Elraglusib Combo Improves Survival in First-Line mPDAC
3D illustration of pancreas anatomy: ©rasi - stock.adobe.com
The combination of elraglusib (9-ING-41), a potent small molecule inhibitor of GSK-3β, and gemcitabine and nab-paclitaxel (Abraxane) achieved statistical significance when used for the first-line treatment of metastatic pancreatic ductal adenocarcinoma (mPDAC), according to topline results from part 3B of the ongoing phase 2 Actuate-1801 trial (NCT03678883).1
Specifically, the combination led to a statistically significant improvement in overall survival (OS) vs chemotherapy alone and confirming a significant 1-year survival rate. In addition, the risk/benefit profile of elraglusib in combination with gemcitabine and nab-paclitaxel was favorable.
With this, the study has met its primary end points, and additional findings will be presented in an oral presentation at the upcoming American Society of Clinical Oncology (ASCO) Annual Meeting.
“Pancreatic cancer is one of the most aggressive and difficult-to-treat malignancies, where patients urgently need new therapeutic options,” said Daniel Schmitt, president and chief executive officer of Actuate Therapeutics, in a press 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,” he continued.
About the Actuate-1801 Trial
Actuate-1801 is a phase 1/2 clinical trial designed to evaluate the safety and efficacy of elraglusib in patients with refractory cancers. The study was conducted in 3 sequential parts.2
Initially, in part 1, the trial focused on dose escalation using elraglusib monotherapy in order to determine the maximum tolerated dose (MTD) and establish the recommended phase 2 dose (RP2D) of the agent. This was followed by part 2, which involved dose escalation of elraglusib in combination with standard anticancer agents to similarly identify the MTD and RP2D for the combination regimen. Finally, part 3 consisted of a randomized evaluation of elraglusib in combination with gemcitabine and nab-paclitaxel compared to chemotherapy alone in patients with previously untreated, locally advanced or metastatic pancreatic cancer.
Eligibility criteria for patients in part 3 of the trial required that they be at least 18 years of age and have at least 1 measurable lesion according to RECIST 1.1 criteria. Additional inclusion criteria included adequate bone marrow, liver, and renal function, as well as an ECOG performance status of 0 or 1.
Prior treatment with fluorouracil or gemcitabine in the adjuvant setting was permitted if used as a radiation sensitizer more than 6 months prior to enrollment. Patients who had received neoadjuvant FOLFIRINOX were also eligible, provided that at least 6 months had passed since the last dose before entering the study.
In part 3B of the study, a total of 286 patients were randomly assigned in a 2:1 ratio to receive either elraglusib at a dose of 9.3 mg/kg administered on day 1 of each week in 28-day cycles in combination with gemcitabine and nab-paclitaxel, or gemcitabine and nab-paclitaxel alone.
The primary end point of this portion of the study was OS, with secondary end points including overall response rate (ORR), disease control rate (DCR), progression-free survival, and safety.
In August 2023, the FDA granted elraglusib an orphan drug designation for treatment of patients with pancreatic cancer, based on findings from the study.3 Findings showed that among the 21 patients in the study who were evaluable for response, the DCR was 62% and the ORR was 43%, with 2 confirmed complete responses, 6 confirmed and 1 unconfirmed partial response, 4 patients with stable disease, and 8 with disease progression.4 However, adverse events related to chemotherapy were significant.
