Elraglusib nearly doubles 1-year survival rates in PDAC clinical trial
Actuate eyes regulatory path for treatment in advanced pancreatic cancer
Actuate Therapeutics’ treatment candidate elraglusib significantly lowered the risk of death — about doubling one-year survival rates — among people with an advanced form of pancreatic cancer called metastatic pancreatic ductal adenocarcinoma (PDAC).
That’s according to top-line findings from Part 3B of the Phase 1/2 Actuate-1801 trial (NCT03678883) that were recently presented at the American Society of Clinical Oncology (ASCO) annual meeting.
Expert clinicians discussing the data at a key opinion leader event indicated the treatment could fill a substantial unmet treatment need for people with advanced PDAC, where therapeutic innovation has been limited in recent years.
“The reception we received at ASCO confirms what we already believed — this data has the potential to change the trajectory of [metastatic] PDAC treatment,” Daniel Schmitt, Actuate’s president and CEO, said in a company press release. “We are now laser-focused on turning this promise into patient access.”
Based on elraglusib’s “clear survival benefit, favorable safety profile, and strong scientific rationale,” Schmitt indicated that Actuate plans to discuss a path toward regulatory approval with the U.S. Food and Drug Administration and the European Medicines Agency.
The CEO noted in a separate press release that such discussions are planned for the second half of this year. “We believe this enables us to move rapidly [toward] commercialization and delivery of this first-in-class therapy to patients with an urgent unmet need,” Schmitt said.
Treatment designed to block activity of protein that helps cancer cells survive
PDAC is the most common type of pancreatic cancer. It is often not diagnosed until the cancer has already become metastatic, meaning it has spread outside the pancreas and treatment options are more limited.
“Pancreatic cancer continues to represent one of the highest unmet medical needs with no major treatment advances in recent years … new mechanisms of action are urgently needed,” said Deva Mahalingam, MD, PhD, of Northwestern University’s Feinberg School of Medicine and principal investigator of the Actuate-1801 Part 3B trial.
Elraglusib is designed to block the activity of GSK-3 beta, a protein that helps cancer cells survive and resist chemotherapy. It’s expected to inhibit tumor growth through several mechanisms, including enhancing chemotherapy responses, activating anti-tumor immune activity, and regulating gene activity that influences tumor metabolism.
Actuate is evaluating the potential of elraglusib formulations in various forms of hard-to-treat cancer.
Part 3B of the Phase 2 trial enrolled 286 adults with metastatic PDAC who had not yet been treated. They received a standard chemotherapy combination of gemcitabine and nab-paclitaxel (GnP), either with or without elraglusib. Elraglusib was given via infusion into the bloodstream on the first day of each four-week treatment cycle.
One-year survival rates nearly doubled with elraglusib
As previously reported by Actuate, and consistent with earlier interim analyses, the top-line results show the addition of elraglusib to the treatment regimen had a significant survival benefit, meeting its main efficacy goal.
The median overall survival was increased significantly by nearly three months with elraglusib compared to GnP alone — 10.1 months vs. 7.2 months — amounting to a 37% lower risk of death.
After a year, 44.1% of people who received elraglusib were alive, which is about double what was observed in the GnP-only group, where 22.3% of participants were alive at the same timepoint.
This survival benefit with elraglusib versus standard chemotherapy alone was sustained out to 1.5 years (19.7% vs. 4.4%) and two years ( 13.8% vs. 0%).
The treatment combination also led to numerically higher overall response rates — the proportion of people who had at least a partial cancer shrinkage — compared to GnP only (29% vs. 21.8%).
The addition of elraglusib to the existing chemotherapy backbone of gemcitabine and nab-paclitaxel is promising and may represent a meaningful therapeutic advance for patients with pancreatic cancer.
Median progression-free survival, or the time spent alive without disease progression, was 5.6 months with elraglusib and 5.1 months without it. The median duration of the treatment response was 5.5 months with elraglusib and four months without it.
The side effect profile was similar between the two treatment arms. Most treatment-related side effects were mild or moderate in severity, with the most common being temporary and reversible visual impairments.
Biomarker analyses indicated lower blood levels of certain immune signaling molecules were correlated with better one-year survival.
Tumor biopsies showed elraglusib was associated with immune cell alterations consistent with its proposed immune modulating mechanisms in PDAC.
“The addition of elraglusib to the existing chemotherapy backbone of gemcitabine and nab-paclitaxel is promising and may represent a meaningful therapeutic advance for patients with pancreatic cancer,” Mahalingam said.
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