On April 14, 2026 Actuate Therapeutics, Inc. (NASDAQ: ACTU) ("Actuate" or the "Company"), a clinical-stage biopharmaceutical company focused on developing therapies for the treatment of high-impact, difficult-to-treat cancers through the inhibition of glycogen synthase kinase-3 beta (GSK-3β), reported the publication of new data in Nature Medicine from a randomized phase 2 clinical trial (NCT03678883) evaluating elraglusib in combination with the gemcitabine-Nab-paclitaxel (GnP) chemotherapy compared to GnP alone in patients with previously untreated metastatic pancreatic cancer. The peer-reviewed paper (DOI: 10.1038/s41591-026-04327-4), entitled "Elraglusib and Chemotherapy in Metastatic Pancreatic Ductal Adenocarcinoma: A Randomized Controlled Phase 2 Trial" is available here.
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"These Phase 2 results continue to reinforce elraglusib’s potential as a combination-ready, first-line therapy with the ability to enhance the activity of standard of care chemotherapeutic backbones," said Daniel Schmitt, Chief Executive Officer of Actuate. "The significant improvement in overall survival with an acceptable safety profile marks an important milestone for patients facing metastatic pancreatic cancer, historically one of the most difficult to treat diseases. The elraglusib containing regimen delivered a 40% improvement in median overall survival, a 38% lower risk of death, and doubled the survival rate at one year compared to the current first-line chemotherapy regimen of GnP alone.
By targeting a central signaling node such as GSK-3β, elraglusib may modulate tumor cell survival, reshape tumor microenvironment, and suppress adaptive resistance pathways, enabling a broader biological impact across a broad range of cancers. Importantly, we are also advancing our research focused on exploring the expected synergistic potential of elraglusib in combination with RAS and MEK/RAF inhibitors, with the goal of further enhancing anti-tumor activity and broadening elraglusib’s therapeutic potential for patients. We remain deeply committed to advancing treatments that can improve patients’ lives and are grateful to the investigators and families who made this study possible."
Pancreatic cancer remains one of the deadliest malignancies worldwide. Pancreatic ductal adenocarcinoma (PDAC), which accounts for the majority of cases, is often diagnosed at a metastatic stage, where survival outcomes remain poor. For these patients, GnP is a commonly used first‑line regimen, yet median overall survival typically remains limited to approximately seven to ten months. Despite advances in understanding the molecular drivers of pancreatic cancer, meaningful therapeutic progress has been scarce, and immunotherapies successful in other solid tumors have not delivered similar benefits in PDAC, highlighting the urgent need for novel treatment approaches.
Elraglusib (9‑ING‑41), a first‑in‑class GSK‑3β inhibitor, was evaluated in combination with GnP in a global, open‑label, phase 2 study in previously untreated metastatic pancreatic ductal adenocarcinoma. Patients were randomized 2:1 to receive elraglusib plus GnP or GnP alone. The combination improved median overall survival to 10.1 months versus 7.2 months and reduced the risk of death by 38% (HR 0.62; p=0.01), with one‑year survival rates of 44.1% and 22.3%, respectively. Safety was generally manageable in the elraglusib/GnP combination, with the most common Grade ≥3 adverse events including neutropenia, anemia, and fatigue. Exploratory analyses identified cytokine biomarkers and immune‑cell changes consistent with the immunomodulatory effect of elraglusib.
Key Highlights and Readouts:
Among the 286 patients enrolled across 60 global sites, efficacy analyses focused on 155 patients treated with once‑weekly elraglusib plus GnP and 78 patients receiving GnP alone in the modified intent‑to‑treat population, the study’s prespecified population for efficacy and safety analyses.
Median overall survival (OS) was 10.1 months in the elraglusib/GnP arm (95% CI, 7.7–12.5) vs 7.2 months on the GnP arm (95% CI, 5.7–9.0), corresponding to a 2.9‑month improvement and a 38% reduction in risk of death (HR 0.62; p=0.01).
A 1-year survival rate of 44.1% was observed in patients receiving elraglusib/GnP compared with 22.3% treated with GnP alone; at 18 and 24 months, landmark survival rates were 20.5% and 13.2% vs 4.4% and 0%, respectively.
Survival benefits were consistent across poor prognosis subgroups; in patients with liver metastases, median OS was 8.3 vs 6.6 months (HR 0.62; p=0.008), and 1‑year survival rates were 39.2% vs 15.2%.
Exploratory immunophenotyping demonstrated 7–40X increases in intratumoral CD8⁺ T cells, granzyme‑B⁺ cells, and CD56⁺ NK cells following elraglusib/GnP, with no comparable increases observed with GnP alone.
High pre‑dose cytokine levels correlated with improved survival only in the elraglusib/GnP arm, indicating emerging predictive biomarker associations.
The combination was well tolerated; the most common ≥Grade 3 TEAEs with elraglusib/GnP vs GnP were neutropenia (52.3% vs 30.8%), anemia (25.2% vs 29.5%), and fatigue (16.8% vs 5.1%). The mild to moderate visual changes observed in the elraglusib arm were transient and reversible.
"Metastatic pancreatic cancer remains one of the most therapeutically challenging solid tumors, with few interventions demonstrating meaningful improvements in survival," said Dr. Devalingam Mahalingam, MD, PhD, lead author of the manuscript. "The 2.9-month improvement in median overall survival observed with elraglusib plus gemcitabine and nab-paclitaxel, together with early and sustained signals of benefit across poor-prognosis subgroups, is encouraging and supports further clinical evaluation. The observed increases in tumor-infiltrating cytotoxic immune cells provide preliminary biologic context for the clinical findings and raise the possibility of an immunomodulatory effect, although these exploratory observations will require confirmation in future studies. Collectively, these results provide a rationale for continued investigation of elraglusib-based combinations in pancreatic cancer and potentially other difficult-to-treat malignancies."
(Press release, Actuate Therapeutics, APR 14, 2026, View Source [SID1234664390])