elraglusib (9-ING-41) / Actuate Therap - LARVOL DELTA

A phase II study of FOLFIRINOX (FFX) combined with the glycogen synthase kinase-3beta (GSK-3β) inhibitor elraglusib (ELRA) and the transforming growth factor beta (TGFβ) inhibitor losartan (LOS) in patients with untreated metastatic pancreatic ductal adenocarcinoma (mPDAC). (ASCO 2026) - P2 | "Although clinical outcomes with the novel combinations did not exceed historical standards of care, this non-comparator phase II study demonstrates the feasibility and tolerability of combinatorial pathway inhibition in mPDAC. This study enables ongoing correlative analyses of EMT plasticity, stromal remodeling, and immune escape in mPDAC and establishes a robust platform to define determinants of resistance and durable response."

Clinical • Metastases • P2 data • Fibrosis • Infectious Disease • Oncology • Pancreatic Ductal Adenocarcinoma • Septic Shock • TGFB1

Post-hoc efficacy and biomarker analysis of elraglusib plus gemcitabine/nab-paclitaxel versus chemotherapy alone in metastatic pancreatic ductal adenocarcinoma. (ASCO 2026) - P2 | "The elevated early mortality in the GnP control arm reflects enrollment of a heterogeneous, real-world mPDAC population with less restrictive eligibility than recent registrational trials. Post-hoc analyses identify key clinical and molecular drivers of early death and confirm a consistent survival benefit with elraglusib/GnP. These hypothesis-generating findings directly inform eligibility criteria, stratification, and endpoint assumptions for the planned phase 3 trial."

Biomarker • Clinical • Metastases • Retrospective data • Oncology • Pancreatic Ductal Adenocarcinoma • CA 19-9 • CDKN2A • KRAS • TP53

Identification of potential immune biomarkers for GSK-3 inhibitor elraglusib (9-ING-41) in patients with relapsed/refractory metastatic cancer (AACR 2024) - P2 | "Part 1 and 2 predose samples were also analyzed separately, and many of the biomarkers identified in the aggregate analysis retained significance in the separated analysis. In Part 1, CXCL5, IFN-alpha, and IL-18 emerged as unique markers, and in Part 2, CCL22 was the single unique marker.The results of our exploratory study identified several putative biomarkers of elraglusib clinical benefit and demonstrated potential immunomodulatory mechanisms of elraglusib that will be used to inform the further clinical development of elraglusib for the treatment of metastatic cancer."

Biomarker • Clinical • Metastases • Oncology • CCL2 • CCL22 • CXCL5 • CXCL8 • FAS • IFNA1 • IL18 • TNFRSF10C

Phase II study of elraglusib (9-ING-41), a GSK-3β inhibitor, in combination with gemcitabine plus nab-paclitaxel in previously untreated metastatic pancreatic cancer. (PubMed, ESMO Open) - "Elraglusib/GnP showed preliminary clinical activity. In terms of safety, elraglusib resulted in a modest exacerbation of GnP-related toxicities, leading to a dose reduction of elraglusib to 9.3 mg/kg twice a week. Based on the initial efficacy and safety data, the study was amended to a randomized phase II study that will evaluate the 9.3 mg/kg dose."

Journal • P2 data • Fatigue • Hematological Disorders • Leukopenia • Neutropenia • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Solid Tumor

Preliminary results from the randomized phase 2 study (1801 part 3B) of elraglusib in combination with gemcitabine/nab-paclitaxel (GnP) versus GnP alone in patients (pts) with previously untreated metastatic pancreatic ductal adenocarcinoma (mPDAC). (ASCO 2025) - P2 | "The preliminary results showed a statistically significant benefit for 1-yr OS and mOS and favorable trends for ORR and DCR with elraglusib/GnP over GnP, with manageable safety profile. The mOS for GnP is lower relative to MPACT and NAPOLI-3 but comparable to recent real-world meta-analyses, explained by advanced disease burden and higher mortality rate in the first 4 months in our study. Topline analysis (April 2025) and correlative biomarker analysis predictive for OS will be presented."

Clinical • Combination therapy • IO biomarker • Metastases • P2 data • Anemia • Fatigue • Neutropenia • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • IFNB1 • PD-L1

Evaluation of antitumor activity of oral elraglusib in B16F10 melanoma model (EORTC-NCI-AACR 2026) - "Abstract will be available as of 4 November (with consent of the author)"

Melanoma • Oncology • Solid Tumor

Actuate Therapeutics, Inc…announced new preclinical data evaluating elraglusib in combination with zoldonrasib (RMC-9805), an investigational RAS(ON) G12D-selective inhibitor, and daraxonrasib (RMC-6236), a RAS(ON) multi-selective inhibitor, in pancreatic ductal adenocarcinoma (PDAC), including models resistant to FOLFIRINOX chemotherapy. (The Manila Times) - "Across murine KPC and human PDX-derived pancreatic cancer cell lines, the addition of elraglusib to zoldonrasib reduced cell growth beyond that observed with zoldonrasib alone across all models tested."

Preclinical • Pancreatic Ductal Adenocarcinoma

Results from the randomized phase 2 study (1801 Part 3B) of elraglusib plus gemcitabine/nab-paclitaxel (GnP) versus GnP in previously untreated metastatic pancreatic ductal adenocarcinoma (mPDAC). (ASCO-GI 2026) - P2 | "A significant benefit for 1-yr OS and mOS and a favorable trend for ORR were observed with the addition of elraglusib to GnP. The mOS was lower in the GnP arm vs historical studies, likely due to early deaths in the first 2 months, but aligns with mOS estimates in the real-world analysis with broad heterogeneous population. Our study included 19.7% pts with albumin 25% with CA 19.9 levels > 8,000 U/mL."

Clinical • Metastases • P2 data • Gastrointestinal Cancer • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • CD8 • CDKN2A • GZMB • TP53

Mutational analysis and identification of potential biomarkers in patients with metastatic pancreatic cancer treated with the combination of the GSK-3 inhibitor elraglusib and gemcitabine/nab-paclitaxel in the 1801 Part 3B phase 2 study. (ASCO-GI 2026) - P2 | "Our preliminary results identified KRAS and TP53 gene mutations as potential predictive biomarkers of clinical outcome in elraglusib/GnP-treated mPDAC patients. Updated OS data and mutational analysis will be included in the final presentation."

Biomarker • Clinical • Metastases • P2 data • Gastrointestinal Cancer • Oncology • Pancreatic Adenocarcinoma • Pancreatic Cancer • Solid Tumor • CDKN2A • KRAS • TP53

Therapeutic Targeting of Epithelial Mesenchymal Cellular Plasticity in Pancreatic Cancer. (PubMed, Clin Cancer Res) - P2 | "GSK-3b blockade synergizes with FFX by modulating PDAC plasticity while promoting the development of a tumor suppressive immune microenvironment."

Journal • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Solid Tumor • CD4 • CD8 • CEACAM6 • FN1 • TGFB1

Evaluate Preliminary Anti-tumor Activity of Elraglusib in Adult Participants With Advanced Solid Tumors (clinicaltrials.gov) - P1/2 | N=100 | Not yet recruiting | Sponsor: Actuate Therapeutics Inc.

New P1/2 trial • Oncology • Solid Tumor

Endothelial glycogen synthase kinase 3β promotes dendritic cells maturations and drives liver inflammation and fibrosis in metabolic dysfunction-associated steatohepatitis (EASL 2026) - "Parallel studies used high-fat, fructose, and cholesterol (FFC)-fed mice treated with the GSK3 inhibitor elraglusib... Endothelial GSK3β drives lipotoxic endotheliopathy in MASH by promoting mitochondrial dysfunction, CXCL10-mediated DC maturation, and proinflammatory signaling. Genetic or pharmacological inhibition of GSK3β mitigates hepatic inflammation, fibrosis, and vascular dysfunction. Hence, targeting endothelial GSK3β is as a promising therapeutic approach in human MASH."

Cardiovascular • Fibrosis • Hepatology • Immunology • Inflammation • Liver Cirrhosis • Metabolic Disorders • Metabolic Dysfunction-Associated Steatohepatitis • Portal Hypertension • CD80 • CD86 • CXCL10 • GSK3B • ICAM1

Actuate Therapeutics’ Elraglusib Selected for Evaluation in BEACON2 Trial for High-Risk Pediatric Neuroblastoma (GlobeNewswire) - "BEACON2 is a landmark European multi-arm, multi-stage Phase 1/2 platform trial....Under the BEACON2 trial design, the combination of elraglusib with dinutuximab beta plus chemotherapy will initially be assessed in a dose confirmation cohort of up to 20 patients to evaluate safety and to determine the maximum tolerated dose (MTD), recommended Phase 2 dose (RP2D), and pharmacokinetics (PK) profile of the regimen. Following successful completion of the dose confirmation stage, the regimen may advance into a randomized portion of the platform trial, where approximately 75 patients will be enrolled with a planned interim analysis."

Trial status • Neuroblastoma

Title: A Phase II Study of FOLFIRINOX (FFX) Combined with the Glycogen Synthase Kinase-3 Beta (GSK-3β) Inhibitor Elraglusib (ELRA) and the Transforming Growth Factor-β (TGF-β) Inhibitor Losartan (LOS) in Patients with Untreated Metastatic Pancreatic Ductal Adenocarcinoma (mPDAC) (Yahoo Finance) - "Arms incorporating elraglusib demonstrated meaningful improvement: elraglusib/FFX and elraglusib/FFX+LOS each achieved mOS of 9.8 months and mPFS of 6.0 and 6.5 months, respectively, vs 7.7 months and PFS of 5.1 with FFX alone; A subset of patients in elraglusib combination arms demonstrated deep and durable responses, with ongoing biomarker analyses evaluating features associated with long-term benefit; The combination was generally well tolerated. Grade 3 or higher treatment-related adverse events occurred in 34.7% of patients, with the most common being diarrhea, fatigue, hypokalemia, and decreased platelet count, a profile consistent with the known toxicities of FOLFIRINOX, further supporting the tolerability of elraglusib."

P2 data • Pancreatic Ductal Adenocarcinoma

Title: Post-hoc efficacy and biomarker analysis of elraglusib plus gemcitabine/nab-paclitaxel versus chemotherapy alone in metastatic pancreatic ductal adenocarcinoma (Yahoo Finance) - "A comprehensive post-hoc efficacy and biomarker analysis of the randomized Phase 2 1801 Part 3B study showed that elraglusib plus gemcitabine/nab-paclitaxel (GnP), compared with GnP alone, provided meaningful clinical benefit across multiple patient subgroups in previously untreated mPDAC...Patients with KRAS WT treated with elraglusib/GnP achieved a mOS of 16.9 vs 10.1 months (p<0.001), a nearly 7-month improvement...This survival advantage was consistent across key tumor suppressor gene subgroups analyzed: TP53 WT: 13.4 vs 7.6 months, (p=0.002); CDKN2A WT: 10.4 vs 7.6 months, (p=0.002); SMAD4 WT: 10.1 vs 7.1 months, (p=0.003); Positive OS trends were observed in both the intent-to-treat (ITT) and modified intent-to-treat (mITT) populations treated with elraglusib plus GnP versus GnP alone."

Biomarker • P53mut • Retrospective data • Pancreatic Ductal Adenocarcinoma

Targeting the GSK-3β/mTOR axis to overcome chemoresistance in gestational choriocarcinoma: molecular mechanisms and therapeutic opportunities. (PubMed, Cancer Chemother Pharmacol) - "We analyze how crosstalk between GSK-3β and mTOR complexes (mTORC1/mTORC2) creates a resistant phenotype that limits the efficacy of conventional cytotoxic agents such as methotrexate, actinomycin D, and etoposide. Importantly, we highlight emerging therapeutic strategies to target this axis, including GSK-3β activators (lithium, 9-ING-41), mTOR inhibitors (rapamycin analogs, dual PI3K/mTOR inhibitors), and combination regimens that synergistically restore chemosensitivity. Preclinical data from trophoblastic and related malignancies demonstrate that dual targeting of GSK-3β and mTOR can reverse resistance phenotypes and enhance treatment responses. This comprehensive review provides a translational framework for developing molecularly targeted therapies in chemoresistant gestational choriocarcinoma, with potential implications for personalized treatment algorithms and clinical trial design in this rare but highly treatable malignancy."

Journal • Review • Oncology • Solid Tumor • GSK3B

Elraglusib, a glycogen synthase kinase 3 beta (GSK 3β) inhibitor, plus chemotherapy with or without immunotherapy for advanced salivary gland cancer (AACR 2025) - P2 | "Pts in cohort 1 received elra (15 mg/kg IV days 1, 4) with carboplatin (AUC 5 IV day 1) or cisplatin (75 mg/m2 IV day 1) every 21-days grouped by adenoid cystic carcinoma (ACC) or non-ACC histology...ORR was 9.4% (95%CI, 2-25) with partial responses (PR) in 3 pts (all non-ACC pts, having received pembrolizumab and cisplatin), while 19 (59%) pts had stable disease... Elraglusib with platinum chemotherapy and immune priming was well tolerated. While the primary endpoint was not met, anti-tumor activity was observed among 18% (3/17) of non-ACC pts warranting further investigation."

IO biomarker • Metastases • Adenoid Cystic Carcinoma • Oncology • Salivary Gland Cancer • GH1 • PD-L1

Inhibition of GSK3B signaling in pediatric brain tumors (AACR 2026) - "In vivo studies showed a significant improvement in overall survival in mice treated with 9-ING-41 increased survival from 35 days to 55 days (P < 0.0001). Mechanistic evaluation of tumor tissues revealed increased p53 expression and marked downregulation of Ki-67, indicating reduced proliferative activity."

Clinical • Brain Cancer • Embryonal Tumor • Oncology • Rhabdoid Tumor • Sarcoma • Solid Tumor

Elraglusib and chemotherapy in metastatic pancreatic ductal adenocarcinoma: a randomized controlled phase 2 trial. (PubMed, Nat Med) - P2 | "The efficacy and safety of elraglusib with gemcitabine plus nab-paclitaxel (GnP) were assessed in patients with previously untreated mPDAC. Based on the results of this phase 2 trial, a phase 3 trial is being planned. ClinicalTrials.gov registration: NCT03678883."

Journal • P2 data • Fatigue • Hematological Disorders • Neutropenia • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma

Experimental drug doubles one-year survival in pancreatic cancer (The Economic Times) - "The first group was treated with standard chemotherapy by itself, while others received chemotherapy with the drug elraglusib...The findings were shocking. The patients who were treated with the combined treatment experienced an average survival time of 10.1 months, as opposed to 7.2 months for patients receiving chemotherapy on its own. In addition the 42 percent of patients who received elraglusib remained living a year after being diagnosed as opposed to only 22 percent for the chemotherapy-only treatment group."

P2 data • Pancreatic Cancer

Elraglusib/GnP Improves Survival in Metastatic Pancreatic Adenocarcinoma (Drugs.com) - "'While these results will need to be confirmed in phase 3 trials, observing survival benefit in such a difficult-to-treat cancer is encouraging,' Mahalingam said in a statement. 'Given the novel mechanism of this drug, these findings raise the possibility that it could have broader application across other tumor types.'"

Media quote

FOLFIRINOX + Elraglusib + Losartan In Pancreatic Cancer (clinicaltrials.gov) - P2 | N=70 | Active, not recruiting | Sponsor: Colin D. Weekes, M.D., PhD | Trial completion date: Jul 2026 ➔ Dec 2026 | Trial primary completion date: Dec 2025 ➔ Dec 2026

Trial completion date • Trial primary completion date • Oncology • Pancreatic Adenocarcinoma • Pancreatic Cancer • Solid Tumor • UGT1A1

Genome wide CRISPR/Cas9 library screening identifies aurora kinase A as a regulator of elraglusib sensitivity in pancreatic cancer (AACR 2024) - "In addition, data from phase II clinical trials in patients with previously untreated metastatic pancreatic cancer is demonstrating preliminary evidence of clinical benefit in patients receiving a combination of gemcitabine/nab-paclitaxel. Strikingly, the AURKA inhibitor, alisertib, works synergistically with elraglusib to inhibit PDAC cell line growth and induce apoptosis. In summary, our results demonstrate that targeting AURKA is an effective approach to sensitize PDAC tumors to elraglusib."

Gastrointestinal Cancer • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Solid Tumor • AURKA • PLK1

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 (GlobeNewswire) - "7-40X increases in tumor-infiltrating cytotoxic immune cells and biomarker signals in the elraglusib arm reflect immunomodulatory mechanisms of action...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%."

P2 data • Pancreatic Ductal Adenocarcinoma

Actuate 1801: 9-ING-41 in Patients With Advanced Cancers (clinicaltrials.gov) - P2 | N=350 | Active, not recruiting | Sponsor: Actuate Therapeutics Inc. | Trial completion date: Jan 2026 ➔ Jun 2026 | Trial primary completion date: Jan 2025 ➔ Jun 2026

Trial completion date • Trial primary completion date • Brain Cancer • Breast Cancer • Colorectal Cancer • Glioblastoma • Glioma • Hematological Malignancies • High Grade Glioma • Kidney Cancer • Leukemia • Lung Cancer • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Osteosarcoma • Pancreatic Cancer • Renal Cell Carcinoma • Sarcoma • Solid Tumor • T Acute Lymphoblastic Leukemia • BCL2