Actuate Therapeutics (ACTU) Study update summary

Study background and design

• Phase II randomized, controlled trial evaluated elraglusib in first-line metastatic pancreatic cancer across multiple centers, enrolling 286 patients with a 2:1 randomization.

• The study included a broad patient population with minimal restrictions, reflecting real-world diversity.

• The trial compared elraglusib plus standard chemotherapy backbones (gemcitabine/nab-paclitaxel or FOLFIRINOX), with primary endpoint of median overall survival and secondary endpoints including disease control rate, overall response rate, progression-free survival, and adverse events.

• Elraglusib targets GSK-3 beta, impacting EMT, immune modulation, and tumor stroma.

• The study is one of the largest phase II randomized trials in this setting.

Key efficacy and survival findings

• Median overall survival improved to 10.1 months with elraglusib/GnP versus 7.2 months with GnP alone (HR=0.63, p=0.01), representing a 37% reduction in risk of death.

• One-year survival rate doubled to 44.1% with elraglusib/GnP compared to 22.3% with GnP alone; continued survival benefit observed at 18 and 24 months (19.7% vs 4.4% and 13.8% vs 0%, respectively).

• Numerically higher overall response rate (29.0% vs 21.8%), median progression-free survival (5.6 vs 5.1 months), and median duration of response (5.5 vs 4.0 months) in the elraglusib/GnP arm.

• Survival benefit becomes more pronounced after the initial two months, especially in patients completing at least one cycle.

• Landmark survival rates and the tail of the survival curve are notably improved, with some patients exceeding one year.

Safety and tolerability

• Safety profile of elraglusib/GnP was similar to GnP alone, with most treatment-related adverse events being Grade 1-2 and reversible.

• Most frequent adverse event was transient, non-progressive visual impairment; rates of febrile neutropenia and sepsis were similar between arms.

• Increased neutropenia was observed but did not translate to febrile neutropenia or sepsis.

• No significant additive toxicity was seen when combined with standard chemotherapy.

• Patients often reported improved quality of life and ability to resume normal activities.