Phase 2 Study of 9-ING-41, a Glycogen Synthase Kinase 3 Beta (GSK 3β) Inhibitor, Plus Carboplatin in Patients With Advanced, Metastatic Salivary Gland Carcinoma

9-ING-41 is a small molecule potent selective GSK-3β inhibitor with antitumor activity. This study investigates 9-ING-41 in combination with carboplatin chemotherapy in patients with incurable, recurrent or metastatic salivary gland carcinomas (SGC). Patients with advanced SGC (including all histologic subtypes and adenoid cystic carcinoma [ACC]) will receive 9-ING-41 intravenously (IV) along with carboplatin IV at standard dosing together on Day 1, and 9-ING-41 alone on Day 4 of a 21-day cycle. Participants will be enrolled to two histologic cohorts: Cohort 1 will be comprised of those with ACC, and Cohort 2 will include patients with non-ACC SGC (or all other salivary gland cancer histologies). Treatment will continue until progression of disease, death, or discontinuation of therapy for any reason.

开始日期2030-12-18

申办/合作机构

Actuate Therapeutics, Inc.

NCT06896188

/ Not yet recruiting临床1期IIT

A Phase Ib Study of 9-ING-41 (elraglusib), a Glycogen Synthase Kinase 3-beta (GSK-3β) Inhibitor, Combined with Retifanlimab, a PD-1 Inhibitor, Plus Modified FOLFIRINOX As Frontline Therapy for Patients with Advanced Pancreatic Adenocarcinoma (RiLEY)

This is a study of the combination of 9 ING-41 (elraglusib) and retifanlimab plus mFOLFIRINOX in patients with pancreatic cancer without prior systemic therapy for advanced disease. The safety lead-in cohort will consist of 6 patients, followed by dose de-escalation if necessary, based on safety assessments. After evaluating the safety and tolerability at the initial dose level, the study will proceed to an expansion cohort at the determined safe dose level, with the total maximum enrollment not exceeding 12 patients for the entire study.

开始日期2025-05-31

申办/合作机构

University of Pittsburgh

[+2]

NCT05077800

/ Recruiting临床2期IIT

A Phase II Study of FOLFIRINOX Combined With the Glycogen Synthase Kinase-3 Beta (GSK-3 β) Inhibitor 9-ING-41 and the Transforming Growth Factor-β (TGF-β) Inhibitor Losartan in Patients With Untreated Metastatic Pancreatic Cancer

The purpose of this study is to find out if an experimental drug will prevent metastatic pancreatic adenocarcinoma from becoming resistant to standard treatment for the disease.
The names of the study drugs involved in this study are:
* 9-ING-41
* Losartan
* Ferumoxytol
* FOLFIRINOX (made up of 4 different drugs):
* 5-Fluorouracil (5-FU)
* Oxaliplatin
* Irinotecan
* Leucovorin

开始日期2022-03-21

申办/合作机构

The Massachusetts General Hospital

[+2]

100 项与 Elraglusib 相关的临床结果

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100 项与 Elraglusib 相关的转化医学

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100 项与 Elraglusib 相关的专利（医药）

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项与 Elraglusib 相关的文献（医药）

2025-06-01·ESMO Open

Phase II study of elraglusib (9-ING-41), a GSK-3β inhibitor, in combination with gemcitabine plus nab-paclitaxel in previously untreated metastatic pancreatic cancer

Article

作者: Giles, F J ; Davis, E J ; Weisskittel, T ; Raufi, A G ; Mahalingam, D ; Steeghs, N ; Cervantes, A ; Carneiro, B A ; Huerta, M ; Mulcahy, M ; Mazar, A P ; Berlin, J ; Ugolkov, A ; Powell, S F ; Smith, S ; Mikrut, W ; Sahai, V ; Coveler, A L ; Saeed, A ; Cavalcante, L

INTRODUCTION:

The purpose of this study was to assess the efficacy and safety of elraglusib (9-ING-41), a GSK-3β inhibitor, in combination with gemcitabine/nab-paclitaxel (GnP) in previously untreated metastatic pancreatic ductal adenocarcinoma (mPDAC).

MATERIAL AND METHODS:

In a nonrandomized, Simon's two-stage, phase II study, patients with mPDAC received elraglusib 15 mg/kg on days 1 and 4 each week and GnP on days 1, 8, and 15 in a 28-day cycle. The primary endpoint was disease control rate (DCR); secondary endpoints were objective response rate (ORR), progression-free survival (PFS), overall survival (OS), and treatment-emergent adverse events (TEAEs).

RESULTS:

A total of 42 patients, who were enrolled and treated, had a median age of 67 years and were 57.1% male. Overall, 38 patients received elraglusib at 15 mg/kg and 4 at 9.3 mg/kg with GnP. DCR was 35.7% [95% confidence interval (CI) 21.6% to 52.0%], and ORR was 26.2%. The median PFS and OS were 5.4 months (95% CI 4.4-9.2 months) and 11.9 months (95% CI 7.8-16.5 months), respectively. Most common TEAEs were visual impairment (83.3%), fatigue (69%), and nausea (66.7%). Grade ≥3 TEAEs occurred in 85.7% of patients and included neutropenia (52.4%), leukopenia (42.9%), and fatigue (21.4%). The dose of elraglusib was reduced to 9.3 mg/kg due to increased exacerbation of GnP-related toxicities and frequent dose interruptions and reductions of elraglusib.

CONCLUSIONS:

Elraglusib/GnP showed preliminary clinical activity. In terms of safety, elraglusib resulted in a modest exacerbation of GnP-related toxicities, leading to a dose reduction of elraglusib to 9.3 mg/kg twice a week. Based on the initial efficacy and safety data, the study was amended to a randomized phase II study that will evaluate the 9.3 mg/kg dose.

2024-12-01·European Journal of Haematology

A New Strategy for Adult T‐Cell Leukemia Treatment Targeting Glycogen Synthase Kinase‐3β

Article

作者: Ishikawa, Chie ; Mori, Naoki

ABSTRACT:

Objectives:

The role of glycogen synthase kinase (GSK)‐3β in adult T‐cell leukemia (ATL) caused by human T‐cell leukemia virus type 1 (HTLV‐1) is paradoxical and enigmatic. Here, we investigated the role of GSK‐3β and its potential as a therapeutic target for ATL.

Methods:

Cell proliferation/survival, cell cycle, apoptosis, and reactive oxygen species (ROS) generation were examined using the WST‐8 assay, flow cytometry, and Hoechst 33342 staining, respectively. Expression of GSK‐3β and cell cycle/death‐related proteins, and survival signals was analyzed using RT‐PCR, immunofluorescence staining, and immunoblotting.

Results:

HTLV‐1‐infected T‐cell lines showed nuclear accumulation of GSK‐3β. GSK‐3β knockdown and its inhibition with 9‐ING‐41 and LY2090314 suppressed cell proliferation/survival. 9‐ING‐41 induced G2/M arrest by enhancing the expression of γH2AX, p53, p21, and p27, and suppressing the expression of CDK1, cyclin A/B, and c‐Myc. It induced caspase‐mediated apoptosis by decreasing the expression of Bcl‐xL, Mcl‐1, XIAP, c‐IAP1/2, and survivin, and increasing the expression of Bak and Bax. 9‐ING‐41 also induced ferroptosis and necroptosis, promoted JNK phosphorylation, and suppressed IKKγ and JunB expression. It inhibited the phosphorylation of IκBα, Akt, and STAT3/5, induced ROS production, and reduced glycolysis‐derived lactate levels.

Conclusion:

GSK‐3β functions as an oncogene in ATL and could be a potential therapeutic target.

2024-11-01·Cancer research communications

Elraglusib Induces Cytotoxicity via Direct Microtubule Destabilization Independently of GSK3 Inhibition

Article

作者: Sutherland, Calum ; Tanaka, Tomoyuki U. ; Saurin, Adrian T. ; Li, Shuyu ; Tauro, Sudhir ; Coats, Josh T.

Abstract:

Elraglusib (9-ING-41) is an ATP-competitive inhibitor of glycogen synthase kinase-3 (GSK3) with preclinical studies demonstrating broad activity against many tumor types. Promising early-phase clinical trial data led to FDA orphan drug status, and a randomized phase II study in combination with cytotoxic chemotherapy in pancreatic cancer has recently completed its recruitment. Similarly, single-agent responses in adult T-cell leukemia/lymphoma and melanoma and combination treatment data in several other tumor types have been encouraging. The elraglusib mechanism of action is unknown, but it is unlikely to act through GSK3 inhibition because cytotoxicity is observed below the IC50 for GSK3, and other small molecule GSK3 inhibitors do not produce cytotoxic effects, at least in lymphoma cells. We show here that elraglusib perturbs chromosomal alignment to cause a mitotic arrest in multiple tumor lines. This arrest is caused by direct microtubule (MT) depolymerization, which prevents the attachment of kinetochores to MTs. At clinically relevant doses, these mitotically arrested cells eventually undergo mitotic slippage, leading to gross chromosome missegregation, DNA damage, and apoptosis. These effects explain the cytotoxicity of elraglusib because temporarily pausing cell-cycle progression with the CDK4/6 inhibitor palbociclib abolishes any drug-induced genotoxicity and apoptosis. In summary, elraglusib acts as a direct MT destabilizer both in vitro and across multiple cancer types, resulting in mitotic arrest, DNA damage, and apoptosis. These effects likely account for its broad pan-cancer activity, which does not rely upon GSK3 inhibition as they are not replicated by other GSK3 inhibitors.

Significance::

Elraglusib was designed as a GSK3 inhibitor and is currently in clinical trials for several cancers. We show conclusively that the target of elraglusib that leads to cytotoxicity is MTs and not GSK3. This has significant implications for ongoing clinical trials of the compound and will help in understanding off-target side effects, inform future clinical trial design, and facilitate the development of biomarkers to predict response.

项与 Elraglusib 相关的新闻（医药）

2025-06-03

·BiG生物创新社

2025ASCO研究集锦速报！

2025ASCO如约而至，再次迎来全球肿瘤研究领域的高光时刻，简要整理共飨同仁！本文导读：01 肺癌1.1 SACHI研究：赛沃替尼+奥希替尼对比化疗挑战EGFR-TKI耐药伴Met扩增肺癌成功1.2 HERTHEA-Lung02研究：HER3 ADC治疗TKI耐药EGFR突变NSCLC1.3 OptiTROP-Lung03研究：新款TROP2 ADC挑战TKI和铂类化疗耐药晚期肺癌成绩优异1.4 CAMPASS研究：PDL1单抗联合安罗替尼对比K药一线治疗PDL1阳性肺癌告捷！1.5 SOLO-1研究：sevabertinib BAY2927088治疗HER2突变NSCLC1.6 REZILIENT1研究：Zipalertinib治疗经治EGFR 20ins肺癌，ORR35%1.7 EGFR 20ins和HER2 肺癌药物进展盘点1.8 ALNEO研究：阿来替尼围手术期处理III期ALK阳性NSCLC，MPR42%1.9 InTRist研究：特瑞普利单抗加持大块型III期肺癌同步放化疗成绩斐然1.10 2SMALL研究：卢比替定联合T药二线治疗晚期SCLC，ORR 40.4%。1.11 DeLLphi-303研究：Tarlatamab联合PDL1单抗尝试SCLC维持治疗获初步成绩1.12 CD3/DLL3/DLL3三特异性抗体ZG006三线治疗SCLC，ORR 66.7%，DCR 92.6%1.13 靶向DLL3的BITE药物的进展汇总1.14 KRYSTAL-7研究：adagrasib联合K药治疗KRAS G12C突变肺癌，有效率44%1.15 Checkmate77T研究：O药围手术期治疗疗效更新1.16 EGFR/HER3双抗ADC新药BL-B01D1挑战EGFR非经典突变获佳绩!1.17 C-met ADC Tliso-V/MYTX-011治疗met过表达肺癌1.18 CHRYSALIS研究最终结果：埃万妥单抗治疗MET 14突变肺癌，PFS 5.3月，OS 15.8月。1.19 EGFR-TKI耐药后的处理方向1.20 小细胞肺癌的治疗路线1.21 EGFR突变肺癌的一线考虑（MARIPOSA/FLAURA2）02 乳腺癌2.1 OptiTROP-Breast05研究：新型TROP2 ADC Sac-TMT一线治疗晚期TNBC2.4 FINER研究：AKT抑制剂联合氟维司群二线治疗ER+HER2-乳癌2.5 VERITAC-2研究：首款雌激素受体蛋白降解剂挑战难治HR+HER2-乳癌获突破2.6 SERENA-6研究：雌激素受体降解剂camizestrant联合CDK4/6抑制剂2.7 乳癌内分泌耐药解决新方向：KAT6抑制剂2.8 内分泌+CDK4/6抑制剂进展后的处理总结2.9 HR阳性乳癌整体治疗策略2.10 新的HR+治疗策略2.11 HER2阳性乳癌的治疗策略2.12 CDK4/6抑制剂进军三阳乳癌一线获佳绩2.13 PD1+贝伐+铂治疗三阴乳癌脑转移，颅内有效率77%。2.14 口服紫杉醇对比静脉紫杉醇治疗乳腺癌，疗效不输03 消化道肿瘤3.1 BREAKWATER研究：康菲替尼+西妥昔单抗+mFOLFOX6对比标准治疗3.2 CheckMate 8HW研究：O+Y双免成就MSI-H/dMMR晚期肠癌新一线标准3.3 晚期结直肠癌的一线精准治疗更替3.4 ATOMIC研究：免疫T药+mFOLFOX6辅助治疗dMMR的III期肠癌，DFS提升3.5DESTINY-Gastric04研究：DS8201成功挑战HER2+胃癌二线3.6 Checkmate577研究：O药辅助治疗食管癌，OS有改善趋势3.7LEAP015研究：仑伐替尼+K药+化疗治疗初治晚期胃癌3.8 CodeBreak101研究：索托拉西布+帕尼单抗+FOLFIRI3.9 ANCHOR III期研究：安罗替尼+CapeOx对比贝伐单抗+CapeOx3.10 LOXO-RAS-20001研究：二代KRAS G12C抑制剂联合西妥昔单抗3.11 MATTERHORN研究：免疫Imfinzi（I药）围手术期处理无转移的II-Iva期胃癌，获阳。3.12 1801 Part3B研究：GSK-3β抑制剂联合化疗提升胰腺癌总生存3.13 PANOVA3研究：肿瘤电场疗法联合化疗提升总生存3.14 Claudin18.2 CART治疗晚期胃癌3.15 局晚期直肠癌：放化疗加上PD1单抗，pCR提升（59%：33%）3.16 肠癌治疗策略3.17 胆管癌治疗策略3.18ctDNA对肠癌治疗的预后指导意义3.19 结肠癌腹膜转移：围手术期化疗+细胞减灭术+腹腔热灌注化疗3.20 胃肠肿瘤的CAR-T和TC04 泌尿系统肿瘤4.1 SURE02研究：TROP2 ADC SG联合K药新辅助治疗肾癌，CR率44.4%4.2 肾癌新方向：HIF-2a抑制剂4.3 9MW2821研究：Nectin4 ADC联合PD1一线治疗尿路上皮癌，ORR 80%4.4 TALAPRO-2研究：恩杂鲁胺联合PARP抑制剂在非HRR前列腺癌人群的获益性4.5 膀胱癌的ADC药物疗效对比4.6 放射性配体疗法177LuPSMA联合双免治疗前列腺癌4.7 膀胱癌治疗路线4.8 前列腺癌治疗路线05 ADC5.1 TQB2102：双表位HER2 ADC疗效初现5.2 靶向HER3 ADC新药DB-13105.3 ADC总结06 其他癌肿6.1 SUPRAME研究：靶向PRAME的TCR-T细胞治疗免疫耐药黑色素瘤，ORR56%，可期。6.2 三项头颈鳞癌同步放化疗+免疫的研究对比6.3 NIVOPOSTOP研究：O药联合放化疗辅助治疗头颈鳞癌，DFS提升。6.4 PD-1和VEGF双靶点药物HB0025治疗子宫内膜癌，ORR 80% 01 肺癌 1.1 SACHI研究：赛沃替尼+奥希替尼对比化疗挑战EGFR-TKI耐药伴Met扩增肺癌成功MET扩增是EGFR-TKI耐药的原因之一，为此，MET抑制剂赛沃替尼一直在该领域探索，此次III期SACHI结果公布，对于EGFR突变一线TKI耐药后MET扩增（非T790突变）的晚期非小细胞肺癌患者，接受赛沃替尼+奥希替尼治疗，对比化疗，ORR：58%：34%，PFS 8.2：4.5月（HR 0.34），OS 未成熟，但HR0.84（40%事件数）。其中对于一代二代TKI耐药的患者PFS 9.9：5.4月，对于三代TKI耐药的患者PFS 6.8：3.0月（HR 0.32），脑转移患者亦有获益。1.2 HERTHEA-Lung02研究：HER3 ADC治疗TKI耐药EGFR突变NSCLC2023年12月，HER3 ADC药物Patritumab deruxtecan基于HERTHENA-Lung01结果，获得FDA加速获批，用于TKI和铂类治疗进展的EGFR突变NSCLC，ORR 29.8%，PFS 5.5月，OS 11.9月。此次ASCO公布了HERTHENA-Lung02研究的头对头对比结果，显示，对于既往使用过三代TKI耐药的EGFR突变晚期非鳞NSCLC患者，与铂类化疗相比，PFS 5.8：5.4月（HR 0.77，P=0.011），OS 16.0：15.9月（HR 0.98），无改善。1.3 OptiTROP-Lung03研究：新款TROP2 ADC挑战TKI和铂类化疗耐药晚期肺癌成绩优异Sac-TMT是一款新型TROP2抑制剂，借鉴前辈Patritumab deruxtecan的上市思路，以TKI和铂类化疗耐药的EGFR敏感突变晚期非鳞NSCLC患者为研究对象，与多西他赛进行头对头比较，ORR 45.1%：15.6%，PFS 6.9：2.8月，OS尚未达到，HR 0.49。完胜，且比Patritumab deruxtecan更优，TROP2界的黑马，该药此次在TNBC也有优秀数据披露，见乳癌章节。1.4 CAMPASS研究：PDL1单抗联合安罗替尼对比K药一线治疗PDL1阳性肺癌告捷！K药是目前PDL1≥1%的无驱动基因突变晚期NSCLC的标准治疗，是否会有更高的疗效方案，此次国内专家带来的CAMPASS研究给出了答案，采用PDL1单抗贝莫苏拜单抗联合抗血管小分子药物安罗替尼头对头与K药对比，PFS 11.0:7.1月，HR 0.70，在PDL1≥50%的高表达人群中，PFS 13.3:7.2，HR 0.60，为PDL1阳性NSCLC带来新的一线治疗标准，有望改变肺癌治疗格局。1.5 SOLO-1研究：sevabertinib BAY2927088治疗HER2突变NSCLCSevabertinib是一款HER2抑制剂，一线治疗HER2突变晚期NSCLC，ORR 59.0%，对于经治HER2突变，ORR 60.5%，基于如此优秀的结果，III期SOLO-2研究正在开展。1.6 REZILIENT1研究：Zipalertinib治疗经治EGFR 20ins肺癌，ORR35%对于既往只接受过化疗进展的EGFR20ins，ORR 40%，对于既往使用过埃万妥单抗或其他HER2 TKI药物进展的，ORR24%。1.7 EGFR 20ins和HER2 肺癌药物进展盘点1.8 ALNEO研究：阿来替尼围手术期处理III期ALK阳性NSCLC，MPR42%对于ALK阳性的初治局晚III期NSCLC，采用阿来替尼新辅助治疗2周期，序贯手术治疗+辅助治疗至24周期，主要病理缓解率（MPR）为42%，86% R0切除。III期开展中。1.9 InTRist研究：特瑞普利单抗加持大块型III期肺癌同步放化疗成绩斐然对于突变基因阴性的III期不可切除的NSCLC，同步放化疗+免疫治疗已经成为标准治疗。此次，特瑞普利单抗挑选了III期中大块型（肿瘤≥5cm或淋巴结≥2cm）的NSCLC，在同步放化疗之前增加了2周期的PD1+化疗治疗，对比单纯的化疗，PFS 85.8：54.5月，HR=0.26，ORR：77.8%：40.0%。1.10 2SMALL研究：卢比替定联合T药二线治疗晚期SCLC，ORR 40.4%。既往未接受免疫治疗的受试者ORR44.1%，既往接受过免疫治疗的受试者，ORR 37.3%，总体中位PFS 4.6月，OS 10.1月。1.11 DeLLphi-303研究：Tarlatamab联合PDL1单抗尝试SCLC维持治疗获初步成绩既往基于DeLLphi-301研究，靶向CD3/DLL3的双特异性抗体（BITE）Tarlatamab获批用于经治广泛期SCLC，ORR 40%。此次Tarlatamab公布了DeLLphi-303研究结果，探索一线化免治疗后，采用Tarlatamab联合PDL1作为维持治疗的疗效。DCR64.5%，DCR维持时间7.2个月或更长，初步疗效支撑III期DeLLphi-305研究的开展。1.12 CD3/DLL3/DLL3三特异性抗体ZG006三线治疗SCLC，ORR 66.7%，DCR 92.6%1.13 靶向DLL3的BITE药物的进展汇总1.14 KRYSTAL-7研究：adagrasib联合K药治疗KRAS G12C突变肺癌，有效率44%1.15 Checkmate77T研究：O药围手术期治疗疗效更新既往基于Checkmate77T研究，O药已获批II-IIIB期无EGFR/ALK突变的NSCLC围手术期治疗适应症（O+化疗新辅助4周期+手术+O药辅助至13个周期），此次公布了更新结果，EFS 46.6：16.9月，ctDNA/pCR与EFS相关，OS未达到，但有获益趋势（HR 0.85）。1.16 EGFR/HER3双抗ADC新药BL-B01D1挑战EGFR非经典突变获佳绩!多靶点ADC已成为ADC领域的新发展方向，此次国内一款EGFR/HER3 ADC新药（毒性载荷TOPi）BL-B01D1以肺癌非经典EGFR突变患者为切入点，获得亮眼成绩：治疗EGFR20ins肺癌，ORR 69.2%，中位PFS 10.5个月；治疗HER2突变肺癌，ORR 52.9%，DOR 5.7个月；治疗KRAS/BRAF/MET突变肺癌，ORR40%；整体ORR 46.2%，PFS 5.7个月。为非EGFR经典突变人群带来新的药物方向，尤其在EGFR 20ins领域值得进一步研究。该药在EGFR突变肺癌既往研究获得了63.2%的ORR。1.17 C-met ADC Tliso-V/MYTX-011治疗met过表达肺癌1.18 CHRYSALIS研究最终结果：埃万妥单抗治疗MET 14突变肺癌，PFS 5.3月，OS 15.8月。1.19 EGFR-TKI耐药后的处理方向1.20 小细胞肺癌的治疗路线1.21 EGFR突变肺癌的一线考虑（MARIPOSA/FLAURA2） 02 乳腺癌 2.1 OptiTROP-Breast05研究：新型TROP2 ADC Sac-TMT一线治疗晚期TNBC既往TROP2 ADC Sacituzumab打开了经治三阴乳癌的市场（ORR 35%，PFS 5.6月，OS 12.1月），此次新款TROP2 ADC Sac-TMT在初治三阴乳癌给出亮眼成绩，ORR 70%，PFS 13.4月。2项III期研究正在开展中，有望带来TNBC新的变革。2.2 ASCENT04研究：TROP2 ADC SG联合K药成就PDL1+三阴乳癌新一线标准对于PDL1+（CPS≥10）的三阴乳癌，免疫+化疗是目前标准一线方案，此次ASCO公布的ASCENT04研究，继续升级，采用免疫联合ADC（TROP2）的方案，结果显示，对比化疗联合免疫，PFS 11.2：7.8月，HR 0.65，P<0.001，有望成为新的三阴乳癌一线标准。OS 未成熟，但已见获益趋势（HR 0.89）。2.3 INAVO120研究：PIK3CA抑制剂inavolisib+帕博西利+氟维司群30%-40%的HR+/HER2-乳癌具有PI3K的突变，此次INAVO120研究首次将PI3K抑制剂提到一线，联合CDK4/6抑制剂及氟维司群治疗初治PIK3CA突变的HR+/HER2-乳癌，对比不联合，PFS 17.2：7.3月。催生出了新的靶向导引人群的新一线标准。2.4 FINER研究：AKT抑制剂联合氟维司群二线治疗ER+HER2-乳癌对于既往一线AI+CDK4/6抑制剂耐药的HER+HER2-乳癌患者，采用AKT抑制剂Ipatasertib联合氟维司群治疗，相比单纯的氟维司群，PFS 5，32：19.4月，HR 0.61，P=0.0007。在伴有AKT通路突变的乳癌患者中，获益更大，HR 0.47。2.5 VERITAC-2研究：首款雌激素受体蛋白降解剂挑战难治HR+HER2-乳癌获突破2.6 SERENA-6研究：雌激素受体降解剂camizestrant联合CDK4/6抑制剂另一款口服雌激素受体降解剂camizestrant在ESR1突变后使用，可下降56%的疾病进展风险，PFS 16：9.2个月。2.7 乳癌内分泌耐药解决新方向：KAT6抑制剂表观药物KAT6抑制剂，可以靶向抑制KAT6A/6B，后者在乳癌中的扩增表达率10%-15%，此次KAT6抑制剂联合氟维司群治疗既往CDK4/6抑制剂治疗进展的HR+/HER2-的晚期乳癌，43例患者，ORR 37%，PFS 10.7月。为内分泌耐药乳癌治疗提出新方向。2.8 内分泌+CDK4/6抑制剂进展后的处理总结提出三个方向：①多项新药如艾拉司群获批用于氟维司群无法处理的ESR1突变；②新的PI3K选择性突变抑制剂；③CDK2+CDK4/6；除此上节提及的KAT6抑制剂也是方向之一。2.9 HR阳性乳癌整体治疗策略伴随DS8201在HER2低表达人群获益性的确立及TROP2 ADC的获批，HR+乳癌的后线治疗日益丰富。2.10 新的HR+治疗策略2.11 HER2阳性乳癌的治疗策略2.12 CDK4/6抑制剂进军三阳乳癌一线获佳绩内分泌治疗+CDK4/6抑制剂+赫塞汀一线治疗90例HR+/HER2+晚期乳癌，有效率61%，PFS 30月。为三阳乳癌一线纳入CDK4/6抑制剂拉开序幕。2.13 PD1+贝伐+铂治疗三阴乳癌脑转移，颅内有效率77%。2.14 口服紫杉醇对比静脉紫杉醇治疗乳腺癌，疗效不输 03 消化道肿瘤 3.1 BREAKWATER研究：康菲替尼+西妥昔单抗+mFOLFOX6对比标准治疗BRAF抑制剂康菲替尼+西妥昔单抗+mFOLFOX6对比标准治疗一线治疗BRAF V600E突变的晚期结直肠癌，ORR 65%：37%，PFS 12.8：7.1月，OS：30.3：15.1月。催生了BRAF V600E突变晚期结直肠癌的一线标准治疗。3.2 CheckMate 8HW研究：O+Y双免成就MSI-H/dMMR晚期肠癌新一线标准对于MSI-H/dMMR的晚期结直肠癌，进行O+Y双免对比化疗对比O药单药疗效对比，结果显示，在所有线数O+Y与O药ORR 71%：58%，PFS NR：39.3月，O+Y与化疗PFS 54.1：5.9月。3.3 晚期结直肠癌的一线精准治疗更替随着BRAF突变肠癌一线研究（BREAKWATER）的成功及O+Y双免在MSI-H肠癌一线研究（CheckMate 8HW）的成功，肠癌一线精准治疗局面正在形成。3.4 ATOMIC研究：免疫T药+mFOLFOX6辅助治疗dMMR的III期肠癌，DFS提升3年DFS率86.4%：76.6%，HR0.53.5 DESTINY-Gastric04研究：DS8201成功挑战HER2+胃癌二线对于HER2+胃癌，以曲妥珠单抗为基础的联合治疗是胃癌的一线标准，但是这类人群耐药后，并没有抗HER2的二线方案推荐，雷莫卢单抗联合紫杉醇是目前标准二线，此次DS8201与标准二线进行头对头比较，获得了OS（14.7：11.4月，HR 0.70）、PFS（6.7：5.6月，HR 0.74）及ORR（44.3%：29.1%）的全面优效，为晚期胃癌二线带来新的标准方案。3.6 Checkmate577研究：O药辅助治疗食管癌，OS有改善趋势对于II/III期可切除食管癌，在新辅助放化疗+手术R0切除后，采用O药辅助治疗16周，对比安慰剂，OS提升， 51.7：35.3月，HR 0.85，在CSP≥1的受试者，HR 0.79，鳞癌 HR 0.72。3.7 LEAP015研究：仑伐替尼+K药+化疗治疗初治晚期胃癌3.8 CodeBreak101研究：索托拉西布+帕尼单抗+FOLFIRI采用KRAS抑制剂索托拉西布sotorasib+EGFR单抗帕尼单抗panitumumab+FOLFIRI治疗KRAS G12C突变经治晚期结直肠癌，ORR 58%，DOR 6.6月，OS 15.6月。3.9 ANCHOR III期研究：安罗替尼+CapeOx对比贝伐单抗+CapeOx安罗替尼+CapeOx对比贝伐单抗+CapeOx一线治疗晚期结直肠癌，疗效相近，ORR（均为61%），PFS（7：6.9月）。提供新的用药模式。3.10 LOXO-RAS-20001研究：二代KRAS G12C抑制剂联合西妥昔单抗二代KRAS G12C抑制剂Olomorasib联合西妥昔单抗治疗 KRAS G12C突变肠癌，ORR 43%，DCR 92%，PFS 7.4月。当然市场目前期待如何处理继发耐药问题。3.11 MATTERHORN研究：免疫Imfinzi（I药）围手术期处理无转移的II-Iva期胃癌，获阳。对于无转移的II-Iva期胃癌，采用I药+FLOT新辅助2周期，手术，术后2周期I药+FLOT+I药维持10周期，相比只是淡出FLOT，2年EFS 67%：59%，HR 0.71，2年OS率 76%：70%。3.12 1801 Part3B研究：GSK-3β抑制剂联合化疗提升胰腺癌总生存Elraglusib是一款GSK-3β抑制剂，GSK-3是CD8+T细胞中PD-1基因表达的上游调节因子，并证明GSK-3抑制剂在控制肿瘤生长方面与抗PD-1阻断剂一样有效。本次公布的研究结果显示，Elraglusib联合GnP方案相比单纯GnP，具有OS的提升（10.1：7.2月）。3.13 PANOVA3研究：肿瘤电场疗法联合化疗提升总生存3.14 Claudin18.2 CART治疗晚期胃癌3.15 局晚期直肠癌：放化疗加上PD1单抗，pCR提升（59%：33%）3.16 肠癌治疗策略3.17 胆管癌治疗策略3.18 ctDNA对肠癌治疗的预后指导意义ctDNA被证明是III期可切除肠癌的不良预后因素，但是DYNAMIC-III研究显示，对ctDNA阳性人群进行升级治疗，相比标准治疗，未见RFS的提升（29：36月）。3.19 结肠癌腹膜转移：围手术期化疗+细胞减灭术+腹腔热灌注化疗腹膜转移在结肠癌患者中常见，相比单纯手术，手术围手术期进行化疗+细胞减灭术+腹腔热灌注化疗，PFS翻倍（14：7月），但OS获益趋势小（44：39月）。3.20 胃肠肿瘤的CAR-T和TC 04 泌尿系统肿瘤 4.1 SURE02研究：TROP2 ADC SG联合K药新辅助治疗肾癌，CR率44.4%4.2 肾癌新方向：HIF-2a抑制剂4.3 9MW2821研究：Nectin4 ADC联合PD1一线治疗尿路上皮癌，ORR 80%4.4 TALAPRO-2研究：恩杂鲁胺联合PARP抑制剂在非HRR前列腺癌人群的获益性4.5 膀胱癌的ADC药物疗效对比4.6 放射性配体疗法177LuPSMA联合双免治疗前列腺癌对比单纯177LuPSMA，pPFS HR 0.53。4.7 膀胱癌治疗路线4.8 前列腺癌治疗路线 05 ADC 5.1 TQB2102：双表位HER2 ADC疗效初现TQB2102是一款双表位HER2 （曲妥+帕妥）ADC（毒性载荷TOPi，DAR=6），治疗实体瘤，在HER2阳性乳癌，ORR 52%；在HER2低表达乳癌，ORR 47%；在HER2 3+肠癌，ORR 44%；在HER2阳性胃癌/胃食管结合部癌，ORR 40%。疗效均可看，值得关注。5.2 靶向HER3 ADC新药DB-1310DB-1310，一款靶向HER3的ADC药物（毒性载荷TOPi，DAR=8）治疗123例晚期实体瘤，ORR为31%，中位PFS 5.5个月；其中46例EGFR突变肺癌患者，ORR 44%。安全性良好。5.3 ADC总结部分会场对ADC的发展进行了讨论，看到了一些振奋的疗效例如HER3 ADC DB-1310，一些新的ADC正在探索中，提出未来ADC的发展方向：新的靶点、更强的结合力、新的毒素载荷、更强的入脑性。以HER3靶点药物目前的不俗表现，HER3靶点成为另一个“HER2“吗？新三款ADC安全性比较。 06 其他癌肿 6.1 SUPRAME研究：靶向PRAME的TCR-T细胞治疗免疫耐药黑色素瘤，ORR56%，可期。6.2 三项头颈鳞癌同步放化疗+免疫的研究对比6.3 NIVOPOSTOP研究：O药联合放化疗辅助治疗头颈鳞癌，DFS提升。6.4 PD-1和VEGF双靶点药物HB0025治疗子宫内膜癌，ORR 80%共建Biomedical创新生态圈！如何加入BiG会员？

ASCO会议抗体药物偶联物临床结果临床3期

2025-06-02

·FierceBiotech

ASCO: Actuate\'s pancreatic cancer drug boosts survival by 3 months in phase 2 study

Adverse events were similar between the two cohorts, said Actuate Therapeutics. \n Actuate Therapeutics has set its sights on getting elraglusib approved for pancreatic cancer after the glycogen synthase kinase‐3 beta (GSK-3β) drug showed a three-month survival increase in a phase 2 study.The Texas- and Ireland-based biotech evaluated the therapy in a trial of 286 patients with metastatic pancreatic ductal adenocarcinoma (mPDAC) who received either elraglusib and chemotherapy or chemotherapy alone. The elraglusib patients saw a median overall survival of 10.1 months, compared to 7.2 months for the comparator cohort, hitting the study’s primary endpoint, according to a May 31 release.The data, which Actuate unveiled at the American Society of Clinical Oncology (ASCO) annual meeting in Chicago over the weekend, also showed that the 12-month survival rate for elraglusib patients was 44.1%—double the 22.3% rate for those on chemotherapy only.Overall response rates were 29% and 21.8%, respectively, for the two groups, while there was also a slight improvement in median progression-free survival at 5.6 months compared to 5.1 months.Adverse events were similar between the two cohorts, said Actuate. Most treatment-related adverse events were grades 1-2, with two-thirds of patients experiencing transient visual impairments that were reversible.While cases of neutropenia—low levels of a type of white blood cell—reached grade 3 “or higher,” the rates of these events or sepsis were similar across both arms of the study, the biotech stressed.“Combined with a manageable safety profile and strong emerging mechanistic insights, these results reinforce the transformative potential of our GSK-3β inhibitor program,” Actuate CEO Daniel Schmitt said in the release. “Based on the clear clinical benefit and well-tolerated safety profile, we intend to engage with the FDA and EMA in the second half of this year to align on a path to registration,” Schmitt added. “We believe this enables us to move rapidly towards commercialization and delivery of this first-in-class therapy to patients with an urgent unmet need.”Actuate went public last summer via a scaled-back $22.4 million IPO. The company’s stock hovered around its $8 debut price until good news about elraglusib’s prospects in recent months saw the shares reach a closing price on Friday of $11.90. The stock has since risen up to $13.74 in premarket trading Monday.Pancreatic cancer is a notoriously tough indication to treat that has seen few advances. Elraglusib is designed to bind to GSK-3β, disrupting cancer pathways associated with the invasion of tumor cells and resistance to chemotherapeutic agents and radiation. Preclinical tests suggested the intravenous small molecule could have an impact on diseases like urothelial cancer and renal cell carcinoma, leading Actuate to take the candidate into human studies in 2018.

$ASCO: Actuate\'s pancreatic cancer drug boosts survival by 3 months in phase 2 study$

临床结果ASCO会议临床2期IPO

2025-06-02

·Firstwordpharma

ASCO25: Actuate flexes survival benefit of front-line elraglusib in mid-stage pancreatic cancer study

Actuate Therapeutics reported positive top-line findings from a Phase II trial of the glycogen synthase kinase 3 beta (GSK-3β) inhibitor elraglusib in combination with chemotherapy, demonstrating a clinically meaningful survival benefit in previously untreated patients with metastatic pancreatic ductal adenocarcinoma (PDAC). The data were presented at the American Society of Clinical Oncology (ASCO) annual meeting on Saturday.The Actuate-1801 Part 3B study evaluated elraglusib plus gemcitabine/nab-paclitaxel (GnP) against GnP alone as first-line treatment in 286 patients with metastatic PDAC. The primary endpoint was median overall survival (OS), assessed with one-year survival estimates.Results showed that elraglusib plus GnP met the main goal, showing a median OS of 10.1 months versus 7.2 months for GnP alone, translating to a 37% reduction in risk of death. Twelve-month survival rates nearly doubled from 22.3% for GnP alone to 44.1% for elraglusib plus GnP, with extended survival benefits persisting at 18 and 24 months.On secondary endpoints, elraglusib plus GnP demonstrated numerical improvements over chemotherapy alone in overall response rates (29.0% vs 21.8%), median duration of response (5.5 months vs 4.0 months) and median progression-free survival (5.6 months vs 5.1 months). Moreover, exploratory biomarker analysis revealed promising immune modulation patterns.The elraglusib-GnP combination showed a comparable safety profile to GnP alone in terms of treatment-emergent adverse events (TEAEs) and serious AEs. Most TEAEs were Grade 1-2, with transient, reversible visual impairments reported in about two-thirds of patients. While Grade 3+ neutropenia was reported, rates of febrile neutropenia and sepsis were similar across both arms.“Combined with a manageable safety profile and strong emerging mechanistic insights, these results reinforce the transformative potential of our GSK-3β inhibitor programme," said Daniel Schmitt, chief executive of Actuate. The company plans to engage with the US and EU regulators in the second half of the year to establish a pathway towards product registration.

临床结果ASCO会议临床2期

100 项与 Elraglusib 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
转移性黑色素瘤	临床2期	美国	Actuate Therapeutics, Inc.	2023-05-31
转移性黑色素瘤	临床2期	美国	Lantern Pharma, Inc.	2023-05-31
转移性胰腺癌	临床2期	美国	Actuate Therapeutics, Inc.	2022-03-21
转移性胰腺腺癌	临床2期	美国	Actuate Therapeutics, Inc.	2022-03-21
转移性骨肉瘤	临床2期	美国	Actuate Therapeutics, Inc.	2022-03-01
小细胞肉瘤	临床2期	美国	Actuate Therapeutics, Inc.	2022-03-01
晚期胰腺腺癌	临床2期	美国	Actuate Therapeutics, Inc.	2022-01-26
晚期胰腺腺癌	临床2期	美国	Incyte Corp.	2022-01-26
胰腺导管腺癌	临床2期	美国	Incyte Corp.	2022-01-26
胰腺导管腺癌	临床2期	美国	Actuate Therapeutics, Inc.	2022-01-26

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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


NCT03678883 (1801 part 3B, ASCO2025)	临床2期	转移性胰腺导管腺癌 CA 19-9 levels \| IFNβ \| PD-L1	-	Elraglusib 9.3 mg/kg IV once weekly + Gemcitabine/nab-paclitaxel	遞餘憲衊鹹觸願構構選(夢夢蓋積範鑰廠膚夢廠) = 蓋繭簾選襯廠憲繭壓製蓋製窪艱鬱簾壓顧構廠 (製餘繭網鬱築積夢繭遞 ) 更多	积极	2025-05-30
				Gemcitabine/nab-paclitaxel	遞餘憲衊鹹觸願構構選(夢夢蓋積範鑰廠膚夢廠) = 膚餘築鬱選廠憲窪壓遞蓋製窪艱鬱簾壓顧構廠 (製餘繭網鬱築積夢繭遞 ) 更多
NCT03678883 (Actuate-1801 Part 3B, GlobeNewswire) 人工标引	临床2期	转移性胰腺癌一线	-	elraglusib + gemcitabine/nab-paclitaxel (GnP)	窪構夢齋壓構蓋蓋製廠(顧願顧觸簾繭齋蓋遞艱) = elraglusib in combination with gemcitabine/nab-paclitaxel (GnP) met the primary endpoints and achieved statistical significance in topline results. 糧淵艱獵繭製鏇鑰餘築 (艱廠獵餘範構鹹鑰網蓋 ) 达到	积极	2025-05-09
				gemcitabine/nab-paclitaxel (GnP)
NCT05010629 (AACR2025)	临床2期	唾液腺肿瘤 tumor PD-L1 \| GSK-3β expression	32	Elraglusib	艱顧製繭淵壓醖觸壓鬱(鑰構製襯廠醖鏇蓋蓋鑰) = 獵觸齋網衊鏇糧願鏇範衊遞餘鏇蓋蓋鑰鹽鹹糧 (淵餘鬱夢簾範積醖廠製, 2 ~ 25) 更多	积极	2025-04-29
NCT04239092 (Actuate-1801, GlobeNewswire) 人工标引	临床2期	胰腺癌一线	286	Elraglusib + gemcitabine/nab-paclitaxel	壓蓋構鹹製願壓鹽鬱醖(築範蓋獵觸積鹽廠窪選) = 願選膚遞壓鑰艱艱蓋夢餘醖鑰網鹹網範顧糧糧 (製鏇鬱齋糧繭鏇憲製範 ) 达到更多	积极	2024-12-17
				gemcitabine/nab-paclitaxel	壓蓋構鹹製願壓鹽鬱醖(築範蓋獵觸積鹽廠窪選) = 壓鹹範鏇襯壓淵衊糧觸餘醖鑰網鹹網範顧糧糧 (製鏇鬱齋糧繭鏇憲製範 ) 达到更多
NCT04239092 (GlobeNewswire) 人工标引	临床1/2期	尤文肉瘤 \| 促纤维增生性小圆细胞瘤	8	elraglusib	夢憲醖襯餘齋願遞蓋壓(鹽願鬱糧簾鏇醖遞選壓) = 網範製淵構餘顧鏇鬱範積願艱製艱蓋顧觸築鬱 (製窪鏇廠餘積蓋鏇壓膚 ) 更多	积极	2024-09-09
NCT03678883 (ASCO 12023 \| ASCO 22023) 人工标引	临床2期	晚期胰腺导管腺癌	42	gemcitabine+Albumin-Bound Paclitaxel+Elraglusib	齋膚遞選繭積築糧窪襯(蓋觸築廠簾窪選鏇夢網) = 構願糧淵鹽膚顧糧膚築築齋鑰廠廠顧範憲觸鏇 (鏇廠鑰繭衊艱簾網襯範, 32.5 ~ 70.6) 更多	积极	2023-05-26
NCT03678883 (AACR2023) 人工标引	临床1/2期	晚期癌症三线	-	elraglusib (melanoma)	簾製觸製獵顧鹹鑰築廠(積繭顧衊窪醖憲壓襯糧) = 製構觸夢鏇獵繭獵構壓餘製壓壓壓壓製構鑰夢 (簾淵壓積範鬱願觸製蓋 )	积极	2023-04-14
				elraglusib (colorectal cancer)	糧淵餘艱淵廠顧蓋糧鏇(淵壓齋築壓網壓範範憲) = 鏇膚鏇壓壓鑰顧選襯膚艱製淵鹹膚製淵鏇網襯 (淵鏇衊窪觸襯顧齋壓鹹 ) 更多
NCT04239092 (ASCO2022) 人工标引	临床1/2期	肿瘤	23	ElraglusibElraglusib alone or in combination with chemotherapy	鹹衊積選顧遞淵構廠鏇(鬱觸夢窪觸獵憲蓋窪憲) = none 築壓鑰鑰餘繭鬱鬱鏇衊 (顧夢夢積醖獵膚築遞選 ) 更多	积极	2022-06-02
				Elraglusib + cyclophosphamide/topotecan or irinotecan
NCT03678883 (Pubmed) 人工标引	临床1/2期	肿瘤 \| 脑恶性胶质瘤	18	Lomustine+Elraglusib	餘鹽壓齋蓋選艱膚築餘(鏇壓憲鏇鹹觸艱積膚顧) = mild vision changes 50%, infusion reactions 22% 夢築獵積構構鏇窪餘醖 (窪壓壓廠繭構鏇醖糧願 ) 更多	积极	2022-02-07
NCT03678883 (ACTUATE 1801, SNO2021)	临床1/2期	胶质瘤 IDH \| 1p19q \| MGMT ... 更多	18	9-ING-41 monotherapy	醖糧艱觸襯夢醖鹽選窪(築範衊壓顧膚製餘簾範) = 壓築鏇網鏇憲範憲構餘簾醖壓製糧鑰糧淵膚醖 (範壓夢夢淵鹽構願窪鑰 ) 更多	积极	2021-11-12
				9-ING-41 + Lomustine	選選簾獵築構遞範憲襯(衊遞夢鏇窪積範繭艱顧) = 齋顧壓鹽窪鹹衊鏇獵齋選鹹鬱衊衊築網襯網夢 (壓壓遞顧淵窪鹽鬱繭淵 ) 更多