Immutep Limited has announced encouraging initial data from its EFTISARC-NEO Phase II trial, demonstrating that a novel triple combination therapy achieved near-complete pathologic responses in 67% of soft tissue sarcoma patients. The investigator-initiated trial combines eftilagimod alpha (efti) with radiotherapy and KEYTRUDA® (pembrolizumab) in a neoadjuvant setting.
Strong Pathologic Response Rates
The trial's initial efficacy data revealed that 4 of 6 patients (67%) achieved near-complete responses according to EORTC-STBSDG criteria, which measures responses via tissue pathology after surgery. These deep responses are rarely observed in soft tissue sarcoma patients receiving standard therapeutic approaches including radiotherapy.
"The initial pathologic responses from this novel combination are very encouraging and supportive of the potential synergistic effects of this new therapeutic approach," stated Katarzyna Kozak, M.D., Ph.D., and Paweł Sobczuk, M.D., Ph.D., medical oncologists at the Department of Soft Tissue/Bone Sarcoma and Melanoma at MSCNRIO (Warsaw) and the trial's principal investigators. "Indeed we have seen a high degree of hyalinization/fibrosis in the surgical samples which we rarely see with standard treatments."
Novel Mechanism and Safety Profile
The EFTISARC-NEO study represents the first evaluation of efti in a neoadjuvant setting and the first combination with radiotherapy. The triple combination revealed no new safety findings and was well tolerated in the first six patients who completed 10 weeks of treatment followed by surgery 2-3 weeks later.
Efti functions as an MHC Class II agonist that targets and uniquely activates dendritic cells, the most potent professional antigen-presenting cells. This mechanism leads to broad adaptive and innate immunity to fight cancer, including proliferation of CD8+ cytotoxic T cells that can be armed with radiotherapy-induced tumor antigens.
Addressing Unmet Medical Need
Soft tissue sarcoma represents a significant unmet medical need as an orphan disease with poor prognosis. The incidence varies by region, with approximately 23,400 cases annually and a crude incidence of 4.7 per 100,000 in Europe, according to the RARECARE project. In the United States, an estimated 13,400 new cases occur annually with 5,140 deaths, according to the American Cancer Society.
"We are pleased to see these early results from EFTISARC-NEO, which has allowed efti for the first time to be clinically evaluated in a non-metastatic cancer setting," said Frédéric Triebel, M.D., Ph.D, Immutep's Chief Scientific Officer. "If the positive trend of strong pathological responses continues in this rare orphan disease, we will pursue all available avenues to bring this innovative therapy to soft tissue sarcoma patients in need of new, effective therapies in an expeditious manner."
Trial Design and Future Plans
The open-label EFTISARC-NEO Phase II study will treat up to 40 patients and is being conducted by the Maria Skłodowska-Curie National Research Institute of Oncology (MSCNRIO) in Warsaw. The trial is primarily funded with an approved grant from the Polish government awarded by the Polish Medical Research Agency program.
The study's primary endpoint is the pathologic response rate, defined as percentage of tumor hyalinization/fibrosis assessed at the time of surgical resection. The effectiveness is determined by the lower number of viable tumor cells and higher extent of hyalinization/fibrosis observed in patients' tumor specimens.
The trial is ongoing with 14 patients now enrolled, and additional clinical data is planned for presentation at a medical conference in the second half of 2024.
