Pancreatic cancer continues to pose significant challenges, with limited treatment options available, particularly for metastatic cases. Five years after the late television host Alex Trebek publicly revealed his battle with stage IV metastatic pancreatic cancer, the landscape of therapies remains sparse. According to the American Cancer Society, metastatic cases account for approximately 80–85% of all pancreatic cancer diagnoses, with a five-year survival rate tragically low at just 3% for distant pancreatic cancer. The treatment market, however, is projected to grow from $2.92 billion last year to $5.84 billion by 2030, reflecting a compound annual growth rate of 12.3%, as reported by Grand View Research.
Amid these daunting statistics, Actuate Therapeutics is working to change the narrative. The company is investigating elraglusib, a compound that has shown promising results in clinical trials for treating pancreatic cancer. Actuate’s pipeline includes both injection and oral forms of elraglusib, which has generated positive clinical data in patients diagnosed with this aggressive cancer.
At the recent American Society of Clinical Oncology (ASCO) Annual Meeting, Actuate presented positive topline data from the Phase II Actuate-1801 Part 3β trial (NCT03678883). This trial evaluated elraglusib in combination with the chemotherapy regimen of gemcitabine/nab-paclitaxel (GnP) in first-line metastatic pancreatic ductal adenocarcinoma (mPDAC). The results revealed a median overall survival increase of 10.1 months for patients receiving the combination treatment, compared to 7.2 months for those on GnP alone. This translates to a 37% reduction in the risk of death.
In a subset of 29 efficacy evaluable patients, elraglusib demonstrated a median overall survival of 15.3 months, with complete responses confirmed in two patients and partial responses in nine others. When factoring in a separate single-arm trial, elraglusib has produced four complete responses among over 200 patients.
Data from the Actuate-1801 trial compares favorably with historical benchmarks, including the median overall survival of 8.5 months in the 2013 MPACT trial and 11.1 months from the 2020-21 NAPOLI 3 trial. Daniel M. Schmitt, Actuate’s president and CEO, emphasized the significance of these findings, stating, “Everything points at this drug being highly active and meeting the endpoint the FDA is most interested in, which is increase in overall survival. There has been no meaningful advance in pancreatic cancer in the last 13 years. This would be the first one.”
Actuate has submitted its data as part of an amended investigational new drug (IND) application and plans to support regulatory submissions with both the FDA and the European Medicines Agency (EMA) by the end of this year and into early 2026. The company is also pursuing Breakthrough Therapy designation from the FDA, aiming to demonstrate a substantial improvement in treatment over existing standard therapies.
The Actuate-1801 trial enrolled 286 patients with mPDAC and no prior systemic treatment for metastatic disease, who were randomized in a 2:1 ratio to receive either the elraglusib/GnP combination or GnP alone. The trial remains ongoing, with recent reports indicating that 22 patients in the elraglusib plus GnP arm have been in active treatment or survival follow-up for periods ranging from 20 to 42 months. In comparison, only three patients in the GnP arm were on study for 21 to 23 months.
Actuate-1801 is one of three ongoing trials assessing elraglusib in combination with chemotherapy. A Phase II trial led by researchers from Harvard Medical School and Massachusetts General Hospital is evaluating elraglusib alongside Folfirinox and losartan in patients with metastatic pancreatic cancer. Additionally, the company is collaborating with UPMC Hillman Cancer Center and Incyte on the Phase I RiLEY trial, which studies elraglusib with a modified version of Folfirinox and Incyte’s PD-1–blocking antibody, Zynyz® (retifanlimab-dlwr).
Schmitt remarked on the potential of elraglusib to serve as a new backbone therapy for pancreatic cancer, stating, “It’s a very unique situation with elraglusib, a drug that has the potential to be the new backbone therapy in this highly aggressive and deadly disease.” The current standard of care for pancreatic cancer varies based on the stage of the disease, with early-stage resectable tumors typically removed via surgery, while advanced or metastatic cases usually result in chemotherapy.
As the landscape evolves, Swiss-based Novocure anticipates approval for its Tumor Treating Fields (TTFields) wearable device in the second half of 2026, which is currently under FDA review for locally advanced pancreatic cancer. In the past year, two therapies have received FDA approval for pancreatic cancer, including Bizengri®, a bispecific HER2- and HER3-directed antibody, and Cabometyx®, a kinase inhibitor for specific pancreatic neuroendocrine tumors.
Elraglusib, identified as a selective small-molecule inhibitor of glycogen synthase kinase-3 beta (GSK-3β), targets molecular pathways involved in cancer growth and resistance to treatment. Initially developed through research at the University of Illinois Chicago (UIC) and Northwestern University, elraglusib was synthesized to selectively inhibit GSK-3β, thereby reducing tumor cell survival.
Beyond pancreatic cancer, Actuate is exploring the potential of elraglusib in other cancer types, such as colorectal cancer and melanoma, with plans for Phase I trials underway. The company has also identified Ewing sarcoma as a potential indication for elraglusib injection, with plans for a Phase II study anticipated in 2026, contingent upon funding.
Despite a net loss of $5.407 million in the third quarter of 2024, Actuate’s financial position has improved, reporting cash and cash equivalents of $16.925 million, nearly double from the previous year. This growth follows a series of capital-raising events, including a $17.25 million public offering in September 2024.
Actuate’s future strategies hinge on FDA feedback regarding elraglusib. Depending on the response, the company may expand its workforce and regulatory staff to prepare for potential New Drug Application submissions. Schmitt indicated that Actuate is pursuing both organic growth and potential merger-and-acquisition opportunities, ensuring the company is prepared to advance its innovative therapies for pancreatic cancer and beyond.
With ongoing trials and promising data, Actuate Therapeutics is positioning itself as a pivotal player in the fight against pancreatic cancer, aiming to bring new hope to patients facing this formidable disease.
