Immutep Limited has announced positive results from its EFTISARC-NEO Phase II clinical trial, demonstrating that eftilagimod alpha (efti) in combination with radiotherapy and Merck's KEYTRUDA® (pembrolizumab) successfully met the primary endpoint in patients with resectable soft tissue sarcoma (STS). The chemotherapy-free approach represents a significant advancement for treating this aggressive orphan cancer with limited therapeutic options.
Trial Results Exceed Expectations
The study, conducted at the Maria Skłodowska-Curie National Research Institute of Oncology in Warsaw, achieved a median tumor hyalinization and fibrosis rate of 50% in preliminary analysis. This result substantially exceeded the prespecified benchmark of 35% and demonstrated marked improvement over the 15% rate typically observed with radiotherapy alone.
Tumor hyalinization and fibrosis serve as key surrogate markers associated with improved survival outcomes in soft tissue sarcoma patients. The significant increase in these markers suggests the combination therapy effectively modulates the tumor microenvironment, which is characteristically immunosuppressive in STS.
Clinical Significance for Orphan Cancer
Principal investigators Dr. Katarzyna Kozak and Dr. Paweł Sobczuk emphasized the clinical importance of these findings. "This chemotherapy-free combination far exceeded the ambitious target we initially set," the investigators stated. "There remains a very high unmet need in this aggressive orphan cancer indication."
Soft tissue sarcoma represents a rare cancer with poor prognosis and limited treatment options. According to the American Cancer Society, approximately 13,520 new cases and 5,420 deaths from STS are estimated in the United States for 2025. The disease's rarity and aggressive nature have historically limited therapeutic development and patient outcomes.
Mechanism of Action and Immune Response
The combination therapy's success appears to stem from efti's mechanism of activating antigen-presenting cells and initiating a broad immune cascade. This approach effectively addresses the immunosuppressive tumor microenvironment characteristic of soft tissue sarcomas, potentially enabling enhanced immune recognition and response against cancer cells.
The strong anti-cancer response observed in the trial supports efti's classification as a first-in-class MHC Class II agonist, which has received Fast Track designation from the US FDA for use in non-small cell lung cancer and head and neck cancer when combined with anti-PD-1 therapies.
Broader Clinical Development Program
The EFTISARC-NEO trial represents one component of Immutep's comprehensive clinical program for eftilagimod alpha. The company is simultaneously evaluating efti across multiple solid tumor indications, including non-small cell lung cancer, metastatic breast cancer, and head and neck squamous cell carcinoma.
Full results from the 40-patient trial, which received partial funding from the Polish Medical Research Agency, are expected to be presented at a medical meeting later this year. These data will provide additional insights into the combination's efficacy profile and potential for broader clinical application.
Market Impact and Future Implications
The positive trial results position Immutep's efti combination as a potential paradigm shift in soft tissue sarcoma treatment, offering a chemotherapy-free alternative that may improve patient outcomes while reducing treatment-related toxicities. The success in this challenging indication may also support broader development across Immutep's pipeline of LAG-3-related immunotherapies.
As a late-stage biotechnology company specializing in novel immunotherapies for cancer and autoimmune diseases, Immutep continues to leverage its expertise in Lymphocyte Activation Gene-3 (LAG-3) research to advance innovative treatment options across multiple therapeutic areas.
