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

Study Overview
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Brief Summary
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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 alpha (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.

Detailed Description
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Systemic therapy with pembrolizumab and eftilagimod alpha 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.

Official Title
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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)

Conditions
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Neoadjuvant, Immunotherapy, Sarcoma,Soft Tissue, Radiation Therapy

Intervention / Treatment
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* Drug: Pembrolizumab, Eftilagimod alpha


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Primary or locally recurrent deep-seated extremities, girdles and/or superficial trunk (thoracic or abdominal wall) tumor; One of the following histologies as defined in the World Health Organization (WHO) Classification of Soft Tissue Tumors: undifferentiated pleomorphic sarcoma (UPS), myxofibrosarcoma, dedifferentiated liposarcoma (DDLPS), myxoid and round cell liposarcoma (MRCLPS), epithelioid sarcoma (ES), angiosarcoma (AS) soft tissue sarcoma not otherwise specified (NOS). 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: Previous treatment with eftilagimod alpha, anti-PD-1 or anti-PD-L1; Prior radiotherapy to tumor-involved sites;

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: single arm<br>Systemic therapy with pembrolizumab and eftilagimod alpha is given concurrently with radiotherapy. Surgery is scheduled 5-6 weeks after completion of radiotherapy. | Drug: Pembrolizumab, Eftilagimod alpha<br>* Eftilagimod alpha 20 mg s.c. every 2 weeks (5 doses), Pembrolizumab 200 mg i.v. every 3 weeks (3 cycles), Radiotherapy 50 Gy (25 x 2 Gy)<br>* Other names: Keytruda;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pathologic response | The primary efficacy endpoint is a percent tumor hyalinization as a marker of response to treatment assessed at the time of surgical resection. | At the time of definitive surgical treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants Experiencing Adverse Events (AEs) | Safety analyses will include all patients who received at least one dose of study drug. Safety will be assessed through summaries of adverse events, changes in laboratory test results, changes in vital signs. Verbatim description of adverse events will be summarized and graded according to International Common Terminology Criteria for Adverse Events (CTCAE), version 5.0. In addition, serious adverse events, severe adverse events (Grades 3, 4, and 5), and adverse events leading to study drug discontinuation or interruption will be summarized accordingly. | All adverse events will be documented from the enrolment of the first patient until 100 days after the surgical treatment of the last patient (2 years). | 
| Number of participants completing neoadjuvant therapy | Number of patients completing neoadjuvant treatment and having a curative surgery according to the protocol | 2 years | 
| Disease-free survival (DFS) | Disease-free survival (DFS) is defined as the time from between the date of curative surgery and the date of disease recurrence defined as clinically diagnosed or biopsy-confirmed recurrent sarcoma at a site of the primary tumor, development of nodal metastasis, locoregional recurrence or distant metastases confirmed by imaging or clinical examination, or death without documented recurrence | From the date of curative surgery to the date of first recurrence or death (whatever the cause), whichever occurs first | 
| Local recurrence-free survival (LRFS) | Local recurrence-free survival (LRFS) is defined as the time between the date of curative surgery and the date of local recurrence confirmed by imaging or clinical examination. Patients still alive and without signs of disease recurrence at the analysis cut-off date are censored at the last date known to be alive. | From the date of curative surgery to the date of first local recurrence or date of death (whatever the cause), whichever occurs first | 
| Distant metastasis-free survival (DMFS) | Distant metastasis-free survival (DMFS) is defined as the time between the date of curative surgery to the date of diagnosis of distant metastases confirmed by imaging or clinical examination. Patients still alive and without signs of distant metastases at the analysis cut-off date are censored at the last date known to be alive. | From the date of curative surgery to the date of first distant metastasis or date of death (whatever the cause), whichever occurs first | 
| Overall survival (OS) | Overall survival (OS) is defined as the time between the date of curative surgery and the date of death from any cause. For those without documentation of death, OS will be censored on the last date the participant was known to be alive. | From the date of curative surgery up to the date of death or the last date the participant was known to be alive | 
| Response rate | Radiologic Response To Neoadjuvant Treatment using RECIST 1.1 | From the date of the first dose of treatment to the date of curative surgery | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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soft tissue sarcoma, immunotherapy