Elraglusib and chemotherapy in metastatic pancreatic ductal adenocarcinoma: a randomized controlled phase 2 trial
Summary
Metastatic pancreatic ductal adenocarcinoma (mPDAC) is one of the leading causes of cancer-related mortality, but advances in therapeutic treatments remain limited. 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. The efficacy and safety of elraglusib with gemcitabine plus nab-paclitaxel (GnP) were assessed in patients with previously untreated mPDAC. In an open-label,
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# Elraglusib and chemotherapy in metastatic pancreatic ductal adenocarcinoma: a randomized controlled phase 2 trial
*Published: 2026 May*
Metastatic pancreatic ductal adenocarcinoma (mPDAC) is one of the leading causes
of cancer-related mortality, but advances in therapeutic treatments remain
limited. 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. The efficacy and safety of elraglusib with gemcitabine
plus nab-paclitaxel (GnP) were assessed in patients with previously untreated
mPDAC. In an open-label, international, multicenter, phase 2 study, patients
were randomized 2:1 to weekly elraglusib/GnP or GnP alone. Primary endpoints
were median overall survival (OS) and 1-year survival rate. The prespecified
modified intention-to-treat population included 155 patients on elraglusib/GnP
and 78 on GnP. 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 ratio 0.62; 95%
confidence interval 0.46 to 0.84; P = 0.01)). The 1-year survival rates were
44.1% versus 22.3%, respectively. The safety profile of elraglusib/GnP was
manageable. 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%). 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. Treatment was accompanied by increases in
intratumoral cytotoxic immune cell populations. 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. Based on the
results of this phase 2 trial, a phase 3 trial is being planned.
ClinicalTrials.gov registration: NCT03678883.
DOI: 10.1038/s41591-026-04327-4