At ESMO 2025, Katarzyna Kozak presented EFTISARC-NEO, a single-arm, neoadjuvant phase II study, during the Proffered Paper session—Sarcoma, detailing how the combination of eftilagimod alpha (efti), a soluble LAG-3 agonist, and pembrolizumab, given concurrently with preoperative radiotherapy, may intensify tumor regression prior to surgery in patients with resectable, high-risk soft-tissue sarcoma.
Background
Perioperative radiotherapy (RT) is a cornerstone for stage III localized soft tissue sarcoma (STS), yet long-term outcomes remain suboptimal. Combining RT with immunotherapy could amplify antigen presentation and T-cell priming. Eftilagimod alpha (efti) activates antigen-presenting cells via LAG-3, providing a biologic rationale to pair it with anti–PD-1 therapy and RT to improve pathologic response and, potentially, disease control.
Methods
This single-arm, phase II trial enrolled patients with grade 2/3, stage III STS of the extremities or trunk. Treatment comprised efti 30 mg SC every 2 weeks ×5 and pembrolizumab 200 mg IV every 3 weeks ×3, delivered concurrently with RT (25×2 Gy), followed by surgery.
Primary endpoint: percentage of tumor hyalinization and fibrosis (designed to detect an improvement from 15% to 35%, two-sided α=0.05, power 90%).
Key secondary endpoints: DFS, OS, RECIST response, and adverse events (AEs).
Results
From July 2023 to January 2025, 40 patients were enrolled (median age 54.5 years [IQR 46.8–65.2]; median tumor size 8.8 cm [IQR 6.7–10.9]; 40% grade 3). Common subtypes: myxofibrosarcoma 37.5%, undifferentiated pleomorphic sarcoma 30%, myxoid liposarcoma 12.5%. Among 38 evaluable patients:
- Primary endpoint met: median hyalinization/fibrosis 51.5% (IQR 15–76; p<0.001).
- Viable tumor: median 12.5% (IQR 4.5–30).
- EORTC-STBSG pathologic response: 5.3% response A (complete), 5.3% response B, and 34.2% response C.
- RECIST 1.1: 13.2% partial response, 73.7% stable disease, 7.9% progression.
Safety
Treatment-related AEs occurred in 92.5%; grade 3–4 TRAEs in 20.0% (including 17.5% surgical grade 3/4 complications). Most frequent TRAEs (any grade): wound infection 38%, injection-site pain 35%, radiation dermatitis 35%, hypothyroidism 18%. No unexpected safety signals were reported.
Conclusions
The regimen achieved its primary endpoint, showing substantial tumor hyalinization/fibrosis and low residual viable tumor after neoadjuvant efti + pembrolizumab + RT, with a manageable safety profile. These data support advancing to late-phase trials to test whether enhanced pathologic response translates into improved DFS/OS in resectable, high-risk STS treated with perioperative radiotherapy.
You can read the full abstract here.