Elraglusib and chemotherapy in metastatic pancreatic ductal adenocarcinoma: a randomized controlled phase 2 trial
Paper cited by one trial page, indexed on Europe PMC as PubMed record 41981308 and published in Nature Medicine; the citing page links this DOI, which is how the record was matched.
Overview
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. at 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.
Indexed on Europe PMC as PubMed record 41981308 (DOI 10.1038/s41591-026-04327-4). Matched by DOI alone: one trial page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.
One trial page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.
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