2025-08-25
Actuate Therapeutics Advances A New Era In Oncology With Potential Universal Backbone Therapy
Vexing challenges await cancer researchers every day — not just in finding new molecules — but now, increasingly, in finding new ways to make tumors more vulnerable to existing drugs.Tumors have their own defense mechanisms, designed to thwart therapeutic intruders, and the immune system is often unable to mount an effective response. Image credit: Shutterstock.Dozens of companies are working in this area but Actuate Therapeutics (NASDAQ:ACTU) reports it has made more progress than any other, especially when it comes to difficult-to-treat tumors like metastatic ductal pancreatic cancer.One current standard of care for this diagnosis is gemcitabine combined with nab-paclitaxel, a drug developed 13 years ago by Celgene as Abraxane (now owned by Bristol-Myers Squibb (NYSE: BMY). It won FDA approval after a phase 3 trial showed that the combination (generically called GnP) increased overall survival of metastatic pancreatic cancer patients by nearly two months (8.5 vs. 6.7) compared to gemcitabine alone. GnP still remains one of the most widely prescribed front-line chemotherapeutics for pancreatic cancer, with $1.8 billion in sales last year. In cancer research, building on key advances can be a productive strategy.So, armed with that idea and a large body of preclinical and mechanistic data, Actuate created a program that would add a third agent — its GSK-3β inhibitor elraglusib (elra) – to the GnP combination with the goal of creating a new first-line therapy that could achieve better outcomes than GnP alone in the setting of metastatic pancreatic cancer.Game-Changing ResultsThe plan paid off. At this year's ASCO, Actuate reported positive topline results of a 286-patient phase 2 clinical trial of elra+GnP in metastatic ductal pancreatic cancer patients randomized 2:1 to elra+GnP or GnP alone.–For patients in the elra+GnP arm, median overall survival increased by almost three months to 10.1 months vs 7.2 months for GnP alone, with an overall 37% reduction in the risk of death. –44.1% of patients in the elra+GnP arm were alive at Year 1, double the number (22.3%) in the GnP alone arm.The results suggest a promising end to a 13-year drought of major advances in treating metastatic pancreatic cancer, and the potential of a new platform for boosting drug performance in many other malignancies. A layman's explanation of what is happening might read something like this: elra appears to have the ability to make cold tumors hot/more visible to the patient's immune system, amping up a targeted immune response and downregulating the tumor's natural defenses, enabling anti-cancer agents to penetrate tumors and kill malignant cells faster and deeper than previously possible. Such features may also finally make checkpoint immune therapy effective in pancreatic tumors, typically among the "coldest" of all.With Notable DurabilityThe benefits of Actuate's elra were also compelling at 18 and 24 months. The 18-month survival rate was 19.7% for the elra+GnP arm vs. 4.4% for the GnP alone arm. At 24 months, 13.8% of patients in the elra+GnP arm were alive vs. none in the GnP alone arm. There were even some cases in which investigators said patients on elra+GnP became eligible for Whipple procedures, complex surgeries to remove the head of the pancreas. That's typically not the case for patients getting chemotherapy alone. "Based on the clear clinical benefit and a ...Full story available on Benzinga.com
