First-Line Elraglusib Plus Chemo Improves Survival in Metastatic Pancreatic Cancer

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The addition of the GSK-3β inhibitor elraglusib (9-ING-41) b to gemcitabine and nab-paclitaxel (Abraxane) led to a statistically significant improvement in overall survival (OS) compared with chemotherapy alone in the first-line treatment of patients with metastatic pancreatic ductal adenocarcinoma (PDAC), according to topline data from part 3B of the phase 2 Actuate-1801 trial (NCT03678883).1

Findings showed that study met its primary end point with significant improvements in median OS and 1-year OS rate in the experimental arm. The risk:benefit profile of elraglusib in combination with gemcitabine and nab-paclitaxel was favorable.

Full data from the study will be presented at the 2025 ASCO Annual Meeting.

“Pancreatic cancer is one of the most aggressive and difficult-to-treat malignancies, where patients urgently need new therapeutic options,” Daniel Schmitt, president and chief executive officer of Actuate Therapeutics, stated in a news release. “There have been no major advances in improving survival in first-line treatment of metastatic pancreatic cancer in over a decade. Demonstrating statistically significant increases in both median OS and percent of patients reaching 1-year survival and beyond, along with a favorable risk-benefit profile in this phase 2 trial, further demonstrates elraglusib’s potential to shift the treatment paradigm in metastatic pancreatic ductal adenocarcinoma. We are incredibly excited to present the topline data at ASCO. Based on the significant improvement in survival we have seen to date in the combination arm, we look forward to working with United States and European Union regulators in the second half of this year to map out the path to advancing elraglusib to [a] new drug application and registration and making the drug available to patients as expeditiously as possible.”

Actuate-1801 was phase 1/2 study that evaluated elraglusib in patients with refractory cancers.2 The study included 3 parts:

• Part 1: dose escalation with elraglusib monotherapy to identify the maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D)
• Part 2: dose escalation with elraglusib plus standard anticancer agents to identify the MTD and RP2D
• Part 3: a randomized portion evaluating elraglusib plus gemcitabine and nab-paclitaxel vs chemotherapy alone in patients with previously untreated, locally advanced or metastatic pancreatic cancer.

In part 3, patients needed to be 18 years of age with at least 1 measurable lesion per RECIST 1.1 criteria. Other key inclusion criteria comprised adequate bone marrow, liver, and renal function; and an ECOG performance status of 0 to 1. Treatment with fluorouracil or gemcitabine in the adjuvant setting as a radiation sensitizer was allowed if given more than 6 months prior to enrollment. Neoadjuvant FOLFIRINOX was also allowed if the last dose was given at least 6 months before study entry.

Patients were excluded if they had endocrine or acinar pancreatic carcinoma; had significant cardiovascular impairment; experienced a myocardial infarction within 12 weeks of first study treatment; or had symptomatic, rapidly progressive brain metastases or leptomeningeal involvement. Notably, major surgery within 7 days of enrollment or plans to undergo major surgery during the study also precluded patients from enrollment.

In part 3B, patients (n = 286) were randomly assigned 2:1 to receive elraglusib at 9.3 mg/kg on day 1 of each week during 28-day cycles plus gemcitabine and nab-paclitaxel; or gemcitabine plus nab-paclitaxel alone.1

Along with the primary end point of OS, secondary end points included overall response rate, disease control rate, progression-free survival, and safety.

References

1. Actuate Therapeutics announces statistically significant topline results from global phase 2 trial of elraglusib in first-line treatment of metastatic pancreatic cancer. News release. Actuate Therapeutics. May 6, 2025. Accessed May 6, 2025. https://www.globenewswire.com/news-release/2025/05/06/3074989/0/en/Actuate-Therapeutics-Announces-Statistically-Significant-Topline-Results-from-Global-Phase-2-Trial-of-Elraglusib-in-First-Line-Treatment-of-Metastatic-Pancreatic-Cancer.html
2. 9-ING-41 in patients with advanced cancers. ClinicalTrials.gov. Updated November 7, 2024. Accessed May 6, 2025. https://clinicaltrials.gov/study/NCT03678883