Journal: Nature medicine
Study type and population
- Open-label, international, multicenter phase 2 trial.
- Population: Previously untreated metastatic pancreatic ductal adenocarcinoma.
- Randomization: 2:1 to elraglusib + gemcitabine/nab-paclitaxel (GnP) vs GnP alone.
- Modified intention-to-treat: 155 on elraglusib/GnP, 78 on GnP.
Efficacy
- Median overall survival:
- Elraglusib/GnP: 10.1 months
- GnP: 7.2 months
- Hazard ratio for death: 0.62 (95% CI 0.46–0.84; P = 0.01), ≈38% relative risk reduction.
- 1‑year overall survival rate:
- Elraglusib/GnP: 44.1%
- GnP: 22.3%.
Safety
- Overall safety profile: described as manageable.
- Most common grade ≥3 treatment-emergent AEs (elraglusib/GnP vs GnP):
- Neutropenia: 52.3% vs 30.8%
- Anemia: 25.2% vs 29.5%
- Fatigue: 16.8% vs 5.1%.
Correlative/biologic findings
- Baseline circulating immune-related factors (notably CXCL2 and TRAIL ligands) correlated with better survival in the elraglusib/GnP arm.
- Treatment-associated changes: increased intratumoral cytotoxic immune cell populations, consistent with an immune-modulatory/antitumor mechanism for GSK-3β inhibition.
Clinical implication
- Adding elraglusib to standard GnP in first-line mPDAC improved survival with acceptable toxicity, and the biologic correlatives provide a mechanistic rationale.
- Future direction: Results support further evaluation; a phase 3 trial is planned.