Announcement • Apr 16
Actuate Therapeutics Announces Nature Medicine Publication of Clinical Trial Results Showing Doubling of the Rate of Survival with Elraglusib Plus Chemotherapy in Previously Untreated Metastatic Pancreatic Ductal Adenocarcinoma
Actuate Therapeutics, Inc. (“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-3ß), announced 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. Median overall survival increased by >40% in elraglusib arm compared to the control arm, with a 1-year survival rate of 44% in the elraglusib arm versus 22% in the control arm. 18-month survival rate >20% in elraglusib arm compared to 4% in control arm. Consistent survival benefit observed across the poorest prognosis patient subgroups, including those with liver metastases and high disease burden. 7-40X increases in tumor-infiltrating cytotoxic immune cells and biomarker signals in the elraglusib arm reflect immunomodulatory mechanisms of action. 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. Elraglusib (9-ING-41), a first-in-class GSK-3ß 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. 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.
