June 17, 2026
Adding an experimental agent to the standard chemotherapy regimen of gemcitabine plus nab-paclitaxel (GnP) for metastatic pancreatic cancer improves survival, according to results from a recently published phase 2 randomized clinical trial. The results were published in Nature Medicine.
Tanios S. Bekaii-Saab, M.D., an oncologist at Mayo Clinic in Arizona, was the senior lead investigator for this multinational study. The team of investigators from Mayo Clinic also included Ryan M. Carr, M.D., Ph.D., and Taylor M. Weiskittel, M.D., Ph.D.
The trial evaluated the safety and efficacy of combining elraglusib, an inhibitor of glycogen synthase kinase-3 beta (GSK-3β), with GnP in patients with previously untreated metastatic pancreatic ductal adenocarcinoma (mPDAC). It found that patients who received elraglusib alongside GnP were twice as likely to be alive after one year of treatment compared with those treated with GnP alone. This is a "statistically significant improvement in survival," according to the study authors.
In addition, the safety profile of elraglusib plus GnP was manageable with modest increases in grade 3 adverse events. Researchers reported that their findings support the clinical use of elraglusib plus GnP as a first line treatment in mPDAC, with current planning for a phase 3 trial.
The rationale for targeting GSK-3β in pancreatic cancer
Metastatic pancreatic ductal adenocarcinoma represents over 90% of all pancreatic cancers. Yet despite its increasing incidence over the past decades and the identification of potential molecular driver alterations as targets — including BRCA1and BRCA2, PALB2, and K-ras — advances in treatments remain limited.
Past research published in Cancer Research highlights the role of GSK-3b in cell proliferation and survival pathways in pancreatic cancer. Once preclinical cancer models identified the serine-threonine kinase as a potential therapeutic target in human pancreatic cancer, pancreatic cancer models and early-phase clinical trials revealed promising results. The results showed that elraglusib inhibited cancer cell proliferation and survival, sensitized cancer cells to chemotherapy agents, and prevented chemoresistance.
The results were particularly noteworthy given the historical failure of targeted therapies evaluated in pancreatic cancer, including immune checkpoint inhibitors and antiangiogenic therapies.
Phase 2 trial demonstrates survival benefit with elraglusib combination
In the trial, researchers enrolled 233 patients at 60 cancer centers across North America and Europe. The patients were randomly assigned to receive GnP alone or GnP in combination with elraglusib.
Patients who received the combination lived a median of 10.1 months, compared with those who received only GnP and lived a median of 7.2 months. In addition, the combination treatment reduced the risk of death by 38%.
Researchers also found that survival at one year doubled among patients who received elraglusib — 44% versus 22% — and about 13% of patients remained alive at two years, compared with none in the GnP-only group.
The trial, built on two decades of research at Mayo Clinic to translate a GSK-3b inhibitor into a promising new treatment, represents the first evidence of the inhibitor's efficacy beyond early-stage testing.
Although the study's authors found that elraglusib may exacerbate side effects associated with GnP, such as low white blood cell counts and fatigue, they consider the safety profile of elraglusib plus GnP to be manageable. They are planning to confirm the findings in a phase 3 trial.
For more information
Mahalingam D, et al. Elraglusib and chemotherapy in metastatic pancreatic ductal adenocarcinoma: A randomized controlled phase 2 trial. Nature Medicine. 2026;32:1794.
Ougolkov AV, et al. Glycogen synthase kinase-3b participates in nuclear factor κB-mediated gene transcription and cell survival in pancreatic cancer cells. Cancer Research. 2005;65:2076.
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