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

Immunotherapy Clinical Trial

— EFTISARC-NEO  

Official title:

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)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06128863
• Other study ID #: EFTISARC-NEO/NIO-0004
• Secondary ID: 2022-003845-36
• Status: Recruiting
• Phase: Phase 2
• Start date: July 17, 2023
• Est. completion date: April 30, 2027

Study information

• Verified date: October 2023
• Source: Maria Sklodowska-Curie National Research Institute of Oncology
• Contact: Katarzyna Kozak
• Phone: +48225462051
• Email: katarzyna.kozak[@]nio.gov.pl
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Description:

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 40
• Est. completion date: April 30, 2027
• Est. primary completion date: April 30, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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:

1. undifferentiated pleomorphic sarcoma (UPS),

2. myxofibrosarcoma,

3. dedifferentiated liposarcoma (DDLPS),

4. myxoid and round cell liposarcoma (MRCLPS),

5. epithelioid sarcoma (ES),

6. angiosarcoma (AS)

7. 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;

Related Conditions & MeSH terms

• Immunotherapy
• Radiation Therapy
• Sarcoma
• Sarcoma,Soft Tissue

Intervention

Drug:
• Pembrolizumab, Eftilagimod alpha
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)

Locations

Country	Name	City	State
Poland	Maria Sklodowska-Curie National Research Institute of Oncology	Warsaw

Sponsors (2)

Lead Sponsor	Collaborator
Maria Sklodowska-Curie National Research Institute of Oncology	Immutep S.A.S.

Country where clinical trial is conducted

Poland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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).
Secondary	Number of participants completing neoadjuvant therapy	Number of patients completing neoadjuvant treatment and having a curative surgery according to the protocol	2 years
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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