Phase 2 Study of Paclitaxel (NSC #673089) + Ipatasertib (NSC #781451) in Taxane-Refractory Participants With PTEN/AKT-Altered Advanced Non-Breast Solid Tumors: A ComboMATCH Treatment Trial

This phase II ComboMATCH treatment trial tests the usual treatment of chemotherapy (paclitaxel) plus ipatasertib in patients with solid tumor cancers that that cannot be removed by surgery (unresectable), has spread to nearby tissue or lymph nodes (locally advanced) or from where it first started (primary site) to other places in the body (metastatic), and has PTEN and AKT genetic changes. Chemotherapy drugs, such as paclitaxel, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Targeted therapy, such as Ipatasertib, may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. The addition of ipatasertib to paclitaxel in solid tumors with PTEN and AKT genetic changes could increase the percentage of tumors that shrink as well as lengthen the time that the tumors remain stable (without progression). Researchers hope to learn if paclitaxel plus ipatasertib will shrink this type of cancer or stop its growth.

开始日期2023-09-22

申办/合作机构

National Cancer Institute

NCT05332561

/ Recruiting临床2期IIT

Genomics Guided Targeted Post-neoadjuvant Therapy in Patients With Early Breast Cancer - a Multicenter, Open-label, Umbrella Phase-II Study - COGNITION-GUIDE

In early breast cancer (eBC), pathological complete response (pCR) after neoadjuvant therapy acts as surrogate marker for metastasis and overall survival. Therapy intensification by adding an adjuvant therapy line (post-neoadjuvant treatment) substantially lowers the risk of relapse in high-risk breast cancer patients with residual disease after neoadjuvant treatment (non-pCR). While this approach was exemplified in two phase III trials without biomarker-stratification (CREATE-X, KATHERINE), even higher efficiency might be achieved by individualized genomic-guided post-neoadjuvant therapies.
Within the seven-arm umbrella phase-II clinical trial COGNITION-GUIDE, we aim to deliver molecularly-tailored cancer care by implementing an additional response- and genomics-guided post-neoadjuvant therapy after finishing the guideline-compliant post-neoadjuvant treatment in high-risk breast cancer patients with residual cancer burden after neoadjuvant therapy to reduce the substantial risk of local and distant relapse.
The trial evaluates not a single drug but rather a general strategy of precision oncology in the curative setting and provides the basis for future confirmatory biomarker-driven trials.
Allocation to the therapy-arms is conducted by in depth molecular characterization of tumors within the COGNITION registry program.
The study aims to show an overall benefit of the precision medicine approach in high-risk eBC patients and to allow for secondary exploratory evaluation of each study-arm.
The primary endpoint of the study is invasive Disease-Free Survival (IDFS) after 4 years measured from surgery to local or distant relapse or death. The sample size of the entire trial is 240 eligible patients.

开始日期2023-06-29

申办/合作机构

German Cancer Research Center

NCT05862285

/ Recruiting临床3期

An Open-Label, Multicenter Extension Study in Patients Previously Enrolled in a Genentech and/or F. Hoffmann-La Roche Ltd Sponsored Study

The purpose of this extension study is to provide continued treatment with Roche investigational medicinal product (IMP[s]) monotherapy or Roche IMP(s) combined with other agent(s) or comparator agent(s) for eligible participants with cancer who are still on study treatment at the time of roll-over from the parent study and who do not have access to the study treatment locally.

开始日期2023-06-01

申办/合作机构

F. Hoffmann-La Roche Ltd.

100 项与 Ipatasertib Dihydrochloride 相关的临床结果

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100 项与 Ipatasertib Dihydrochloride 相关的转化医学

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100 项与 Ipatasertib Dihydrochloride 相关的专利（医药）

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项与 Ipatasertib Dihydrochloride 相关的文献（医药）

2026-02-04·CLINICAL CANCER RESEARCH

Addition of Ipatasertib to Dual Anti-HER2 Maintenance Therapy in HER2-Positive Metastatic Breast Tumors with PIK3CA Mutations: The Phase Ib SOLTI-1507 IPATHER Trial

Article

作者: Ciruelos, Eva ; Pascual, Tomás ; Saura, Cristina ; Chillara, Samyukta ; Tolosa, Pablo ; Bergamino, Milana ; Oliveira, Mafalda ; Paes Dias, Mariana ; Salvador, Fernando ; Morales, Serafín ; Vega, Estela ; Salvador Bofill, Javier ; Quiroga, Vanesa ; Ferrero-Cafiero, Juan M. ; Servitja, Sonia ; Villacampa, Guillermo ; Gonzalez Farre, Xavier ; Henao, Fernando ; Gavilá, Joaquín ; Cortegoso, Alexandra

Abstract:

Purpose::

The aim of this study was to evaluate the safety and feasibility of ipatasertib combined with trastuzumab and pertuzumab (HP) as maintenance therapy after first-line treatment in patients with HER2-positive metastatic breast cancer harboring PIK3CA mutations (PIK3CAmut).

Patients and Methods::

This prospective, multicenter, single-arm, phase Ib study evaluated the safety and preliminary efficacy of ipatasertib, an AKT inhibitor, combined with HP, with or without endocrine therapy as maintainance therapy, in patients with unresectable locally advanced or metastatic PIK3CAmut, HER2-positive breast cancer following first-line induction chemotherapy and HP.

Results::

Seventeen patients were enrolled, with a median follow-up of 27.7 months. During the dose-selection phase, ipatasertib at 400 mg daily (21 days on and 7 days off) with standard HP was established as the recommended phase II dosage. This decision was based on the absence of dose-limiting toxicities in the first six patients treated at this dosage during the initial 28-day cycle, which constituted the primary endpoint. Grade 3 treatment-related adverse events (TRAE) occurred in seven patients (41.2%), most commonly diarrhea and nausea. Two (11.8%) reported four serious TRAE (diarrhea, vomiting, ischemic stroke, and pneumonitis, one case each) related to ipatasertib, from which they recovered. The confirmed overall response rate was 31.1% [95% confidence interval (CI), 12.1%–58.5%], clinical benefit rate 84.6% (95% CI, 53.7%–97.3%), and median progression-free survival 16.4 months (95% CI, 9.4–NR); 47.3% of patients were progression free at 18 months.

Conclusions::

These results support ipatasertib plus HP as a safe and promising maintenance strategy for HER2-positive breast tumors harboring PIK3CAmut.

2026-02-01·Translational Stroke Research

Transplantation of Skin-Derived Precursor Schwann Cells Ameliorates Secondary Brain Injury after ICH in Mice by Activating the PI3K/AKT/FOXO3a Signaling Pathway

Article

作者: Li, Aihong ; Sun, Qiuwen ; Shen, Jiabing ; Tang, Yuqian ; Sha, Junyi ; Song, Yan ; Xue, Chengbin ; Chen, Yan ; Zhang, Yejing ; Tong, Muyuan

This study investigated the therapeutic potential of skin-derived precursor Schwann cells (SKP-SCs) for secondary brain injury following intracerebral hemorrhage (ICH) and its underlying mechanisms. An ICH model was established in mice via intrastriatal autologous blood injection. SKP-SCs were administered intranasally 24 h post-ICH, with the AKT inhibitor GDC0068 used for intervention. Results demonstrated that transplanted SKP-SCs survived peri-hematomally, significantly improved short- and long-term neurological function, reduced brain tissue damage and neuronal apoptosis, preserved blood-brain barrier integrity, and suppressed microglial/macrophage activation and neutrophil infiltration. Mechanistically, SKP-SCs exerted neuroprotection by activating the PI3K/AKT/FOXO3a signaling pathway. In conclusion, intranasal SKP-SC transplantation alleviates ICH-induced deficits and secondary injury via this pathway, representing a promising therapeutic strategy during the acute phase following ICH.

2025-12-01·CLINICAL CANCER RESEARCH

Ipatasertib in Patients with Tumors with AKT Mutations: Results from the NCI-MATCH ECOG-ACRIN Trial (EAY131) Subprotocol Z1K

Article

作者: Chen, Alice P. ; Harris, Lyndsay N. ; Rubinstein, Larry V. ; Patton, David R. ; McCourt, Carolyn K. ; McShane, Lisa M. ; Kalinsky, Kevin ; O’Dwyer, Peter J. ; Hamilton, Stanley R. ; Force, Jeremy ; Williams, P. Mickey ; Gray, Robert ; Pakanati, Anuradha ; Wei, Zihan ; Conley, Barbara A. ; Tricoli, James V. ; Wang, Victoria ; Arteaga, Carlos ; Flaherty, Keith T.

Abstract:

Purpose::

Activating mutations in AKT genes are rare but play an important role in the commonly dysregulated PI3K/AKT/mTOR signaling pathway in multiple cancers. NCI-MATCH (EAY131) is a tumor-agnostic platform trial that enrolled patients to targeted therapies based on matching tumor genomic alterations. Subprotocol Z1K evaluated ipatasertib, a pan-AKT inhibitor, in patients with AKT1E17K-mutant metastatic tumors.

Patients and Methods::

Patients received ipatasertib 400 mg orally once daily in a 28-day cycle until progression or unacceptable toxicity. Patients with well-controlled diabetes were eligible. Patients with known KRAS, NRAS, HRAS, or BRAF mutations were excluded. Prior PI3K and mTOR inhibitors were allowed. Prior AKT inhibitors were excluded. The primary endpoint was objective response rate (ORR). Secondary endpoints included progression-free survival, 6-month progression-free survival, and toxicity.

Results::

Thirty-five patients were enrolled, and 29 patients were included in the prespecified primary efficacy analysis. Multiple histologies were enrolled, with breast (n = 18) and gynecologic (n = 7) being the most common. The majority had >3 lines of prior therapy (19/29; 65.5%). The ORR was 24.1% (7/29; 90% confidence interval, 11.9%–40.6%) with P < 0.001 against a null rate of 5%. All responses were partial responses. The median response duration was 10.1 months (90% confidence interval, 3.7–10.8). The most common toxicities of any grade included diarrhea (n = 25), nausea (n = 13), and hyperglycemia (n = 9). Grade 3/4 toxicities observed were consistent with reported toxicities for AKT inhibition. Twelve grade 3 events occurred that were thought to be at least possibly related to treatment.

Conclusions::

The study met its primary endpoint with an ORR of 24.1% (P < 0.001), with ipatasertib demonstrating clinically significant activity in heavily pretreated patients with various tumors harboring AKT1E17K mutations.See related commentary by Dahmer Tiecher and Schram, p. 4863

项与 Ipatasertib Dihydrochloride 相关的新闻（医药）

2026-05-07

·药通社

齐鲁超20亿元独家新药，即将报产！

乳腺癌是全球女性中最高发的恶性肿瘤之一。WHO《Breast cancer cases and deaths are projected to rise globally》报告指出，全球乳腺癌的发病与死亡人数呈上升趋势，平均每20名女性中就有1人可能在一生中被确诊。在众多亚型里，HR+/HER2-乳腺癌（激素受体阳性/人表皮生长因子受体2阴性）是绝对的主导亚型，约占患者总数的70%。 2026年4月30日，齐鲁制药官方宣布，近日，由其独家引进中国区域研发与商业化权益的创新靶向药afuresertib（研发代号：LAE002），联合氟维司群治疗HR+/HER2-晚期乳腺癌的重磅Ib/III期临床研究达到主要终点，齐鲁将推进国内上市申请。据公开资料显示，LAE002 （afuresertib）是来凯医药自主开发的一种AKT强效抑制剂，能同时抑制所有三种AKT亚型（AKT1、AKT2及AKT3），也是全球仅有的两种处于晚期临床开发阶段的针对乳腺癌及前列腺癌的AKT抑制剂之一。 AKT是一种丝氨酸/苏氨酸激酶，也是PAM (PI3K/AKT/mTOR) 信号通路的关键节点，对调控细胞生长、增殖、存活及代谢等进程具有核心作用。该通路的失调是乳腺癌（包括HR+、HER2扩增型及三阴性等多种亚型）中常见的致癌事件。因此，靶向AKT成为治疗多种乳腺癌亚型的一个极具吸引力的策略，尤其为克服常规治疗的耐药性提供了新方向。 2025年11月，齐鲁制药与来凯医药达成授权合作，独家引进该药物。根据协议，齐鲁制药全面获得该药在中国境内临床研究、药品开发、生产及商业化全部独家权益，来凯医药则负责完成HR+/HER2-乳腺癌III期临床试验（AFFIRM-205）。作为回报，若LAE002在中国获批首个适应症，来凯医药有权获得5.3亿元不可退还的首付款与总计最高20.45亿元的里程碑款项。此外，来凯医药有权基于中国地区该药物的未来净销售额收取销售分成，分成比率在十余个至二十余个百分点。在Ib期研究中，20例HR+/HER2-乳腺癌接受Afuresertib联合氟维司群治疗后，确认的客观缓解率（cORR）为30%，疾病控制率（DCR）为80%，中位PFS为7.3个月。在11例具有特异性生物标志物改变（PIK3CA/AKT1/PTEN）的患者中，cORR为45.4%，DCR为82%，中位无进展生存期（PFS）为7.3个月。 2026年4月15日，来凯医药正式对外宣布，其旗下在研管线LAE002（afuresertib）联合氟维司群，治疗HR+/HER2-乳腺癌III期临床试验（AFFIRM-205）取得强有力的积极顶线结果，成功达到其主要终点。成为国内首个在该靶点取得III期阳性结果的创新药。全球范围内，AKT抑制剂研发因靶点成药性差、脱靶毒性高，长期被视为创新药研发的“硬骨头”，仅阿斯利康Capivasertib、罗氏Ipatasertib等少数产品进入后期临床。其中Capivasertib已于2023年获FDA批准、2025年登陆中国市场，成为国内首款AKT抑制剂。2024年全球销售额已达4.3亿美元，放量势头强劲。但与此同时，罗氏却因III期数据不佳终止管线研发，这也凸显了该赛道研发的高风险性。在此背景下，齐鲁总计超20亿引进的这款独家新药即将报产，值得期待。参考：北京药研汇 ↓⭐关注药通社，洞见行业趋势↓ 投稿/企业合作/内容沟通：药通社总编—华籍美人（Ww_150525） *添加请注明备注及来意

2026-05-07

·小数的生信笔记

突破！二代AKT降解剂INY-05-040重塑乳腺癌治疗策略 | 多组学解析应激MAPK通路核心机制

在乳腺癌等恶性肿瘤中，PI3K/AKT信号通路的异常激活是驱动肿瘤发生、发展、耐药的核心机制，超50%人类肿瘤存在AKT激酶过度活化。尽管第一代AKT催化抑制剂已进入临床研究，但其仅具细胞抑制作用、无明显细胞毒性、治疗窗窄、易产生耐药等短板，始终难以满足临床需求。靶向蛋白降解（PROTAC）技术的出现，为攻克这一难题带来全新可能。近日，国际顶级期刊Science Signaling发表重磅研究，团队成功开发第二代AKT降解剂INY-05-040，通过多组学联合因果网络分析，系统性解析其作用机制，并挖掘出精准预测疗效的生物标志物，为乳腺癌精准治疗提供全新范式。一、文献研究背景 PI3K/AKT通路的肿瘤核心地位AKT作为丝氨酸/苏氨酸激酶，是PI3K通路的核心下游分子，调控细胞代谢、迁移、增殖与存活；在乳腺癌中，该通路异常激活发生率极高，是理想的治疗靶点。传统AKT抑制剂的临床局限现有ATP竞争性、变构AKT抑制剂多为细胞静止效应，无法彻底清除肿瘤细胞；且存在靶点选择性差、耐药快、治疗窗窄等问题，临床转化受阻。 PROTAC技术的核心优势PROTAC（蛋白降解靶向嵌合体）可利用泛素-蛋白酶体系统彻底降解靶蛋白，相较传统抑制剂具备：降解效率更高、作用更持久、选择性更强、克服耐药等优势。研究核心切入点开发更高效的二代AKT降解剂，结合多组学与计算生物学，解析其特异性作用机制，挖掘可指导临床用药的预测标志物。二、核心研究内容Figure 1｜INY-05-040分子设计与体外/体内功能表征分子设计INY-05-040为双功能降解剂，由AKT催化抑制剂GDC-0068 + VHL E3泛素连接酶配体通过10碳连接链偶联而成；阴性对照INY-05-040-Neg采用无活性VHL配体非对映异构体，排除非特异性效应。体外降解能力快速降解：<5h即可降解全部3种AKT亚型，远快于一代降解剂INY-03-041（12h）；强效抑制下游：显著抑制PRAS40、S6磷酸化，效力远超GDC-0068；长效抑制：洗脱化合物后72h仍持续抑制AKT信号，而催化抑制剂快速反弹。体内药效验证在BT-474C乳腺癌异种移植模型中，INY-05-040可显著降解肿瘤组织AKT，抑制下游信号，效果优于一代降解剂与GDC-0068。Figure 2｜多组学揭示AKT降解的转录与代谢特异性重塑研究采用RNAseq、PRO-seq（新生转录本测序）、LC-MS代谢组，对比降解剂与催化抑制剂的细胞响应差异：转录组层面降解剂处理10h诱导1394个差异基因，远多于GDC-0068（543个），且存在700+特异性调控转录本；两者均抑制细胞周期、糖酵解、mTORC1通路，但降解剂更强激活凋亡、TNFα/NFκB炎症信号。转录因子调控降解剂不抑制SREBP1/2（胆固醇代谢核心转录因子），特异性激活胆固醇稳态相关基因（HMGCR、HMGCS1等）。代谢组层面降解剂诱导最多差异代谢物，甲基丙二酸（MMA）特异性升高，直接抑制胆固醇合成限速酶HMGCR，重塑细胞代谢稳态。Figure 3｜COSMOS整合分析锁定应激MAPK为核心特异性通路团队采用COSMOS因果多组学整合算法，联合转录组+代谢组数据，构建信号调控网络：两种药物均激活ERK1/2（经典代偿通路）；降解剂特异性激活应激MAPK通路：JNK1（MAPK8）、p38α（MAPK14）成为核心调控节点，而GDC-0068几乎不激活该通路； GSEA验证：降解剂显著富集p38依赖的TNFα/NFκB应激信号，进一步证实特异性。Figure 4｜应激MAPK激活验证及与细胞毒性的功能关联信号验证在BT-474、T47D乳腺癌细胞中，INY-05-040可持续激活p38α磷酸化、c-Jun磷酸化/总蛋白升高（JNK激活核心标志），催化抑制剂无此效应。功能关联使用JNK抑制剂JNK-IN-8预处理：可完全逆转T47D细胞的降解剂细胞毒性；对BT-474细胞仅部分逆转，提示降解剂的细胞毒性由应激MAPK+其他通路共同介导。Figure 5｜大规模细胞筛选鉴定JNK基础活性为敏感性标志物广谱抗肿瘤效力在288株肿瘤细胞株中，INY-05-040的生长抑制活性（GI50）显著优于一代降解剂与GDC-0068。乳腺癌精准分层结合DepMap公共多组学数据，对21株乳腺癌细胞分析发现：低基础JNK1磷酸化、c-Jun磷酸化的细胞，对降解剂高度敏感；高基础JNK活性的细胞，表现为耐药；独立验证HCC-1395、HCC-1143（三阴性乳腺癌，高基础JNK活性）对降解剂几乎无响应，完全符合标志物预测。三、实验及分析方法全流程总结本研究构建了“PROTAC药物开发→多组学检测→计算整合→实验验证→标志物挖掘”的完整研发体系，核心流程如下：化合物研发INY-05-040/阴性对照化学合成 → 468种激酶谱筛选选择性 → TMT定量蛋白组验证AKT降解。细胞功能实验乳腺癌细胞（T47D/BT-474/MDA-MB-468等）培养 → 免疫印迹（WB）检测蛋白/磷酸化 → CellTiter Glo检测增殖 → CellTox Green检测细胞毒性。多组学检测RNAseq（稳态转录本）→ PRO-seq（新生转录本）→ LC-MS（极性代谢物）。计算生物学分析PCA降维 → GSEA功能富集 → DoRothEA转录因子活性预测 → COSMOS因果网络整合。体内药效实验BT-474C乳腺癌异种移植模型 → PK/PD检测 → 肿瘤组织WB验证AKT降解。标志物挖掘288株细胞GI50测定 → 结合DepMap转录组/蛋白组/RPPA数据 → 相关性分析锁定JNK活性标志物。四、研究核心结论药物突破成功开发第二代AKT降解剂INY-05-040，实现快速、长效、强效降解全部AKT亚型，抗肿瘤效力显著优于传统催化抑制剂与一代降解剂。机制创新首次揭示AKT降解可特异性激活应激MAPK（JNK/p38）通路，并通过胆固醇代谢重塑、核糖体应激介导细胞毒性，区别于传统催化抑制。精准诊疗鉴定基础JNK低活性是乳腺癌对AKT降解剂敏感的核心生物标志物，可实现患者精准分层，提升治疗获益。范式建立创建“PROTAC+多组学+因果网络”的药物机制解析框架，为靶向降解药物研发提供通用模板。五、研究展望临床转化快速推进INY-05-040临床试验，针对低基础JNK活性的乳腺癌亚组开展精准治疗，拓展至其他AKT异常活化肿瘤。机制深挖进一步解析AKT降解→核糖体应激/胆固醇紊乱→应激MAPK激活的分子调控链，明确核心介导分子。联合策略探索JNK抑制剂与AKT降解剂联合用药，克服高JNK活性耐药，扩大获益人群。技术推广将本研究的多组学整合框架应用于其他PROTAC药物，加速靶向降解药物的机制挖掘与临床转化。文献基础信息 DOI：10.1126/scisignal.adf2670 发表期刊：Science Signaling（2024）发表单位：哈佛医学院贝斯以色列女执事医疗中心、斯坦福大学、海德堡大学、伦敦大学学院、阿斯利康肿瘤研发部等

2026-05-02

·北京药研汇

超20亿元，齐鲁制药“独家引进”1类新药报产在即

乳腺癌是全球女性中最高发的恶性肿瘤之一。WHO《Breast cancer cases and deaths are projected to rise globally》报告指出，全球乳腺癌的发病与死亡人数呈上升趋势，平均每20名女性中就有1人可能在一生中被确诊。在众多亚型里，HR+/HER2-乳腺癌（激素受体阳性/人表皮生长因子受体2阴性）是绝对的主导亚型，约占患者总数的70%。 2026年4月30日，齐鲁制药官方宣布，近日，由其独家引进中国区域研发与商业化权益的创新靶向药afuresertib（研发代号：LAE002），联合氟维司群治疗HR+/HER2-晚期乳腺癌的重磅Ib/III期临床研究达到主要终点，齐鲁将推进国内上市申请。据公开资料显示，LAE002 （afuresertib）是来凯医药自主开发的一种AKT强效抑制剂，能同时抑制所有三种AKT亚型（AKT1、AKT2及AKT3），也是全球仅有的两种处于晚期临床开发阶段的针对乳腺癌及前列腺癌的AKT抑制剂之一。 AKT是一种丝氨酸/苏氨酸激酶，也是PAM (PI3K/AKT/mTOR) 信号通路的关键节点，对调控细胞生长、增殖、存活及代谢等进程具有核心作用。该通路的失调是乳腺癌（包括HR+、HER2扩增型及三阴性等多种亚型）中常见的致癌事件。因此，靶向AKT成为治疗多种乳腺癌亚型的一个极具吸引力的策略，尤其为克服常规治疗的耐药性提供了新方向。 2025年11月，齐鲁制药与来凯医药达成授权合作，独家引进该药物。根据协议，齐鲁制药全面获得该药在中国境内临床研究、药品开发、生产及商业化全部独家权益，来凯医药则负责完成HR+/HER2-乳腺癌III期临床试验（AFFIRM-205）。作为回报，若LAE002在中国获批首个适应症，来凯医药有权获得5.3亿元不可退还的首付款与总计最高20.45亿元的里程碑款项。此外，来凯医药有权基于中国地区该药物的未来净销售额收取销售分成，分成比率在十余个至二十余个百分点。在Ib期研究中，20例HR+/HER2-乳腺癌接受Afuresertib联合氟维司群治疗后，确认的客观缓解率（cORR）为30%，疾病控制率（DCR）为80%，中位PFS为7.3个月。在11例具有特异性生物标志物改变（PIK3CA/AKT1/PTEN）的患者中，cORR为45.4%，DCR为82%，中位无进展生存期（PFS）为7.3个月。 2026年4月15日，来凯医药正式对外宣布，其旗下在研管线LAE002（afuresertib）联合氟维司群，治疗HR+/HER2-乳腺癌III期临床试验（AFFIRM-205）取得强有力的积极顶线结果，成功达到其主要终点。成为国内首个在该靶点取得III期阳性结果的创新药。 AFFIRM-205研究是一项随机、双盲、安慰剂对照临床试验，纳入了261例既往接受内分泌联合或不联合CDK4/6抑制剂治疗后出现疾病进展、伴PIK3CA/AKT1/PTEN改变的局部晚期或转移性HR+/HER2-乳腺癌患者，旨在评估Afuresertib联合氟维司群对比安慰剂联合氟维司群的有效性和安全性。在该研究中，共70.5%的受试者曾接受过CDK4/6抑制剂治疗。结果显示，Afuresertib组和对照组的中位PFS分别为7.6个月和2.0个月（HR=0.33，P<0.0001）。远超对照组的2.0个月，风险比（HR）低至0.33，意味着疾病进展或死亡风险降低67%。安全性方面，每日1次口服Afuresertib，患者耐受性良好，因不良事件而中止治疗的比例极低。整体安全性特征与先前评估该联合疗法的数据一致。基于该III期关键研究的积极结果，齐鲁制药将协同来凯医药于近期向中国国家药品审评中心（CDE）提交afuresertib（LAE002）的新药上市申请（NDA）。 AKT作为PI3K/AKT/mTOR信号通路的核心节点，是肿瘤发生发展及内分泌耐药的关键机制，尤其在约占乳腺癌总数70%的HR+/HER2-亚型中，约40%-50%患者存在该通路异常激活，耐药后治疗选择极为有限，催生了庞大的未满足临床需求。全球范围内，AKT抑制剂研发因靶点成药性差、脱靶毒性高，长期被视为创新药研发的“硬骨头”，仅阿斯利康Capivasertib、罗氏Ipatasertib等少数产品进入后期临床，其中Capivasertib已于2023年获FDA批准、2025年登陆中国市场，成为国内首款AKT抑制剂，2024年全球销售额已达4.3亿美元，放量势头强劲。值得一提的是，罗氏则因III期数据不佳终止管线研发，凸显赛道研发的高风险性。此次afuresertib III期临床研究数据的突破，标志着齐鲁制药这款独家引进创新靶向药距离国内获批更近一步，也将彻底破解HR+/HER2-晚期乳腺癌内分泌耐药治疗难题。希望这款创新靶向药afuresertib早日获批上市，为广大患者提供更多的治疗选择。

100 项与 Ipatasertib Dihydrochloride 相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
-	Ipatasertib Dihydrochloride	-	DB11743

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
ER阳性/HER2阴性乳腺癌	临床3期	澳大利亚	Hoffmann-La Roche, Inc.	2021-01-27
ER阳性/HER2阴性乳腺癌	临床3期	加拿大	Hoffmann-La Roche, Inc.	2021-01-27
ER阳性/HER2阴性乳腺癌	临床3期	新西兰	Hoffmann-La Roche, Inc.	2021-01-27
转移性三阴性乳腺癌	临床3期	中国	罗氏（中国）投资有限公司	2020-09-17
转移性三阴性乳腺癌	临床3期	中国	F. Hoffmann-La Roche Ltd.	2020-09-17
HR阳性/HER2阴性乳腺癌	临床3期	美国	F. Hoffmann-La Roche Ltd.	2018-01-06
HR阳性/HER2阴性乳腺癌	临床3期	美国	罗氏（中国）投资有限公司	2018-01-06
HR阳性/HER2阴性乳腺癌	临床3期	日本	F. Hoffmann-La Roche Ltd.	2018-01-06
HR阳性/HER2阴性乳腺癌	临床3期	日本	罗氏（中国）投资有限公司	2018-01-06
HR阳性/HER2阴性乳腺癌	临床3期	阿根廷	罗氏（中国）投资有限公司	2018-01-06

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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


NCT04650581 (FINER \| CCTG/BCT MA.40/FINER, CTgov)	临床3期	ER阳性/HER2阴性乳腺癌	250	fulvestrant+Ipatasertib	鬱製網積淵窪簾鹹遞鹽 = 鑰鏇廠鬱觸夢獵選艱鹹鹽醖顧醖壓範衊選獵鹹 (構鹽衊範鏇鏇獵壓壓夢, 積鑰網鬱糧築憲壓獵鹹 ~ 築願製鹹淵繭構壓鑰鹽) 更多	-	2026-01-28
NCT06400251 (CTgov)	临床2期	难治恶性实体肿瘤 \| 晚期恶性实体瘤 \| 晚期淋巴瘤 ... 更多	35	Computed Tomography+Ipatasertib	顧簾繭窪夢衊鏇艱積齋 = 憲齋鏇築鑰網顧觸淵積製獵憲選襯衊構衊餘鑰 (選選選鏇壓襯鹹蓋鹽獵, 窪鏇構製齋窪憲餘築艱 ~ 壓網鑰壓獵網網積醖壓) 更多	-	2025-08-26
NCT04650581 (CCTG/BCT MA.40/FINER, ASCO2025) 人工标引	临床3期	乳腺癌二线 ER Positive \| HER2 Negative	250	ipatasertib plus fulvestrant	繭鹹選鏇鬱構鹹選鹽鹽(鏇餘範積簾廠鏇蓋醖糧) = 願艱築蓋淵簾鹹襯廠糧願製餘鏇憲艱襯顧製鏇 (壓蓋憲選網醖窪淵範襯, 3.58 ~ 5.62) 更多	积极	2025-05-30
				placebo plus fulvestrant	繭鹹選鏇鬱構鹹選鹽鹽(鏇餘範積簾廠鏇蓋醖糧) = 積鹹蓋窪餘鹽鏇膚壓憲願製餘鏇憲艱襯顧製鏇 (壓蓋憲選網醖窪淵範襯, 1.84 ~ 3.22) 更多
NCT04060862 (IPATunity150, CTgov)	临床1期	HR阳性/HER2阴性乳腺癌	20	Fulvestrant+Palbociclib+Ipatasertib (Phase 1b: Ipatasertib + Palbociclib +Fulvestrant)	積顧夢壓淵構遞鹹鏇夢 = 範餘糧簾鹹齋糧獵衊窪鹹衊觸衊顧選範糧鏇壓 (糧製餘願憲簾餘範襯網, 構膚淵憲範網製製鬱襯 ~ 築願廠選鏇獵艱觸蓋繭) 更多	-	2024-11-08
				Fulvestrant+Palbociclib+Ipatasertib (Phase Ib: Ipatasertib + Palbociclib +Fulvestrant)	餘廠觸願夢憲鬱襯顧範(獵鏇窪襯壓鹹顧遞願鹽) = 構膚觸艱範夢網鹽鏇簾艱艱鹹蓋顧鏇廠築觸顧 (簾顧遞衊遞蓋夢積觸衊, 52.6) 更多
NCT04931342 (ENGOT-GYN2，GOG-3051，BOUQUET)	临床2期	卵巢上皮癌 \| 复发性铂耐药性卵巢癌末线 \| 二线 \| 三线 HER2阳性，PI3K/AKT/mTOR通路改变	41	恩美曲妥珠单抗	觸繭觸鑰範糧鏇壓淵積(鏇獵簾簾築醖餘選餘醖) = 製膚憲願膚夢憲獵簾壓齋鏇壓選選鏇襯觸鹽網 (觸鑰膚糧夢簾顧鬱繭獵 ) 更多	积极	2024-11-05
				Ipatasertib+紫杉醇Ipatasertib+紫杉醇	觸繭觸鑰範糧鏇壓淵積(鏇獵簾簾築醖餘選餘醖) = 遞遞顧網鑰憲窪襯觸願齋鏇壓選選鏇襯觸鹽網 (觸鑰膚糧夢簾顧鬱繭獵 )
NCT04589845 (TAPISTRY, ASCO2024) 人工标引	临床2期	AKT1突变阳性实体瘤 \| AKT2突变阳性实体瘤 \| AKT3突变阳性实体瘤 AKT2 Mutation \| AKT3 Mutation \| AKT1 Mutation	50	Ipatasertib 400 mg	餘鹹蓋網簾鹹艱壓夢範(繭艱窪膚積憲鹹鑰餘餘) = 鬱鬱遞選憲鑰糧繭構獵壓鏇齋繭餘鑰衊製襯積 (製願窪廠構膚壓鹽醖製, 18.7 ~ 46.3) 更多	积极	2024-05-24
NCT04464174 (PATHFINDER, ASCO2024)	临床2期	晚期三阴性乳腺癌 PI3K/AKT/mTOR pathway	54	Ipatasertib (IPA) + Capecitabine (CA)	窪鹽範鏇願積選簾衊艱(蓋壓顧網齋鑰窪衊觸顧) = 網淵鑰築鬱夢鏇艱壓鬱繭淵齋膚醖蓋鑰願遞廠 (蓋糧廠觸鏇夢網餘夢鬱 ) 更多	积极	2024-05-24
				Ipatasertib (IPA) + Eribulin (E)	窪鹽範鏇願積選簾衊艱(蓋壓顧網齋鑰窪衊觸顧) = 網鏇鏇夢鑰鏇繭艱構選繭淵齋膚醖蓋鑰願遞廠 (蓋糧廠觸鏇夢網餘夢鬱 ) 更多
NCT04632992 (MyTACTIC, ASCO2024)	临床2期	晚期恶性实体瘤 ROS1 \| PIK3CA \| ALK ... 更多	252	Entrectinib	觸夢蓋鏇範夢遞壓醖積(窪壓積鏇襯簾鑰願構構) = 遞鑰構艱鑰齋衊艱鏇糧鹹艱蓋窪壓廠鹽淵鏇網 (襯齋窪選遞齋廠夢鑰壓 )	积极	2024-05-24
NCT04253561 (IPATHER，SOLTI-1507, ESMO_BC2024)	临床1期	HER2阳性乳腺癌维持 \| 巩固 HER2阳性，PIK3CA突变	17	帕妥珠单抗+Ipatasertib+曲妥珠单抗	壓壓鏇艱餘觸夢艱選膚(糧觸蓋繭鑰獵齋鑰鬱選) = 鬱廠鬱壓製鏇憲蓋顧鹽積顧積選糧鬱製範衊夢 (膚淵衊簾選獵夢遞鹽築 ) 更多	积极	2024-05-16
NCT04177108 (IPATunity170, CTgov)	临床3期	三阴性乳腺癌	242	Paclitaxel+Atezolizumab+Ipatasertib (Cohort 1 Arm A: Ipatasertib + Atezolizumab + Paclitaxel)	簾淵夢簾壓鏇鹽夢齋構(願艱窪齋觸鬱製積顧遞) = 網獵願積範醖觸構鹽願鬱鹹獵齋願獵鬱願鏇淵 (範醖膚衊遞製鬱網襯鏇, 積網糧鑰壓淵鏇襯醖衊 ~ 艱鑰憲繭顧選餘顧構選) 更多	-	2024-03-27
				Paclitaxel+Atezolizumab+Ipatasertib (Cohort 2 Arm A: Ipatasertib + Atezolizumab + Paclitaxel)	簾淵夢簾壓鏇鹽夢齋構(願艱窪齋觸鬱製積顧遞) = 築簾願襯範鑰窪鏇願繭鬱鹹獵齋願獵鬱願鏇淵 (範醖膚衊遞製鬱網襯鏇, 遞齋鬱鏇膚願鹽衊衊願 ~ 遞簾艱艱糧襯糧顧鏇選) 更多