Actuate Therapeutics announces interim Phase 2 data of elraglusib

Actuate Therapeutics (ACTU) announced data from its ongoing and fully enrolled randomized Phase 2 trial of elraglusib in combination with gemcitabine/nab-paclitaxel in first line treatment of metastatic pancreatic ductal adenocarcinoma. A pre-specified analysis was triggered by reaching greater than70% death events in the GnP control arm. The analysis of interim data demonstrated treatment with elraglusib in combination with GnP resulted in statistically significant increases in 1-year survival rate and median overall survival versus treatment with GnP alone. The combination treatment also resulted in increased Objective Response Rates and Disease Control Rates in the elraglusib/GnP combination arm versus the GnP control arm. Inhibition of GSK-3beta may inhibit tumor growth and improve survival through several complimentary mechanisms that include enhancement of chemotherapy activity, activation of innate anti-tumor immunity and regulation of gene expression, leading to alterations in tumor metabolism and Epithelial-to-Mesenchymal Transition. Study highlights include: The interim data met the trial primary endpoint with a 1-year survival rate of 43.6% in the elraglusib-GnP combination arm versus 22.5% in the GnP control arm; Eighteen and twenty-four month survival rates also demonstrated benefit of 20.9% vs 0% and 16.7% vs 0% in the elraglusib-GnP combination vs GnP arms, respectively. As of the November 15, 2024 cutoff, 38% of subjects were still alive in the elraglusib-GnP combination arm vs 19% in the GnP control arm. A statistically significant 37% reduction in risk of death and increased median overall survival were observed in the elraglusib-GnP combination arm vs the GnP control arm. The trial also met its primary safety endpoint. Treatment-emergent adverse events and Serious Adverse Events in the elraglusib-GnP combination arm were similar to those observed in the GnP arm, indicating a favorable risk-benefit profile for the elraglusib-GnP combination. At the interim cutoff of November 15, 2024, the ORR was 27.7%, DCR was 42.6 %, and PFS was 5.6 months in the elraglusib-GnP combination arm versus 20.5%, 33.3% and 4.9 months in the GnP arm, respectively. To date, there have been 2 patients in the elraglusib/GnP combination arm with previously inoperable metastatic lesions with noted reductions in target lesions and referred for successful resection, 1 of which resulted in 100% reduction in total tumor burden after surgery. In addition, there have been 1 Complete Response and 1 Partial Response with 100% reduction in target lesions in the elraglusib GnP combination arm versus 0 in the control arm to date. The ongoing Actuate-1801 Part 3B study is a randomized, controlled Phase 2 trial of elraglusib with GnP versus GnP alone in first line mPDAC. The trial enrolled 286 mPDAC patients with no prior systemic treatment for metastatic disease, who were randomized 2:1 to the elraglusib treatment arm or the control arm. Elraglusib is administered at a dose of 9.3 mg/kg by IV infusion on Day 1 of each week of a 28-day cycle. The primary endpoint is 1-year survival rate, with mOS the primary parameter for summarization of survival data at the end of the study. Secondary endpoints are DCR, ORR, PFS and AE.