Breakthrough Clinical Results
Actuate Therapeutics announced positive topline Phase 2 data for elraglusib in combination with gemcitabine/nab-paclitaxel (GnP) in first-line metastatic pancreatic ductal adenocarcinoma (mPDAC). The Actuate-1801 Part 3B trial met its primary endpoint, showing a statistically significant improvement in median overall survival and 1-year survival rate compared to GnP alone. The data will be presented orally at the 2025 ASCO Annual Meeting. The combination therapy also demonstrated increased objective response rates (ORR) and disease control rates (DCR). Actuate will host a Key Opinion Leader (KOL) event to further discuss the results.
Key Highlights
- Statistically significant improvement in median overall survival and 1-year survival rate in first-line mPDAC patients treated with elraglusib + GnP compared to GnP alone.
- Positive results presented at the 2025 ASCO Annual Meeting.
- Increased objective response rates (ORR) and disease control rates (DCR) observed in the elraglusib/GnP combination arm.
- KOL event scheduled to review the data in detail.
Incidence and Prevalence
Latest Estimates of Incidence and Prevalence of Metastatic Pancreatic Cancer
Based on data from the SEER database, metastatic pancreatic cancer represents a significant portion of all pancreatic cancer diagnoses. Specifically, 52.31% of all diagnosed pancreatic cancer cases are metastatic, accounting for 6,775 out of 12,951 cases analyzed.
Between 2010 and 2013, a total of 13,233 patients with stage IV pancreatic cancer and known sites of distant metastases were identified in the SEER database. A more extensive SEER study covering the period from 1993 to 2013 identified 57,263 patients diagnosed with metastatic pancreatic cancer.
Demographic Characteristics
In the metastatic pancreatic cancer population: - 52% were male - The median age at diagnosis was 69 years (range: 15-104) - The most common age groups at diagnosis were:
-
Above 70 years: 39.39%
-
60-70 years: 38.02%
- The proportion of early-onset pancreatic cancer (EOPC) was only 2.84%
Anatomical Distribution
Compared to all stages of pancreatic cancer, metastatic cases show a different pattern of primary tumor location: - Lower proportion originating from the head of the pancreas (39.33% versus 50.63% for all stages) - Higher proportion originating from the tail (17.99% versus 13.39% for all stages)
Genetic Characteristics
- BRCA1/BRCA2 mutations occur in approximately 5% of metastatic pancreatic cancer patients in the general Caucasian population
- MSI-H metastatic pancreatic cancers have a frequency of about 1%
Survival Outcomes
- Median overall survival remained stable at 2 months between 1993 and 2013
- Patients with isolated liver metastases have worse outcomes compared to those with isolated lung or distant nodal metastases
- The percentage of patients surviving ≥12 months improved from 4.9% in 1993 to 12.7% in 2013
- The percentage of patients dying within 2 months decreased from 63.5% to 50.6% between 1993 and 2013
These statistics highlight the significant burden of metastatic pancreatic cancer globally and the modest improvements in survival outcomes over a 20-year period.
Economic Burden
Economic Burden of Treating Metastatic Pancreatic Cancer in the USA
A retrospective cohort study examined the economic burden of treating Stage IV pancreatic cancer patients in the USA, specifically focusing on Medicare payments and patient out-of-pocket costs during the last 30 days of life.
The study analyzed data from 3,825 patients aged 66 years or older who were diagnosed with Stage IV pancreatic cancer between 2006-2011, using linked Surveillance, Epidemiology, and End Results-Medicare data.
Key findings regarding economic burden and healthcare utilization include:
- Chemotherapy use was associated with a more than 50% increase in patient out-of-pocket costs for care ($1,311.5 vs. $841.0, p < 0.001) in the last 30 days of life
-
Patients receiving chemotherapy experienced:
-
Increased rates of hospital admissions (45.0% vs. 29.2%)
-
More frequent emergency department visits (41.3% vs. 27.2%)
-
Higher likelihood of death in a hospital (14.2% vs. 9.1%)
-
Fewer days in hospice care (11.5 days vs. 15.7 days)
Among patients who initiated chemotherapy, even more substantial differences in healthcare use and costs were observed depending on whether patients received chemotherapy in the last 30 days of life.
This data highlights the significant financial impact of chemotherapy treatment on patients with metastatic pancreatic cancer, as well as its influence on the pattern of healthcare utilization near the end of life.
Study Design Parameters
Key Trials for Metastatic Pancreatic Cancer: Study Design Parameters and Endpoints
Study 1: GEMPAX Trial
-
Design Parameters:
-
Open-label, randomized phase III clinical trial
-
211 patients (median age 64 years, 62% male)
-
Patients randomly assigned 2:1 to receive GEMPAX (paclitaxel 80 mg/m² + gemcitabine 1,000 mg/m²; IV; days 1, 8, 15) or gemcitabine alone (days 1, 8, 15) every 28 days
-
Endpoints:
-
Primary: Overall survival (OS)
-
Secondary: Progression-free survival (PFS), objective response rate (ORR), quality of life, and safety
-
Results: Median OS was 6.4 vs 5.9 months (HR 0.87, p=0.4095), median PFS was 3.1 vs 2.0 months (HR 0.64, p=0.0067), and ORR was 17.1% vs 4.2% (p=0.008) in GEMPAX vs gemcitabine alone
Study 2: Kobe University Hospital Study
-
Design Parameters:
-
Analysis of 99 consecutive patients with stage IV pancreatic cancer
-
Evaluated prognostic variables for survival including sex, age, performance status, tumor characteristics, treatments
-
Statistical analysis: Cox proportional hazards model
- Results: Multivariate analysis showed pancreatic resection, gemcitabine, and distant metastasis significantly influenced survival
Study 3: Phase 1b Trial of Afatinib with Gemcitabine/Nab-Paclitaxel
-
Design Parameters:
-
Treatment-naïve patients with histologically proven mPDAC and ECOG 0/1
-
Received gemcitabine/nab-paclitaxel with afatinib using a 3+3 design
-
Started at dose level 0 with gemcitabine/nab-paclitaxel 1000 mg/m²/125 mg/m² (days 1, 8, 15 of 28-day cycle) + oral afatinib 30 mg daily
-
Endpoints:
-
Primary: Maximum tolerated dose (MTD)
-
Results: MTD established at gemcitabine/nab-paclitaxel (1000 mg/m²/125 mg/m²) and afatinib (30 mg); ORR was 36.4%, median PFS was 3.5 months, median OS was 7.5 months
Study 4: National Cancer Database Retrospective Analysis
-
Design Parameters:
-
Analysis of 25,596 Stage IV pancreatic cancer cases (2014-2016)
-
Minimum 30-day follow-up
-
Statistical methods: Kaplan-Meier curves, Log-rank tests, multivariable Cox models, propensity score matching
- Results: Immunotherapy (n=163) was associated with improved OS (median 12.2 vs 5.8 months, p<0.0001); 12 and 24-month survival of 51.0% and 20.0% vs 28.2% and 11.9% in non-immunotherapy group
Study 5: SEER Database Analysis
-
Design Parameters:
-
13,233 patients with stage IV pancreatic cancer (2010-2013)
-
Focus on site-specific metastases
-
Statistical methods: Chi-square test, Kaplan-Meier analysis, log-rank testing, Cox proportional model
- Results: Patients with isolated distant nodal involvement or lung metastases had better overall and pancreatic cancer-specific survival compared to patients with isolated liver metastases
Drug used in other indications
Based on the context provided, there is no information available about elraglusib and gemcitabine/nab-paclitaxel being trialed for indications other than metastatic pancreatic cancer. Additionally, no information is provided about the intervention models for any trials involving elraglusib.
The context mentions other treatment combinations being studied for pancreatic cancer, including: - Afatinib with gemcitabine/nab-paclitaxel - Napabucasin with nab-paclitaxel and gemcitabine - Sintilimab (PD-1 inhibitor) with Nab-paclitaxel plus S1 - Bevacizumab with gemcitabine - Gemcitabine plus erlotinib
However, none of these mentions relate to elraglusib specifically, and the context does not contain information about intervention models for these alternative treatment combinations.