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

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Immunotherapy; Sarcoma,Soft Tissue; Radiation Therapy; Neoadjuvant
• Intervention / Treatment: Drug: Pembrolizumab, Eftilagimod alfa

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Estimated): 40
• Phase: Phase 2

Contacts and Locations

Study Locations

• Poland
  • Warsaw, Poland, 00-738
    • Maria Sklodowska-Curie National Research Institute of Oncology

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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;

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: single arm; Systemic therapy with pembrolizumab and eftilagimod alfa is given concurrently with radiotherapy. Surgery is scheduled 5-6 weeks after completion of radiotherapy.	Drug: Pembrolizumab, Eftilagimod alfa; Eftilagimod alfa 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); Other Names: Keytruda; Efti; Eftilagimod alfa

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Maria Sklodowska-Curie National Research Institute of Oncology
• Collaborators: Immutep S.A.S.
• Investigators: Principal Investigator: Katarzyna Kozak, Maria Sklodowska-Curie National Research Institute of Oncology

Study record dates

Study Major Dates

• Study Start (Actual): July 17, 2023
• Primary Completion (Actual): April 30, 2025
• Study Completion (Estimated): April 30, 2027

Study Registration Dates

• First Submitted: October 28, 2023
• First Submitted That Met QC Criteria: November 7, 2023
• First Posted (Actual): November 13, 2023

Study Record Updates

• Last Update Posted (Actual): December 8, 2025
• Last Update Submitted That Met QC Criteria: December 1, 2025
• Last Verified: February 1, 2025

More Information

Terms related to this study

• Keywords: immunotherapy; soft tissue sarcoma
• Additional Relevant MeSH Terms: Neoplasms; Neoplasms by Histologic Type; Neoplasms, Connective and Soft Tissue; Sarcoma; Antineoplastic Agents, Immunological; Immune Checkpoint Inhibitors; Antineoplastic Agents; Molecular Mechanisms of Pharmacological Action; pembrolizumab
• Other Study ID Numbers: EFTISARC-NEO/NIO-0004; 2022-003845-36 (EudraCT Number)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No