Actuate Therapeutics Initiates Phase 1b Trial to Evaluate Novel Combination as Frontline Therapy for Advanced Pancreatic Adenocarcinoma

Strategic Insights -

Actuate Therapeutics, Inc. has initiated a Phase 1b trial to evaluate the safety and efficacy of a novel combination of its lead investigational drug, elraglusib, with Incyte's PD-1 inhibitor, retifanlimab, and modified FOLFIRINOX (mFOLFIRINOX) as frontline therapy in advanced pancreatic adenocarcinoma. The trial, led by Anwaar Saeed, MD, Associate Professor of Medicine, and Chief of the Gastrointestinal Medical Oncology at UPMC Hillman Cancer Center, will initially enroll up to 12 patients with advanced pancreatic adenocarcinoma, with an expansion plan based on interim efficacy results. The primary objective of the trial is to determine the recommended phase 2 dose (RP2D) for the combination regimen, while the secondary objectives include evaluation of overall response rate (ORR), disease control rate (DCR), median progression-free survival (mPFS), overall survival (OS), and assessment of safety and tolerability.

Key Takeaways:

  • The Phase 1b trial will evaluate a novel combination of elraglusib with retifanlimab and mFOLFIRINOX as frontline therapy in advanced pancreatic adenocarcinoma.
  • The trial will initially enroll up to 12 patients with advanced pancreatic adenocarcinoma, with an expansion plan based on interim efficacy results.
  • The primary objective of the trial is to determine the recommended phase 2 dose (RP2D) for the combination regimen.
  • The secondary objectives of the trial include evaluation of overall response rate (ORR), disease control rate (DCR), median progression-free survival (mPFS), overall survival (OS), and assessment of safety and tolerability.
  • The study is led by Anwaar Saeed, MD, Associate Professor of Medicine, and Chief of the Gastrointestinal Medical Oncology at UPMC Hillman Cancer Center.
  • A recent Phase 2 study showed that elraglusib in combination with gemcitabine/nab-paclitaxel (GnP) in first-line metastatic pancreatic adenocarcinoma resulted in a significant increase in median overall survival, a 37% reduction in the risk of death, and a doubling of the 12-month survival rate.
  • Elraglusib's proposed immune modulating mechanism of action has been demonstrated in tumor biopsies, showing increased CD8-positive and granzyme B-positive T cells, increased NK cells, and decreased myeloid-derived suppressor cells.
  • Actuate Therapeutics' lead investigational drug, elraglusib, targets molecular pathways in cancer that are involved in promoting tumor growth and resistance to conventional cancer drugs.

Statistics:

  • Up to 12 patients with advanced pancreatic adenocarcinoma will be enrolled in the Phase 1b trial.
  • The trial will have an expansion plan based on interim efficacy results.
  • The recommended phase 2 dose (RP2D) for the combination regimen is the primary objective of the trial.
  • Overall response rate (ORR), disease control rate (DCR), median progression-free survival (mPFS), overall survival (OS), and assessment of safety and tolerability are the secondary objectives of the trial.

Sources:

  • Actuate Therapeutics, Inc. press release, August 6, 2025.
  • Annual Report on Form 10-K for the year ended December 31, 2024, filed with the SEC on March 13, 2025.
  • Quarterly Report on Form 10-Q for the quarter ended March 31, 2025, filed with the SEC on May 15, 2025.