Elraglusib Combo Yields Notable 24-Month Survival Benefit in Metastatic PDAC

Continued significant survival boosts were seen with the investigational small molecule GSK-3β inhibitor elraglusib (9-ING-41) plus gemcitabine/nab-paclitaxel (GnP) chemotherapy in patients with metastatic pancreatic ductal adenocarcinoma (PDAC), suggesting potential long-term clinical benefit for patients in the first-line setting.¹

Updated data from part 3B of the phase 2 Actuate-1801 trial (NCT03678883), presented this past weekend at the 2026 American Society of Clinical Oncology (ASCO) Gastrointestinal Cancers Symposium, revealed that overall survival (OS) was significantly enhanced with the elraglusib regimen compared with GnP alone. The elraglusib arm saw a median OS of 10.1 months vs 7.2 months in the GnP alone arm (HR, 0.62; P =.02), equating to a 38% reduced risk of death between the respective arms.

Furthermore, a near-doubling of 12-month survival was also achieved with the elraglusib regimen vs GnP alone (44.4% vs 22.3%), and at 24 months, the survival rate was nearly 5 times higher in the elraglusib arm compared with GnP alone (12.9% vs 2.6%).

“As of November 2025, [17] patients are still alive in the elraglusib/GnP arm, and [3] of them have remarkably passed the 24-month mark on first-line treatment, while no patients remain on GnP treatment alone,” said Dan Schmitt, CEO of Actuate Therapeutics, in a news release.¹ “Current patient survival for metastatic pancreatic cancer is less than 12 months, so our findings are especially encouraging. We look forward to building from this data and continuing to advance elraglusib for patients with this devastating disease.”

In terms of safety, elraglusib’s safety and tolerability profile was reported to be consistent with prior reports at the 9.3 mg/kg dose, with no new safety signals identified. In previous reports, common adverse events (AEs) reported more frequently with elraglusib included visual impairment and neutropenia.

This latest analysis reported similar rates of serious treatment-emergent AEs (TEAEs) between the elraglusib and GnP alone arms (56.1% vs 56.4%, respectively), as well as similar rates of TEAEs resulting in death (12.3% vs 16.7%, respectively). Additionally, the elraglusib arm had a slightly lower rate of grade 3 or higher TEAEs leading to treatment discontinuation compared with the GnP alone arm (16.8% vs 21.8%).

These findings reinforce data toplined in May 2025 and presented at the 2025 ASCO Annual Meeting, where the trial was confirmed to have met its primary end point and a favorable risk/benefit profile. Elraglusib even demonstrated potential for patients with liver metastases, a subgroup of patients who have historically faced a poor prognosis in metastatic PDAC. These latest data specifically highlight the durability of this clinically meaningful survival advantage for this patient population.

“Pancreatic cancer continues to have a high unmet medical need, particularly at the metastatic stage,” added Devalingam Mahalingam, MD, PhD, Northwestern Memorial Hospital and Northwestern University Feinberg School of Medicine, in a news release.¹ “The results from this [p]hase 2 study suggest that adding elraglusib to standard gemcitabine and nab-paclitaxel chemotherapy may improve survival outcomes while maintaining a manageable safety profile. The scope of this trial, which enrolled 286 patients across 60 sites in [6] countries, underscores the robustness of the dataset. We are grateful to the patients and their families whose participation made this research possible.”

The FDA granted orphan drug designation to elraglusib in pancreatic cancer in 2023.

Additional Findings: Biomarker Analyses

Beyond clinical outcomes, the study identified several actionable genomic and immunological biomarkers linked to improved outcomes among patients treated with elraglusib/GnP.

Several pancreatic cancer-associated mutations, including KRAS and ARID1A, correlated with OS in the combination arm but not with GnP alone, highlighting potential avenues for future combination strategies. Additionally, tumors from patients in the combination arm showed elevated levels of CD8-positive T cells, natural killer cells, and Granzyme B-positive cells, suggesting enhanced antitumor immune activity with the combination therapy. These biomarkers may help predict OS and antitumor response to inform personalized treatment strategies.

Actuate-1801 Study Design

The objective of the global phase 1/2 Actuate-1801 trial is to evaluate the safety and efficacy of elraglusib as a single agent and in combination with cytotoxic agents in patients with refractory hematologic malignancies or solid tumors.

The study has been conducted in 3 sequential parts, each evaluating different elraglusib regimens:

• Part 1: A dose-escalation stage with elraglusib monotherapy to identify the maximum tolerated dose (MTD) or recommended phase 2 dose (RP2D).
• Part 2: A dose-escalation stage assessing elraglusib combined with 8 standard chemotherapy regimens to identify the MTD/RP2D of each regimen.
• Part 3: A randomized phase 2 study of elraglusib/GnP combination therapy vs GnP alone for patients with previously untreated metastatic or locally advanced PDAC.

In part 3, patients assigned to the elraglusib arm received elraglusib intravenously over 60 minutes either once or twice weekly plus intravenous GnP.

REFERENCES

1. Actuate Therapeutics reports positive follow-up data from its randomized controlled phase 2 trial demonstrating extended long-term overall survival benefit with elraglusib plus chemotherapy for metastatic pancreatic cancer in an oral presentation at ASCO GI 2026. News release. Actuate Therapeutics. January 12, 2026. Accessed January 12, 2026. https://tinyurl.com/2s49xtw4

2. 9-ING-41 in patients with advanced cancers. ClinicalTrials.gov. Updated November 7, 2024. Accessed January 12, 2026. https://clinicaltrials.gov/study/NCT03678883