Neoadjuvant Efti/Keytruda Combo Improves Tumor Fibrosis Rates in Sarcoma

Neoadjuvant efti and Keytruda plus radiotherapy met the EFTISARC-NEO trial's primary end point insoft tissue sarcoma: © stock.adobe.com.

Neoadjuvant treatment with eftilagimod alfa (IMP321; efti) and Keytruda (pembrolizumab) plus radiotherapy significantly improved tumor hyalinization/fibrosis rates compared with radiotherapy alone in patients with resectable soft tissue sarcoma, meeting the phase 2 EFTISARC-NEO trial's primary end point, according to a news release from Immutep.

Specifically, the combination significantly exceeded the study’s prespecified median tumor hyalinization/fibrosis rate of 35%, higher than the 15% rate seen with historical data of radiotherapy alone in patients with resectable soft tissue sarcomas

“It is very encouraging to see the chemotherapy-free combination with efti far exceed the ambitious target we initially set for the trial's primary endpoint in resectable soft tissue sarcoma,” Drs. Katarzyna Kozak and Paweł Sobczuk said in the news release.

“These results support our belief that efti's activation of antigen-presenting cells, and in turn a broad adaptive and innate immune response, helps transform the immunosuppressed tumor microenvironment of soft tissue sarcomas leading to strong anti-cancer efficacy. There remains a very high unmet need in this aggressive orphan cancer indication, and we look forward to presenting detailed results at a medical meeting later this year,” they continued.

Both Kozak and Sobczuk are medical oncologists in the Department of Soft Tissue/Bone Sarcoma and Melanoma at the Maria Skłodowska-Curie National Research Institute of Oncology (MSCNRIO) in Warsaw, the national reference center for soft tissue sarcoma in Poland.

Previous Findings and Current Evaluation of the Combination Therapy

Previously, investigators shared data on the combination at the Connective Tissue Oncology Society Annual Meeting in November 2024. The triplet therapy combination showed early results in patients with resectable soft tissue sarcoma, with a 50% median tumor hyalinization/fibrosis rate seen in a preliminary analysis of 21 patients.

The EFTISARC-NEO study completed enrollment of 40 patients in January 2025.

In a 2024 news release from Immutep, Kozak stated, “The initial pathologic responses from this novel combination are very encouraging and supportive of the potential synergistic effects of this new therapeutic approach. Indeed, we have seen a high degree of hyalinization/fibrosis in the surgical samples which we rarely see with standard treatments. We look forward to continuing this study.”

Efti is being studied across several solid tumor types, including non-small cell lung cancer, head and neck squamous cell carcinoma, and metastatic breast cancer. Its favorable safety profile supports its use in combination with anti–PD-1 or PD-L1 immunotherapy and chemotherapy. The Food and Drug Administration has granted efti fast track designation for first-line treatment of both head and neck squamous cell carcinoma and non-small cell lung cancer.

What is Tumor Hyalinization/Fibrosis in Soft Tissue Sarcoma?

Tumor fibrosis, or hyalinization, seen during surgery may serve as an early marker of treatment response and has been linked to longer survival and delayed recurrence in patients with soft tissue sarcoma. Investigators from the MSCNRIO plan to present full study findings at an upcoming medical meeting.

According to the release, soft tissue sarcoma is a rare disease with limited treatment options and poor outcomes for many patients. Incidence rates vary worldwide. In the United States, approximately 13,520 new cases and 5,420 deaths are expected in 2025, according to estimates from the American Cancer Society.

What is Efti and how Does it Work?

Efti is a novel immunotherapy designed to strengthen both arms of the immune system by activating antigen-presenting cells. As a first-in-class MHC class 2 agonist, it binds to MHC class 2 molecules on antigen-presenting cells, triggering a broad immune response that includes the activation of CD8+ T cells, CD4+ T cells, dendritic cells, natural killer cells and monocytes. This cascade also increases production of immune-stimulating molecules like interferon gamma and CXCL10, further enhancing the immune system’s ability to target and control cancer.

For more news on cancer updates, research and education, don’t forget to subscribe to CURE®’s newsletters here.