1987TiP - Pembrolizumab in combination with eftilagimod alpha and radiotherapy in neoadjuvant treatment of patients with soft tissue sarcomas: EFTISARC-NEO trial

Background

Surgery is the mainstay of treatment of primary localized soft tissue sarcoma (STS). In patients (pts) with high grade localized STS of the extremity/trunk, and tumor size > 5cm radiation therapy (RT) is added to reduce local recurrence. While neoadjuvant chemotherapy is used to improve survival, but its efficacy is limited to pts with poor prognosis. Recently, immunotherapy (ITH) has been widely studied in pts with metastatic STS but response rates are modest and its efficacy and impact on the tumor microenvironment remain unclear. Novel compounds, such as eftilagimod alpha (efti), a soluble LAG-3 protein, are tested in combination with ITH to stimulate antigen presenting cells and boost immune response. Moreover, some studies have shown that combining ITH with RTH may be a promising strategy for synergistic enhancement of treatment efficacy. Therefore, we hypothesize that the addition of combined ITH to RT prior to surgical resection would be safe and improve pathologic response compared to historical cohorts of pts with localized STS treated with RT alone.

Trial design

EFTISARC-NEO is an open-label phase II study evaluating the efficacy and safety of pembrolizumab in combination with efti and RTH in the neoadjuvant treatment of pts with STS. Forty pts will be enrolled to receive efti 30 mg sc Q2W (5 cycles) and pembrolizumab 200 mg iv Q3W (3 cycles) with concurrent RT (25x2Gy), followed by surgery. Key eligibility criteria are: 1) primary or locally recurrent deep-seated extremity, girdles and/or superficial trunk tumor, 2) one of the following subtypes: undifferentiated pleomorphic sarcoma, myxofibrosarcoma, dedifferentiated liposarcoma, myxoid and round cell liposarcoma, epithelioid sarcoma, angiosarcoma, soft tissue sarcoma NOS; 3) Grade 2/3 according to FNCLCC; 4) primary tumor size >5 cm or locally recurrent of any size. The primary endpoint is a percent of tumor hyalinization at the time of surgical resection. Secondary endpoints include disease-free survival, overall survival, response rate and incidence of adverse events. Correlation between tissue or blood-based biomarkers and clinical outcomes will be explored. Enrollment for the study is ongoing in Poland.

Clinical trial identification

EudraCT 2022-003845-36.

Editorial acknowledgement

Legal entity responsible for the study

Maria Sklodowska-Curie National Research Institute of Oncology Warsaw Poland.

Funding

Financed by the Medical Research Agency from the state budget, agreement no 2022/ABM/01/00013 Eftilagimod alpha is provided by IMMUTEP Ltd.

Disclosure

K. Kozak: Financial Interests, Personal, Invited Speaker: BMS, MSD, Novartis, Pierre Fabre, Sanofi. P. Sobczuk: Financial Interests, Personal, Other, Travel grant: Novartis; Financial Interests, Personal, Other, Travel Grant: MSD, BMS; Financial Interests, Personal, Invited Speaker: Swixx BioPharma, BMS, Gilead; Financial Interests, Personal, Advisory Board: Sandoz; Financial Interests, Personal, Stocks/Shares: CelonPharma; Non-Financial Interests, Institutional, Product Samples: Immutep; Non-Financial Interests, Leadership Role, Board Member, Chair of Young Oncologists Section: Polish Society of Clinical Oncology. T. Switaj: Financial Interests, Personal, Invited Speaker: BMS, MSD, Novartis. P. Teterycz: Financial Interests, Personal, Other, travel grant: BMS, MSD. P. Rutkowski: Financial Interests, Personal, Invited Speaker, honoraria for lectures: MSD, BMS, Pierre Fabre; Financial Interests, Personal, Advisory Board: MSD, BMS, Pierre Fabre, Merck, Sanofi, Blueprint Medicines, Philogen; Financial Interests, Personal, Invited Speaker: Merck, Sanofi, Novartis, AstraZeneca; Financial Interests, Institutional, Research Grant, research grant for ISS: Pfizer; Financial Interests, Institutional, Funding, research grant for institution: BMS; Non-Financial Interests, Member of Board of Directors: Polish Society of Surgical Oncology; Non-Financial Interests, Member of Board of Directors, President: Polish Oncological Society. All other authors have declared no conflicts of interest.