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）

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. ; Hamilton, Stanley R. ; O’Dwyer, Peter J. ; Kalinsky, Kevin ; Williams, P. Mickey ; Force, Jeremy ; 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

2025-11-01·EClinicalMedicine

Efficacy and safety of systemic therapies following progression on CDK4/6 inhibitors in patients with HR+/HER2− metastatic breast cancer: a systematic review and network meta-analysis

Article

作者: Chiodini, Paolo ; De Angelis, Carmine ; Dieci, Maria Vittoria ; Pagliuca, Martina ; Botticelli, Andrea ; Cataldo, Maria Letizia ; De Laurentiis, Michelino ; Giordano, Antonio ; Vernieri, Claudio ; Criscitiello, Carmen ; Fordellone, Mario ; Mangiacotti, Federica ; Caputo, Roberta ; Malorni, Luca ; Caltavituro, Aldo ; Grieco, Angela ; Longobardi, Alessandra ; Giuliano, Mario ; Gerratana, Lorenzo ; Buonaiuto, Roberto ; Arpino, Grazia ; Lambertini, Matteo

Background:

In the absence of head-to-head trials, optimal treatment sequencing following disease progression on a CDK4/6 inhibitor (CDK4/6i) combined with endocrine therapy (ET) in hormone receptor-positive, HER2-negative (HR+/HER2-) metastatic breast cancer (mBC) remains challenging. To address this gap, we conducted a systematic review and network meta-analysis (NMA) to provide evidence-based guidance for treatment selection in this setting.

Methods:

We identified randomized phase II-III trials involving HR+/HER2- mBC patients whose tumors progressed on CDK4/6i-based therapy, published between January 1, 2014 and June 6, 2025 (PROSPERO n° CRD42024604417). Hazard ratios (HRs) for progression-free survival (PFS) were extracted from published data and analyzed using a frequentist random-effects model. Subgroup analyses were performed based on the duration of CDK4/6i treatment and the presence of ESR1 or PI3K/PTEN/AKT pathway alterations. Treatments were compared with conventional ET or chemotherapy and ranked using the P-score metric. Confidence in network estimates was evaluated using the CINeMA framework. Safety data, including grade ≥3 adverse events (AEs) and treatment discontinuation, were descriptively analyzed.

Findings:

Twenty-eight randomized trials (n = 6544) were included in the NMA. Sapanisertib plus fulvestrant provided the greatest PFS benefit (HR 0.34, 95% CI 0.14-0.82) but had a high discontinuation rate (>15%). Among the approved therapies, ribociclib plus ET (HR 0.57, 95% CI 0.39-0.84), capivasertib plus fulvestrant (HR 0.62, 95% CI 0.51-0.75), and elacestrant (HR 0.70, 95% CI 0.55-0.89) demonstrated superior efficacy. Elacestrant was most effective in patients with ESR1-mutant tumors and among patients with prolonged prior CDK4/6i exposure. Ipatasertib and alpelisib showed the greatest benefits in patients with PI3K/PTEN/AKT alterations. Antibody-drug conjugates (ADCs), such as trastuzumab deruxtecan and sacituzumab govitecan, outperformed standard chemotherapy, albeit with higher toxicity.

Interpretation:

Combinations of targeted agents with ET or novel endocrine agents such as oral selective estrogen receptor degraders (SERDs) demonstrated favorable efficacy and safety profiles in biomarker-selected populations, supporting a shift toward biomarker-driven treatment algorithms. In endocrine-resistant diseases that require chemotherapy, ADCs are the most effective therapeutic option.

Funding:

We acknowledge financial support under the National Recovery and Resilience Plan (NRRP), Mission 4, Component 2, Investment 1.1, Call for tender No. 1409 published on 14.9.2022 by the Italian Ministry of University and Research (MUR), funded by the European Union - NextGenerationEU - Project Title: Identifying predictive/prognostic biomarkers and mechanisms underlying resistance to CDK4/6 inhibition beyond progression in hormone receptor-positive/HER2-negative metastatic breast cancer - CUP E53D23020460001 (Project code: P2022FK2J8, ERC panel: LS7, Principal Investigator: Carmine De Angelis). Grant Assignment Decree No. 1369 adopted on 01.09.2023 by the Italian Ministry of University and Research (MUR).

2025-10-01·Cancer research communications

RAS Pathway Inhibitors Combined with Targeted Agents Are Active in Patient-Derived Spheroids with Oncogenic KRAS Variants from Multiple Cancer Types

Article

作者: Silvers, Thomas ; Fox, Raymond G. ; Davoudi, Zahra ; Teicher, Beverly A. ; Juneja, Poorva ; Morris, Joel ; Coussens, Nathan P. ; Hollingshead, Melinda G. ; Dexheimer, Thomas S. ; Takebe, Naoko ; Kemp, Samantha B. ; Doroshow, James H.

Abstract:

The Kirsten rat sarcoma viral oncogene homolog (KRAS) gene is among the most frequently altered genes in cancer, and the KRAS protein was long deemed undruggable. Recent strategies to target oncogenic KRAS have included both direct inhibition of the KRAS protein and indirect inhibition of its activity by targeting upstream and downstream signaling pathway mediators. A high-throughput screen of multicell-type tumor spheroids was designed to identify active combinations of targeted small molecules and KRAS pathway inhibitors. Inhibitors of the nonreceptor protein tyrosine phosphatase Src homology 2 domain–containing protein tyrosine phosphatase (SHP2) and the guanine nucleotide exchange factor Son of Sevenless homolog 1 (SOS1) were tested to evaluate indirect upstream pathway inhibition, whereas sotorasib directly inhibited the KRAS G12C variant. As single agents, sotorasib and the SHP2 inhibitor batoprotafib (TNO155) exhibited selectivity toward spheroids with KRAS G12C, whereas the SOS1 inhibitor BI-3406 showed varying activity across KRAS variants. Vertical inhibition of the rat sarcoma virus (RAS)/MEK/ERK pathway by targeting SHP2 or SOS1 and the downstream kinases MEK (trametinib) or ERK (temuterkib) was highly effective. Inhibition of upstream tyrosine receptor kinases with nintedanib in combination with batoprotafib or BI-3406 was also effective and, in combination with sotorasib, demonstrated synergy in spheroids harboring KRAS G12C. Dual inhibition of the RAS/MEK/ERK and PI3K/Ak strain transforming (AKT)/mTOR pathways by batoprotafib or sotorasib with either the mTORC1/2 inhibitor sapanisertib or the AKT inhibitor ipatasertib demonstrated combination activity, primarily in spheroids harboring KRAS G12C. The BCL-2 inhibitor venetoclax, in combination with sotorasib, batoprotafib, or BI-3406, resulted in additive and synergistic cytotoxicity. Lastly, concurrent inhibition of the KRAS pathway with sotorasib and batoprotafib demonstrated combination activity in spheroids containing KRAS G12C.

Significance::

KRAS variants are oncogenic drivers for a range of human cancers. Multiple combinations of small-molecule agents that target RAS signaling were screened and reduced the viability of multicell-type tumor spheroids from a variety of human solid tumors. Combinations warranting further testing were identified.

项与 Ipatasertib Dihydrochloride 相关的新闻（医药）

2025-11-17

·bioSeedin柏思荟

齐鲁新“亮剑”

▲点击图片/扫描小程序码查看详情 PREFACE 前言继以最高总计20.45亿元的大手笔将来凯医药旗下AKT抑制剂LAE002收入囊中之后，齐鲁制药还在频频“亮剑”。近日，齐鲁制药自主研发的双抗创新药QLS32015在针对复发或难治性多发性骨髓瘤（RRMM）治疗的III期临床试验，完成首例受试者入组，成为国内首款进入关键注册性III期临床的GPRC5D/CD3双特异性抗体。 2025年美国血液学会（ASH）年会将于当地时间12月6日-12月9日在美国佛罗里达州奥兰多市召开，齐鲁制药将在本次会议上首次公布下一代 GPRC5D/BCMA/CD3 三抗QLS4131在RRMM患者中首次人体试验的初步研究结果。图源：ASH官网作为国内传统制药巨头，齐鲁在创新药领域的战略愈发清晰，不仅要在TCE领域构筑坚实的“护城河”，亦要全方位协同生物药+ADC+小分子药物的抗肿瘤管线，打造治疗闭环。 01 TCE“护城河” 齐鲁制药可以说是在TCE赛道布局最全且推进最快的企业之一。10条管线网络中，7款处在临床试验阶段，2款双抗更率先迈入临床III期，不仅包括双/三/四特异性抗体，覆盖CLDN18.2、GPRC5D、LY6G6D等多个核心靶点，并依托海内外团队的差异化技术平台，形成从成熟靶点到前沿设计的多层次优势。以新近进入III期的QLS32015为例，分子设计上和强生已上市的塔奎妥单抗（GPRC5D/CD3）类似，但1+1非对称结构和亲和力方面的差异，使得前者CD3端亲和力更低（18.1nM），细胞因子释放综合征（CRS）风险降低，安全性更优。 I期试验中，共入组13例RRMM患者，76.9%的患者接受过三重标准治疗（蛋白酶体抑制剂、免疫调节剂、抗CD38单抗），最新临床数据显示，总体客观缓解率（ORR）为76.9%，显著优于传统后线疗法（30-40%），深度缓解率（≥VGPR）38.5%；在RP2D（54μg/kg Q2W）的≥3线且三重暴露人群中，ORR高达90.0%，≥VGPR为80.0%。不到两年时间，QLS32015就迅速闯入III期，并预计入组228例，旨在为国内复发/难治性骨髓瘤患者的后线治疗提供更优选择。另一款备受瞩目的双抗TCE是QLS31905，正在展开一线治疗CLDN18.2阳性晚期胰腺癌的III期临床，在针对多种晚期实体瘤的早期临床中已显示出强大的疾病控制率（DCR）：33例CLDN18.2阳性患者中，胃癌DCR为89.47%，胰腺癌DCR更高达91.67%。作为全球首个进入III期的CLDN18.2/CD3双抗，QLS31905或将给“癌王”乃至实体瘤的治疗带去新变数。以齐鲁的自研平台为基石，美国子公司QLSF Biotherapeutics依托多个技术平台，如TEAD平台（1:1:1的三特异性抗体平台）、TECOS平台（增加CD2共刺激信号）和TECAD平台（TEAD基础上增加CD2共刺激信号的四特异性抗体平台），专注开发差异化前沿产品。 QLSF Biotherapeutics官网目前处在临床前阶段的QL535（PSMA/CD3/CD2）和QL615（MET/EGFR/CD3/CD2）就源于上述平台，代表了齐鲁在TCE赛道的下一步方向。即将于2025 ASH年会上披露数据的QLS4131，同时针对血液肿瘤领域的多发性骨髓瘤（I期剂量递增阶段）和自免领域的系统性红斑狼疮（Ib期临床阶段），这也是TCE适应症的拓展方向。齐鲁的TCE“护城河”显然捕捉到了行业日渐深入的竞争方向：从双抗到三抗/多抗，从血液瘤到实体瘤/自免。 02 协同补充管线围绕来凯医药LAE002展开的高额BD，则是齐鲁依据自身商业化优势，规避早期研发风险，快速填补了AKT抑制剂的空白。不仅能迅速切入以HR+/HER2-乳腺癌为核心的多个癌种，还能与TCE、免疫检查点抑制剂等产品形成“组合拳”，协同发力。自2018年从诺华引入，来凯陆续推进了LAE002针对HR+/HER2-乳腺癌、三阴性乳腺癌、卵巢癌、前列腺癌等适应症的临床试验，作为泛AKT抑制剂，LAE002可同时抑制AKT1/2/3亚型，覆盖更多信号通路和肿瘤人群，疗效稳定持久。在HR+/HER2-乳腺癌领域，LAE002的进度仅次于阿斯利康的Capivasertib。虽然同为泛AKT抑制剂，但LAE002为每日一次的口服制剂，给药更便捷，且更高的安全性使其有望成为潜在BIC（同类最佳）药物。 AKT抑制剂的竞争尚属蓝海，阿斯利康和来凯/齐鲁之外，只有罗氏的Ipatasertib也进入了III期，但在市场潜力最大的乳腺癌（HR+/HER2-）领域，Ipatasertib已经折戟。未来，AKT抑制剂与PARP抑制剂、免疫检查点抑制剂等多种药物的联用是主流趋势，200+仿制药和80+创新药的产品网络，多特异性抗体+小分子靶向药+ADC等药物矩阵，让齐鲁在联用开发方面占据了相当的优势。根据协议，来凯会继续完成HR+/HER2-乳腺癌适应症的III期临床，及后续适应症的开发试验，齐鲁则加速推进LAE002在国内的获批上市，顺利的话，预计2026年递交新药上市申请（NDA）。一方侧重研发，一方侧重商业转化，强强联合，这也是国内biotech与big Pharma深化合作、取长补短的一例典范。 2024年齐鲁研发投入达43.8亿元，TCE领域深耕自主研发、抗肿瘤领域通过BD精准补位，系统性的布局战略使齐鲁得以实现长足发展。注：资料转载自各大公司官网、公开信息源。版权归原作者所有，仅供读者学习、研究或者欣赏，不得用于商业用途，如涉及作品内容、版权和其他问题，请在30日内联系删除；本公众号对转载、分享的内容、陈述、观点判断保持中立，不对所包含内容的真实可靠性或完善性提供任何明示或暗示的保证，仅供读者学习、参考。本文仅为行业分析，不构成投资建议。股市有风险，投资需谨慎。欢迎BD、研发小伙伴添加小助手进交流群（请注明姓名+公司） ▲扫描二维码查看详情 ▲点击图片链接查看详情 ▲点击图片链接查看详情 ↑点击图片长按识别二维码跳转相关链接

临床3期抗体药物偶联物申请上市临床2期临床1期

2025-11-13

·医药经济报

齐鲁20亿砸向抗癌新星！AZ领先，恒瑞、正大天晴紧随，谁主沉浮？

具有泛癌种应用潜力的靶点AKT，正吸引着更多实力强劲的竞争者入局。 11月12日，来凯医药宣布已与齐鲁制药签订独家许可协议，授予后者在中国地区研究、开发和商业化乳腺癌候选新药LAE002 （afuresertib）的独家许可权。据悉，LAE002是一种AKT强效抑制剂，能抑制所有三种AKT亚型（AKT1、AKT2及AKT3），也是全球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。根据协议条款，直至首个适应症在中国获得新药申请批准，来凯医药有权获得最高总计5.3亿元不可退还的首付款和临床开发里程碑付款，以及最高总计20.45亿元的首付款及里程碑款项。此外，来凯医药还有权收取在中国地区内未来净销售额的梯度销售分成。这种将部分研发成果提前变现，并保留产品上市后的长期获益权，已成为当前创新药授权合作的主流模式。今年4月，阿斯利康开发的AKT抑制剂卡匹色替片（Capivasertib）在国内获批上市，这也是国内首个获批上市的AKT抑制剂。在业内看来，齐鲁制药此次重金引进来凯医药AKT抑制剂LAE002，是一笔战略意图明确且颇具前瞻性的交易。这不仅体现了齐鲁制药加码肿瘤创新药管线的决心，也反映出其对AKT抑制剂这一靶点市场潜力的看好。横跨多项难治癌种来凯医药开发的LAE002之所以能达成如此高额的交易，源于产品过硬的价值和广阔的市场前景。世界卫生组织国际癌症研究机构（IARC）数据显示，2022年乳腺癌已成为全球女性的“头号杀手”，每年新增病例约229万例，造成66.6万人死亡。在中国，乳腺癌处于女性癌症发病第2位，其中70%患者属于LAE002聚焦的HR+/HER2-型（激素受体阳性/HER2阴性）。尽管多数HR+/HER2-型乳腺癌患者初始可从一/二线内分泌+CDK4/6抑制剂和/或者化疗中获益，但一段时间后大部分患者可能产生耐药，导致治疗失败，临床亟需耐药后的新型治疗选择。AKT这一靶点的发现，为患者带来了新的希望。 AKT是一种丝氨酸/苏氨酸蛋白激酶，为PI3K/AKT/mTOR信号级联的关键节点。AKT可以激活下游的mTOR蛋白等效应分子，进而刺激肿瘤细胞的代谢生长和增殖、免疫逃逸和血管生成。其中，PTEN可抑制AKT的激活过程，其功能缺失将导致AKT过度激活，引发肿瘤。因此，抑制AKT激活，可望达到治疗泛癌种的效果。来凯医药开发的LAE002是一种AKT强效抑制剂，能抑制所有三种AKT亚型（AKT1、AKT2及AKT3）。目前，LAE002针对HR+/HER2-乳腺癌的Ⅲ期临床试验（AFFIRM-205）招募正按计划进行，将由来凯医药负责完成，拟于2025年第四季度完成受试者入组。此外，来凯医药计划于2026年向CDE提交NDA。不仅如此，来凯医药已在2024年5月宣布LAE002联合全球首款CYP17A1/CYP11B2双靶点抑制剂LAE001治疗转移性去势抵抗性前列腺癌（mCRPC）患者的Ⅲ期临床试验方案获得FDA批准。此外，LAE002联合化疗治疗铂耐药卵巢癌（PROC），联合PD-1抑制剂和化疗治疗PD-（L）1抑制剂耐药实体瘤，以及联合PD-L1抑制剂和化疗治疗三阴性乳腺癌（TNBC）的临床试验均已相继推进。当前，LAE002已在早期临床中展现出更好的安全性，且可以每日给药的便利性，使其具备BIC（同类最优）潜力。除了乳腺癌，LAE002还在前列腺癌等适应症方面显示出开发潜力。这意味着其市场天花板远不止于乳腺癌，未来有望覆盖更多癌种，成为横跨多个大癌种的“重磅炸弹”级产品。这笔交易并非简单的产品引进，其背后是双方在战略上的深度契合。齐鲁制药作为国内传统药企巨头，拥有深度覆盖的商业网络和成熟的市场准入能力。引进处于研发后期的LAE002，能快速填补肿瘤管线中创新靶点药物的空白，实现从“生产驱动”向“创新驱动”的战略延伸。这是一种高风险高回报的策略，规避了从零开始研发的不确定性。作为一家临床阶段的Biotech，来凯医药的商业化能力有限。此次合作不仅让其获得了宝贵的前期现金收入，增强财务状况以支持其他管线研发，还通过销售分成保留了产品上市后的长期获益权。这相当于将部分研发成果提前变现，与齐鲁制药共同承担后续开发和市场推广的风险。这笔交易也为中国医药创新生态提供了范本：Biotech专注前沿研发、大型药企负责商业化推广的优势互补模式正在走向成熟，这种分工协作将有助于加速创新成果转化，提高产品可及性。多方跟进掘金蓝海市场据预测，2029年全球乳腺癌市场总销售额将达到477亿美元，靶向PI3K/AKT/mTOR 的药物占销售额的4%（19.08亿美元）。根据弗若斯特沙利文报告，预计中国乳腺癌市场将会以比全球更高的增速在2030年增长至1223亿元。以4%推算，2030年靶向PI3K/AKT/mTOR的药物销售额将超过48亿元。基于在克服耐药性和治疗特定类型癌症方面展现出的潜力，AKT抑制剂成为当前肿瘤靶向治疗的研发热点。目前，AKT抑制剂在全球范围内仍是一片极具潜力而不拥挤的蓝海，整体竞争格局呈现出“一超一强，多方跟进”的态势。智慧芽新药数据库显示，当前处在临床阶段的AKT抑制剂已超过20款。 2023年11月，阿斯利康的卡匹色替片（Capivasertib）获FDA批准上市，与氟维司群（Fulvestrant）联合使用，用于治疗HR+/HER2-、伴有一种或多种生物标志物改变（PIK3CA、AKT1或PTEN）的局部晚期或转移性乳腺癌成年患者，成为全球首个获批的AKT抑制剂。今年4月，卡匹色替片亦在国内获批上市，并同步申报进入医保目录和商保创新药目录。根据财报，卡匹色替片2024年首个完整销售年的全球销售额为4.3亿美元。今年前三季度，卡匹色替片为阿斯利康贡献了4.95亿美元的营收，同比增长85%，已超过2024年全年销售额。据Clarivate预测，卡匹色替片到2031年将在G7（七国集团）市场获得至少10亿美元的销售额。除了乳腺癌，阿斯利康还在拓展卡匹色替片的其他适应症，包括前列腺癌（Ⅲ期）、非小细胞肺癌（Ⅱ期）和血液肿瘤（I期）等，继续拓宽先发优势。在跨国药企方面，GSK的Afuresertib和辉瑞的ipatasertib进展靠前，已经进入临床Ⅲ期。其中，ipatasertib在罗氏旗下基因泰克与Array BioPharma（已于2019年7月30日被辉瑞收购）的合作中被发现，是一款口服高度特异性在研药物，旨在靶向并结合AKT的所有三种亚型，阻断PI3K/AKT信号通路。而在国内药企方面，恒瑞医药的HRS7415、正大天晴的TQB3912、南京正大天晴的NTQ1062等也已步入临床早期阶段。其中，恒瑞医药的HRS7415自2021年至今已登记3项临床试验申请信息，针对晚期恶性肿瘤；正大天晴的TQB3912则已完成治疗晚期恶性肿瘤的临床试验，正在开展针对HR+/HER2-乳腺癌的Ib/Ⅱ期临床试验。当前，AKT抑制剂最明确的临床价值，在于其作为CDK4/6抑制剂等药物出现耐药情况的后续治疗方案。未来，研发新一代AKT抑制剂，使其具备更好的安全性与更宽的治疗窗口，是明确的研发方向。而将AKT抑制剂与其他作用机制的药物联合使用，是扩大其疗效与应用范围的重要策略。在这场研发竞赛中，谁能够率先取得突破，推出更具优势的AKT抑制剂产品或联合治疗方案，谁就可能占据有利地位。编辑：范晓燕版式编辑：陈淑文审校：马飞、张松京津冀“3+N”联盟启动集采接续，200种中药配方颗粒或价格重构宋瑞霖、张连山、朱义、李佳等畅谈源头创新与国际化突围 GLP-1“三国杀”开局？辉瑞百亿锁定Metsera，诺和诺德中国出招应战 www.yyjjb.com.cn 洞悉行业趋势长按关注医药经济报《中国处方药》学术公众号聚焦药学学术和循证研究长按关注中国处方药《医药经济报》终端公众号记录药品终端产经大事件长按关注21世纪药店

引进/卖出临床3期临床结果放射疗法

2025-11-11

·癌度

《癌度快报》2025年11月11日！

临床试验病友交流群（点击）一、新药快讯 1、前沿抗癌药GFH375联合化疗治疗KRAS基因G12D的胰腺癌开启三期临床！ 2025年 11月11日，药物临床试验登记与信息公示平台官网显示，一项比较GFH375和化疗治疗KRAS基因G12D突变的转移性胰腺癌的三期临床试验启动，这一临床计划入组320名经标准治疗失败的胰腺癌患者，随机分组使用GFH375和研究者选择的化疗。GFH375为一款口服的高活性KRAS基因G12D的靶向药，临床前研究显示该药单药对肿瘤有较好的抑制效果，且显示出低脱靶风险。 2、新型癌症疫苗联合化疗治疗微卫星稳定型肠癌，疾病控制率53.3% 根据发表在《临床肿瘤学杂志-肿瘤学进展》上的一项IB期临床试验，PolyPEPI1018多肽疫苗联合标准化疗TAS-102（替吡嘧啶/三氟尿苷）用于对化疗耐药、微卫星稳定型（MSS）转移性结直肠癌效果显著。中位总生存期达到了8.7个月，中位无进展生存期为4个月，疾病控制率达到了53.3%；无肝转移患者生存更优，中位无进展生存期达到了9.7个月，中位总生存期达到了14.8个月；结直肠癌患者大部分是微卫星稳定型肠癌，疫苗联合治疗能诱导T细胞和抗体的免疫反应，产生让人满意的效果。 3、AKT靶向药联合CYC065联手，有望让40%的前列腺癌患者受益！前列腺癌是男性比较高发的恶性肿瘤，一旦患者对激素治疗耐药则后续缺乏有效的治疗方案。40%的前列腺癌存在PTEN基因缺失或PI3K信号通路激活，英国癌症研究所的科学家设计出了一种药物组合。将CDK9抑制剂Fadraciclib（代号CYC065）联合AKT靶向药Ipatasertib或Capivasertib可有效地诱导前列腺癌细胞死亡。小鼠模型中这一联合用药有效地抑制了肿瘤生长，而对照组的肿瘤在10天内平均增长了6倍，这一药物组合有望让40%的前列腺癌患者受益。二、抗癌前沿 1、《自然》公布防复发癌症疫苗重大进展，接种癌症疫苗全员有效且3年无复发最近，国际著名学术期刊《nature》公布了一项让全球癌症患者都振奋的研究，NeoVax的个性化癌症疫苗让9位高风险肾透明细胞癌患者在平均3年多的术后随访中无一人复发，研究入组了9个人且3年后9人全部无复发，疫苗对每一个患者都是有效的。参与临床试验比较早的2名患者已维持4年未发生复发。这款疫苗主要针对已做过手术、肿瘤完全切除的高复发风险的肾癌。目前胰腺癌、宫颈癌、肝癌、乳腺癌、黑色素瘤术后预防复发的疫苗正在中国开展。 11月份福利癌度联手吉因加，推出“吉爱3000”惠民检项目，最低2000+可及的基因检测专属福利，详情微信扫码联系下方小助手进行免费咨询。咨询全球新药临床试验、报告解读同样可以扫描下面二维码咨询！另外，由于微信公众平台的机制调整，恳请各位粉丝朋友花一两秒钟帮我们点亮文章下方的【小手】和【爱心】，这对我们至关重要。谢谢大家！点亮小手爱心，送来温暖鼓励

疫苗临床结果临床3期临床2期

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	F. Hoffmann-La Roche Ltd.	2020-09-17
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
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

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


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	鬱構餘糧夢憲襯膚選鑰 = 鑰獵築簾鑰願網糧鹽艱獵餘鑰膚觸窪廠願簾繭 (繭製鹽夢鬱選鑰鏇餘窪, 糧糧淵網糧壓鑰繭構積 ~ 蓋網構醖壓獵網廠齋獵) 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	窪鬱衊廠積簾網鹹鑰遞(艱糧願積糧廠獵鑰餘糧) = 淵遞顧構鏇鏇構憲憲夢構顧繭積範艱廠膚網範 (鬱齋憲範獵繭簾鹽願遞, 3.58 ~ 5.62) 更多	积极	2025-05-30
				placebo plus fulvestrant	窪鬱衊廠積簾網鹹鑰遞(艱糧願積糧廠獵鑰餘糧) = 壓淵選選窪憲構簾蓋觸構顧繭積範艱廠膚網範 (鬱齋憲範獵繭簾鹽願遞, 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)	積餘簾衊繭遞醖鏇獵夢 = 窪艱網衊齋鹽壓構遞範餘壓憲餘齋積鏇製餘鏇 (壓觸淵壓顧鹹選鹽夢繭, 餘襯醖鏇淵築夢願網廠 ~ 願膚餘獵鬱網願齋範顧) 更多	-	2024-11-08
				Fulvestrant+Palbociclib+Ipatasertib (Phase Ib: Ipatasertib + Palbociclib +Fulvestrant)	蓋廠鏇觸艱齋簾製觸襯(壓獵夢鑰艱積鬱齋願膚) = 獵鹹選鏇襯觸築膚窪膚窪膚衊膚鹹構鏇衊鬱簾 (夢網製廠齋築觸襯製窪, 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	鬱鹹醖獵餘齋遞憲壓選(鹽廠鏇網簾膚壓鏇鏇蓋) = 網鑰範夢餘遞夢夢鬱廠觸壓範鏇衊艱鏇簾鑰蓋 (鏇餘範憲積襯醖遞鏇鹽 ) 更多	积极	2024-11-05
				Ipatasertib+紫杉醇Ipatasertib+紫杉醇	鬱鹹醖獵餘齋遞憲壓選(鹽廠鏇網簾膚壓鏇鏇蓋) = 築鑰選簾繭鑰範夢憲網觸壓範鏇衊艱鏇簾鑰蓋 (鏇餘範憲積襯醖遞鏇鹽 )
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	遞窪餘鹽顧願糧壓糧窪(構膚淵顧淵蓋憲蓋膚範) = 齋鹽積願網網廠築膚壓鹹糧淵憲簾糧網廠艱遞 (艱繭膚糧願淵鬱廠壓齋, 18.7 ~ 46.3) 更多	积极	2024-05-24
NCT04632992 (MyTACTIC, ASCO2024)	临床2期	晚期恶性实体瘤 ROS1 \| PIK3CA \| ALK ... 更多	252	Entrectinib	窪蓋齋範鏇觸淵膚壓衊(夢鑰窪壓憲壓網衊範淵) = 顧選醖襯醖憲製築網鹽淵壓蓋艱壓構願顧簾鑰 (窪齋繭遞壓構網鬱簾鹽 )	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)	醖糧衊壓繭製窪鹽範簾(鹽襯遞鬱獵鑰積糧蓋願) = 襯齋蓋糧鬱範膚齋鬱壓願築遞鹹積廠遞鹽窪餘 (廠蓋獵鏇鏇淵範遞獵範 ) 更多	积极	2024-05-24
				Ipatasertib (IPA) + Eribulin (E)	醖糧衊壓繭製窪鹽範簾(鹽襯遞鬱獵鑰積糧蓋願) = 鑰鏇衊膚憲遞壓廠觸餘願築遞鹹積廠遞鹽窪餘 (廠蓋獵鏇鏇淵範遞獵範 ) 更多
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	鑰蓋鹽簾積鹽願艱積獵(膚齋齋廠蓋艱糧齋遞積) = 鹽糧網襯鹽餘膚糧鏇願艱艱願鬱製壓遞顧齋鹹 (鹹壓膚繭憲淵獵選憲衊 ) 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)	構憲壓鏇鹽糧網鏇壓鏇(範夢製夢繭鑰醖糧鬱鹽) = 遞選願繭醖範齋艱構淵糧膚製膚衊餘構糧壓壓 (鏇膚選鑰積窪繭選憲積, 積餘鑰鬱觸願構蓋淵範 ~ 積糧鹽選醖淵獵獵窪衊) 更多	-	2024-03-27
				Paclitaxel+Atezolizumab+Ipatasertib (Cohort 2 Arm A: Ipatasertib + Atezolizumab + Paclitaxel)	構憲壓鏇鹽糧網鏇壓鏇(範夢製夢繭鑰醖糧鬱鹽) = 壓願選淵觸壓積衊鑰鏇糧膚製膚衊餘構糧壓壓 (鏇膚選鑰積窪繭選憲積, 醖鬱網壓淵顧齋艱襯膚 ~ 鑰鬱鑰鹹願壓餘蓋築選) 更多
NCT03337724 (IPATunity130, CTgov)	临床3期	HR阳性/HER2阴性乳腺癌	579	Placebo+Paclitaxel (Cohort A: Placebo + Paclitaxel)	襯醖鹹繭蓋艱積簾構壓(廠積憲夢製膚顧遞顧獵) = 蓋觸廠顧鹹艱艱願鏇鹹選選鏇憲夢廠艱遞膚餘 (廠壓製鏇蓋顧鬱遞顧顧, 網淵網網製網膚鑰壓選 ~ 構衊鏇餘製製積壓艱衊) 更多	-	2024-03-12
				Paclitaxel+Ipatasertib (Cohort A: Ipatasertib + Paclitaxel)	襯醖鹹繭蓋艱積簾構壓(廠積憲夢製膚顧遞顧獵) = 獵簾網遞壓膚繭襯鏇築選選鏇憲夢廠艱遞膚餘 (廠壓製鏇蓋顧鬱遞顧顧, 願範觸鹽艱築壓構願構 ~ 繭齋構夢艱構壓觸構夢) 更多