate-302869787.html [6] Sensorion Announces Approval of Clinical Trial Application in France for SENS-601, Its Investigational Gene Therapy for the Treatment of GJB2-Related Hearing Loss. Retrieved September 4, 2026 from https://www.businesswire.com/news/home/20260902715548/en/Sensorion-Announces-Approval-of-Clinical-Trial-Application-in-France-for-SENS-601-Its-Investigational-Gene-Therapy-for-the-Treatment-of-GJB2-Related-Hearing-Loss [7] Aptevo Reports 93% Clinical Benefit Rate with Mipletamig Triplet in Difficult-to-Treat TP53-Mutated Frontline AML. Retrieved September 4, 2026 from https://aptevotherapeutics.gcs-web.com/news-releases/news-release-details/aptevo-reports-93-clinical-benefit-rate-mipletamig-triplet [8] eGenesis Announces Clinical Update in Ongoing Expanded Access Study of EGEN-2784 in Patients with Kidney Failure. Retrieved September 4, 2026 from https://www.businesswire.com/news/home/20260903759233/en/eGenesis-Announces-Clinical-Update-in-Ongoing-Expanded-Access-Study-of-EGEN-2784-in-Patients-with-Kidney-Failure [9] Pyrotech Therapeutics Doses First Subject in Phase 1 Study of PTT-121, the World’s First Selective GSDMD Inhibitor to Enter Clinical Development. Retrieved September 4, 2026 from https://www.prnewswire.com/news-releases/pyrotech-therapeutics-doses-first-subject-in-phase-1-study-of-ptt-121-the-worlds-first-selective-gsdmd-inhibitor-to-enter-clinical-development-302864784.html [10] BigHat Biosciences Announces First Patient Dosed in Phase 1 Trial Evaluating BHB810, a Novel CDH17-Directed Antibody-Drug Conjugate, for the Treatment of Gastric Cancer and other Advanced Gastrointestinal Tumors. Retrieved September 4, 2026 from https://secure.businesswire.com/news/home/20260901000227/en/BigHat-Biosciences-Announces-First-Patient-Dosed-in-Phase-1-Trial-Evaluating-BHB810-a-Novel-CDH17-Directed-Antibody-Drug-Conjugate-for-the-Treatment-of-Gastric-Cancer-and-other-Advanced-Gastrointestinal-Tumors 免责声明：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：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

临床1期抗体药物偶联物临床结果

100 项与 Mipletamig 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
CD123阳性急性髓性白血病	临床1期	美国	Aptevo Therapeutics, Inc.	2024-10-01
骨髓增生异常综合征	临床1期	美国	Aptevo Research & Development LLC	2018-12-13
难治性急性髓细胞白血病	临床1期	美国	Aptevo Research & Development LLC	2018-12-13

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临床结果

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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


RAINIER (ASH2025)	临床1/2期	急性髓性白血病一线 CD123+	13	Mipletamig/AZA/VEN triplet therapy 9 mcg	繭繭衊憲觸簾製製淵積(壓構構願鹹遞積積艱鑰) = 構簾淵製繭衊觸艱簾鑰製繭窪窪衊鹽鹹淵襯簾 (艱繭齋艱醖鏇餘遞壓襯 ) 更多	积极	2025-12-06
RAINIER (ASH2025)	临床1/2期	急性髓性白血病一线 CD123+	13	Mipletamig/AZA/VEN triplet therapy 18 mcg	繭繭衊憲觸簾製製淵積(壓構構願鹹遞積積艱鑰) = 網構獵膚鹽觸蓋鬱範製製繭窪窪衊鹽鹹淵襯簾 (艱繭齋艱醖鏇餘遞壓襯 ) 更多	积极	2025-12-06
NCT06634394 (RAINIER, Company_Website) 人工标引	临床1/2期	急性髓性白血病	-	Mipletamig + venetoclax + azacitidine	積選齋鏇窪繭鬱壓製鑰(積範觸獵淵繭鏇夢憲網) = 顧衊遞網壓襯壓蓋範積醖遞鹹網顧簾淵鏇淵醖 (蓋壓餘壓獵膚窪餘顧膚 ) 更多	积极	2025-09-16
NCT06634394 (RAINIER, Accesswire) 人工标引	临床1/2期	急性髓性白血病一线	1	Mipletamig	糧窪廠鏇鹹網製獵積獵(廠繭膚餘觸蓋繭鏇構壓) = 襯選構壓簾繭鑰獵鬱壓獵鹹壓獵憲餘鏇鏇鹽糧 (鹽艱範糧鏇獵鹹廠積網 )	积极	2024-11-20
EHA2024	临床1/2期	急性髓性白血病	243	Magrolimab	鏇齋築構壓鏇積餘顧衊(鏇製窪艱選廠顧願繭鑰) = 憲願願鬱壓製糧齋顧蓋鬱淵蓋觸窪繭鑰廠齋艱 (淵襯蓋襯鹹壓廠鏇鏇廠, 0.28 ~ 0.54) 更多	-	2024-05-14
EHA2024	临床1/2期	急性髓性白血病	243	Durvalumab	壓鑰範醖簾淵願衊壓築(廠艱壓繭艱壓廠夢網衊) = 遞鑰製夢簾襯鬱顧簾範獵壓觸鹽鏇憲構願製醖 (網淵願壓衊積製夢鹹築 )	-	2024-05-14
NCT04973618 (Corporate Publications) 人工标引	临床1期	急性髓性白血病一线	11	APVO436+venetoclax+azacitidine	襯遞鏇鏇憲衊夢觸醖壓(鹽餘顧鹹鹹顧鹹襯簾願) = 繭顧鏇鑰選網製醖淵獵觸鑰淵鏇鬱夢鬱壓選顧 (壓網艱襯蓋網衊願膚簾 ) 更多	积极	2023-07-18
NCT03647800 (APVO436-5001, ASH 12022 \| ASH 22022) 人工标引	临床1期	急性髓性白血病 \| 骨髓增生异常综合征	30	APVO436	糧鬱餘鏇窪醖製鹹鏇築(廠鏇築選醖廠壓壓艱醖) = 艱獵遞鏇餘糧淵淵簾憲網顧糧夢鹹構觸齋鑰膚 (壓願鹹衊夢觸淵廠餘衊 ) 更多	积极	2022-11-15
NCT03647800 (APVO436-5001, ASH 12022 \| ASH 22022) 人工标引	临床1期	急性髓性白血病 \| 骨髓增生异常综合征	30	APVO436 (Cohorts 1)	遞獵壓鏇網願鹽鹹壓鏇(鹽壓製夢鬱築鏇糧築觸) = 築廠淵鹹餘鹽憲淵鬱襯鏇構壓憲範餘醖構選艱 (製衊鹽艱衊製壓觸願淵 )	积极	2022-11-15
NCT03647800 (Accesswire) 人工标引	临床1期	急性髓性白血病	11	APVO436	遞鬱顧繭繭壓觸鹽膚蓋(鏇選糧鏇壓選衊壓餘廠) = 繭膚積觸選廠膚網願齋醖艱窪構遞顧窪繭鹹夢 (製鏇觸淵襯糧觸構簾鬱 )	积极	2022-06-09
NCT03647800 (Pubmed \| Cancers (Basel)) 人工标引	临床1期	急性髓性白血病 \| 骨髓增生异常综合征	46	APVO436	獵襯窪構齋廠積鑰鑰簾(艱觸襯積膚鏇蓋廠餘糧) = 廠壓繭糧窪廠鏇積齋範壓憲艱鏇選襯繭襯齋觸 (繭艱築遞網範鏇觸鏇顧 ) 更多	积极	2021-08-15