Eftilagimod Alfa/Radiotherapy/Pembrolizumab Yields Favorable Hyalinization/Fibrosis in Soft Tissue Sarcoma

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Neoadjuvant eftilagimod alfa (IMP321) in combination with radiotherapy and pembrolizumab (Keytruda) improved tumor hyalinization/fibrosis rates vs historical data with radiotherapy alone in patients with resectable soft tissue sarcoma, meeting the primary end point of the phase 2 EFTISARC-NEO trial (EudraCT 2022-003845-36).1

The combination exceeded the trial’s prespecified median tumor hyalinization/fibrosis rate of 35%, which was also higher than the 15% rate seen in historical data with radiotherapy alone in this patient population.

“It is very encouraging to see the chemotherapy-free combination with eftilagimod alfa far exceed the ambitious target we initially set for the trial's primary end point in resectable soft tissue sarcoma,” Katarzyna Kozak, MD, PhD, and Paweł Sobczuk, MD, PhD, medical oncologists in the Department of Soft Tissue/Bone Sarcoma and Melanoma at the Maria Skłodowska-Curie National Research Institute of Oncology in Warsaw, Poland, as well as the trial’s principal investigators, stated in a news release. “These results support our belief that eftilagimod alfa’s activation of antigen-presenting cells, and in turn a broad adaptive and innate immune response, helps transform the immunosuppressed tumour microenvironment of soft tissue sarcomas leading to strong anticancer 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.”

Notably, tumor hyalinization/fibrosis is an early surrogate end point measured at the time of surgical resection that has been associated with overall survival (OS) and recurrence-free survival benefits for patients with soft tissue sarcoma.

The single-arm, single-center EFTISARC-NEO trial enrolled patients at least 18 years of age with an ECOG performance status of 0 or 1; tumors in the primary or locally recurrent deep-seated extremities, girdles, and/or superficial trunk; a histologic diagnosis of undifferentiated pleomorphic sarcoma, myxofibrosarcoma, dedifferentiated liposarcoma, myxoid and round cell liposarcoma, epithelioid sarcoma, angiosarcoma, or soft tissue sarcoma not otherwise specified; grade 2 or 3 tumors per FNCLCC criteria; primary tumors greater than 5 cm or locally recurrent tumors of any size; no distant metastases; no prior exposure to eftilagimod alfa or anti–PD-1/PD-L1 therapy; and no prior radiotherapy to tumor-involved sites.2

Key secondary end points included the incidence of adverse effects, disease-free survival (DFS), locoregional DFS, distant metastasis–free survival, OS, and radiologic response to neoadjuvant treatment per RECIST 1.1 criteria.

Data previously presented at the 2024 Connective Tissue Oncology Society Annual Meeting in November 2024 showed that in a preliminary analysis of 21 patients with resectable soft tissue sarcoma who were available for primary end point assessment, neoadjuvant treatment with eftilagimod alfa plus radiotherapy and pembrolizumab generated a median tumor hyalinization/fibrosis rate of 50% (IQR, 23.0%-82.0%). This translated to a greater than 3-fold increase in this rate.

Additionally, patients had a median of 8% (IQR, 3.5%-22.0%) of viable tumor cells in surgical specimens following treatment.

At a data cutoff date of October 20, 2024, the trial also demonstrated that 71.4% of patients achieved a pathologic response, defined as at least 35% tumor hyalinization/fibrosis; the pathologic complete response rate was 9.5%. Responders achieved pathological response per EORTC STBSG criteria of grades A (9.5%), B (9.5%), C (33.3%), D (38.1%), and E (9.5%). Furthermore, the objective response rate per RECIST 1.1 criteria was 19.0%.

The trial investigators noted that the triplet regimen appears to be safe. No grade 3 or higher toxicities were related to eftilagimod alfa or pembrolizumab.

Subsequently, in January 2025, the trial completed its target enrollment of 40 patients.

References

1. Immutep’s efti with radiotherapy & KEYTRUDA (pembrolizumab) meets primary endpoint in phase II for soft tissue sarcoma. News release. Immutep Limited. May 27, 2025. Accessed May 27, 2025. https://www.globenewswire.com/news-release/2025/05/27/3088523/0/en/Immutep-s-Efti-with-Radiotherapy-KEYTRUDA-pembrolizumab-Meets-Primary-Endpoint-in-Phase-II-for-Soft-Tissue-Sarcoma.html
2. Sobczuk P, Rogala P, Mariuk-Jarema A, et al. Preliminary results from a phase 2 EFTISARC-NEO trial of neoadjuvant soluble LAG-3 protein eftilagimod alpha, pembrolizumab, and concurrent radiotherapy in patients with resectable soft tissue sarcoma. Presented at: 2024 Connective Tissue Oncology Society Annual Meeting. November 13-16, 2024. San Diego, CA