Elraglusib and chemotherapy in metastatic pancreatic ductal adenocarcinoma: a randomized controlled phase 2 trial.

Elraglusib (9-ING-41), an inhibitor of GSK-3β, exhibits a multimodal mechanism of action based on antitumor activity in preclinical models of cancer, including pancreatic.

Elraglusib（9-ING-41），一种GSK-3β抑制剂，根据其在包括胰腺在内的癌症的临床前模型中的抗肿瘤活性，展示了一种基于多模式机制的作用。

The efficacy and safety of elraglusib with gemcitabine plus nab-paclitaxel (GnP) were assessed in patients with previously untreated mPDAC.

在一项开放标签、国际、多中心的2期研究中，患者按2:1的比例随机接受每周elraglusib/GnP或单独GnP治疗。

In an open-label, international, multicenter, phase 2 study, patients were randomized 2:1 to weekly elraglusib/GnP or GnP alone.

在一个开放标签、国际、多中心的2期研究中，患者按2:1的比例随机分配接受每周一次的elraglusib/GnP治疗或仅接受GnP治疗。

Primary endpoints were median overall survival(OS) and 1-year survival rate.

主要终点是中位总生存期（OS）和1年生存率。

The prespecified modified intention-to-treatpopulation included 155 patients on elraglusib/GnP and 78 on GnP.

预先设定的改良意向治疗人群包括155名接受elraglusib/GnP治疗的患者和78名接受GnP治疗的患者。

As of the data cutoff of 27 April 2025, elraglusib/GnP improved median OS by 2.9 months and decreased the risk of death by 38% versus GnP (median OS 10.1 months versus 7.2 months, respectively (hazard ratio0.62; 95% confidence interval0.46 to 0.84; P = 0.01)).

截至2025年4月27日的数据截止日期，elraglusib/GnP将中位总生存期提高了2.9个月，并将死亡风险降低了38%，与GnP相比（中位总生存期分别为10.1个月和7.2个月，风险比为0.62；95%置信区间0.46至0.84；P = 0.01）。

The 1-year survival rates were 44.1% versus 22.3%, respectively.

1年生存率分别为44.1%和22.3%。

The safety profile of elraglusib/GnP was manageable.

elraglusib/GnP的安全性特征是可管理的。

The most common grade 3 or higher treatment-emergent adverse events (TEAEs) with elraglusib/GnP versus GnP alone were neutropenia (52.3% versus 30.8%), anemia (25.2% versus 29.5%) and fatigue (16.8% versus 5.1%).

与单独使用GnP相比，elraglusib/GnP治疗相关的最常见3级或更高级别的不良事件（TEAEs）是中性粒细胞减少症（52.3%对比30.8%）、贫血（25.2%对比29.5%）和疲劳（16.8%对比5.1%）。

Explorative correlative analyses demonstrated that baseline circulating immune-related factors (that is, CXCL2 and TRAIL ligands) were associated with improved survival in the elraglusib/GnP arm.

探索性相关性分析显示，基线循环免疫相关因子（即，CXCL2和TRAIL配体）与elraglusib/GnP组的改善生存相关。

Treatment was accompanied by increases in intratumoral cytotoxic immune cell populations.

治疗伴随着肿瘤内细胞毒性免疫细胞群体的增加。

Together, these findings support the clinical activity of elraglusib/GnP as first-line treatment in mPDAC and provide a biological context for the observed survival benefit.

这些发现共同支持了elraglusib/GnP作为转移性胰腺导管腺癌一线治疗的临床活性，并为观察到的生存益处提供了生物学背景。

Based on the results of this phase 2 trial, a phase 3 trial is being planned.

基于这项2期试验的结果，目前正在规划一项3期试验。

ClinicalTrials.gov registration: NCT03678883.

临床试验注册：NCT03678883。