EFTISARC-NEO Trial Meets Primary End Point in Soft Tissue Sarcoma
The EFTISARC-NEO trial of eftilagimod alfa with radiotherapy and pembrolizumab in resectable soft tissue sarcoma achieved its primary end point.
Sarcoma cells: Developing in connective tissues like bones and muscles, these spindle-shaped cells are known for their aggressiveness and rapid spread: © BEST - stock.adobe.com
The phase 2 EFTISARC-NEO trial (NCT06128863) evaluating eftilagimod alfa (IMP321) with radiotherapy plus pembrolizumab (Keytruda) as neoadjuvant therapy for resectable soft tissue sarcoma met its primary end point of tumor hyalinization/fibrosis, an early surrogate end point associated with improved overall survival (OS) and recurrence-free survival (RFS).1
“It is very encouraging to see the chemotherapy-free combination with efti[lagimod alfa] far exceed the ambitious target we initially set for the trial's primary [end point] in resectable soft tissue sarcoma. These results support our belief that [efti]lagimod alfa['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 anticancer efficacy,” said Katarzyna Kozak, MD, PhD, and Paweł Sobczuk, MD, PhD, medical oncologists at the Department of Soft Tissue/Bone Sarcoma and Melanoma at MSCNRIO and principal investigators of EFTISARC-NEO, in a press release.
The combination significantly exceeded the study’s prespecified median of 35% tumor hyalinization/fibrosis vs the historical 15% from radiotherapy alone in this patient population. Full data will be presented at a future medical meeting.
“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,” added Kozak and Sobczuk in the press release.
Data from a preliminary analysis of 21 patients presented at the Connective Tissue Oncology Society Annual Meeting in November 2024 showed that the combination of eftilagimod alfa, radiotherapy, and pembrolizumab demonstrated significant efficacy and led to a median of 50% tumor hyalinization/fibrosis. Following this, EFTISARC-NEO completed enrollment in January 2025 with 40 patients.
About EFTISARC-NEO
The phase 2, single-arm, single-stage EFTISARC-NEO study is investigating the soluble LAG-3 protein eftilagimod alfa administered concurrently with pembrolizumab and radiotherapy.2 Systemic therapy is 9 weeks long from weeks 1 to 9, and radiotherapy is 5 weeks long from weeks 2 to 6, and surgery is completed in weeks 11 to 12.
The study’s primary end point is pathologic response as assessed by tumor hyalinization/fibrosis, and secondary end points include incidence of adverse events, number of patients completing neoadjuvant therapy, disease-free survival, local RFS, distant metastasis-free survival, OS, and response rate.
To be eligible for study participation, patients were required to have primary or locally recurrent soft tissue sarcoma in deep-seated extremities, girdles, or superficial trunk regions of the body; grade 2 or 3 tumors according to Fédération Nationale des Centres de Lutte contre le Cancer; nonmetastatic disease; and measurable disease per RECIST 1.1. Those with Ewing, alveolar, or embryonal rhabdomyosarcoma or who have previously received eftilagimod alfa, anti-PD-(L)1 agents, or radiotherapy were not eligible for study enrollment.
The estimated study completion date is April 30, 2027.
