Elraglusib can prolong survival in metastatic pancreatic cancer: Trial
'Highly encouraging' interim results from Phase 1/2 clinical trial
Adding elraglusib, a small molecule being developed by Actuate Therapeutics, to standard chemotherapy with gemcitabine and nab-paclitaxel (GnP) as a first-line treatment for metastatic pancreatic cancer can prolong survival over chemotherapy alone.
That’s according to interim data from the randomized part of Actuate-1801 (NCT03678883), a Phase 1/2 clinical trial that’s testing how well elraglusib works when given by intravenous (into-the-vein) infusion in addition to GnP in patients who have not received prior treatment.
“These interim results are highly encouraging and underscore the transformative potential of elraglusib in the treatment of metastatic pancreatic cancer,” Daniel Schmitt, Actuate’s president and CEO, said in a company press release.
Top-line trial data expected in first half of 2025
Top-line data from the ongoing trial, expected in the first half of 2025, may jumpstart elraglusib into the next phase of clinical testing. Last year, the U.S. Food and Drug Administration (FDA) granted elraglusib orphan drug designation for pancreatic cancer, a designation that comes with incentives to speed its development.
“We are excited to continue evaluating the potential of elraglusib,” Schmitt said, “and look forward to engaging with the FDA in [the first half of] 2025 to share topline data and discuss next steps, including a proposed Phase 3 registration trial.”
Pancreatic cancer forms in tissues of the pancreas and can be difficult to diagnose and treat. If it’s found early and hasn’t spread, it may be possible to remove the cancer with surgery, but if it has spread to other parts of the body (metastatic), other treatment strategies are necessary. Chemotherapy can be used to control symptoms, but some cancer cells grow resistant to it, causing it to fail.
Elraglusib, also called 9-ING-41, is designed to inhibit an enzyme called GSK-3, stopping it from working. GSK-3 helps cancer cells to grow and survive and to become resistant to chemotherapy. Preclinical data showed elraglusib can improve response in cancers that were previously resistant to treatment.
These interim results are highly encouraging and underscore the transformative potential of elraglusib in the treatment of metastatic pancreatic cancer.
The Actuate-1801 trial is divided into three parts. Part 1 tested if elraglusib was safe when given on its own at increasing doses, twice weekly, to 67 patients with metastatic cancer and found the best dose to use in the next step. Elraglusib was found to have a good safety profile.
Part 2 added elraglusib to chemotherapy to test for safety and find the best dose for use in Part 3. Part 2 included 171 patients with different types of advanced cancers, 58 (33.9%) with pancreatic cancer, and the initial recommended dose was 15 mg/kg twice weekly.
In Part 3, researchers tested how well elraglusib works when given in combination with GnP to treat pancreatic ductal adenocarcinoma, the most common form of pancreatic cancer. Of 42 patients, 38 received elraglusib at 15 mg/kg and four at a lower dose of 9.3 mg/kg.
More than half of the patients (51.7%) achieved disease control, defined as stable disease for at least 16 weeks, or about four months, leading the researchers to run Part 3B, where they’re watching for changes in one-year survival in patients treated with elraglusib, at a dose of 9.3 mg/kg once weekly, in combination with GnP.
Combination therapy improved 1-year survival rate
Interim data showed the combination of elraglusib with GnP improved the one-year survival rate compared with GnP alone (43.6% vs. 22.5%). Longer-term benefits were observed, with 18-month and 24-month survival rates of 20.9% and 16.7%, respectively, compared with 0% at both time points for patients treated with GnP.
As of the Nov. 15 data cutoff date, 38% of patients in the elraglusib plus GnP arm were alive, compared to 19% in the GnP group.
The combination reduced the risk of death by 37% and increased median overall survival to 9.3 months versus 7.2 months. Progression-free survival was longer (5.6 vs. 4.9 months) and the disease control rate (42.6% vs. 33.3%) and objective response rate (27.7% vs. 20.5%) were also higher.
Progression-free survival refers to the time a person lives without the disease advancing, while disease control rate reflects the proportion of patients experiencing a response to treatment, and the objective response rate reflects the percentage of patients who have a partial or complete response to treatment.
Two patients in the combination group had tumors reduced enough for surgery, with one patient achieving complete removal. The combination group also had one complete response and one partial response, compared with none for patients treated with GnP alone.
Side effects reported for the combination of elraglusib with GnP were similar to those observed with GnP alone, indicating a favorable risk-benefit profile.
Andrew Mazar, PhD, Actuate’s chief operating officer, said that with “the favorable risk-benefit profile observed to date,” elraglusib “may provide a treatment option for many patients with metastatic pancreatic cancer that may not tolerate more aggressive and less tolerable chemotherapy approaches.”
About the Author
