Pembrolizumab in Combination With Eftilagimod Alpha and Radiotherapy in Neoadjuvant Treatment of Patients With Soft Tissue Sarcoma - EFTISARC-NEO Trial

Phase II, Single-arm Clinical Trial Evaluating Efficacy and Safety of Pembrolizumab in Combination With a Soluble LAG-3 Protein, Eftilagimod Alpha, and Radiotherapy in Neoadjuvant Treatment of Patients With Soft Tissue Sarcomas (EFTISARC-NEO)

This is a phase II single-arm single-stage study evaluating efficacy and safety of pembrolizumab in combination with a soluble LAG-3 protein, eftilagimod alfa (Efti) and radiotherapy in neoadjuvant treatment of patients with soft tissue sarcomas. This study will determine the pathologic response rate (defined as percentage of tumor hyalinization/fibrosis) to the combination treatment.

Systemic therapy with pembrolizumab and eftilagimod alfa and radiotherapy are administered concurrently. Systemic treatment lasts for 9 weeks (study week 1-9). Radiation therapy lasts for 5 weeks (5 days per week) in weeks 2-6. Surgery takes place 5-6 weeks after completion of radiation therapy (week 11-12). Any adjuvant treatment (chemotherapy, immunotherapy, radiation therapy) after surgical treatment is not allowed. Patients will be then followed up regularly for a period of 24 months.

Inclusion Criteria:

• Primary or locally recurrent deep-seated extremities, girdles and/or superficial trunk (thoracic or abdominal wall) soft tissue sarcoma
• Grade 2 or 3 tumors according to Fédération Nationale des Centres de Lutte contre le Cancer (FNCLCC);
• Size of the primary tumor >5 cm at instrumental staging (CT, MRI), or locally recurrent of any size;
• Measurable disease based on RECIST 1.1;
• Non-metastatic disease;

Exclusion Criteria:

• Ewing sarcoma, Alveolar and embryonal rhabdomyosarcoma
• Previous treatment with eftilagimod alfa, anti-PD-1 or anti-PD-L1;
• Prior radiotherapy to tumor-involved sites;