Immunotherapy, Neoadjuvant, Radiation Therapy, Sarcoma,Soft Tissue
Conditions
Keywords
soft tissue sarcoma, immunotherapy
Brief 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 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.
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.
Interventions
DRUGPembrolizumab, 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)
Sponsors
Immutep S.A.S.
Maria Sklodowska-Curie National Research Institute of Oncology
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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;
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Pathologic response | At the time of definitive surgical treatment | The primary efficacy endpoint is a percent tumor hyalinization as a marker of response to treatment assessed at the time of surgical resection. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of participants completing neoadjuvant therapy | 2 years | Number of patients completing neoadjuvant treatment and having a curative surgery according to the protocol |
| Disease-free survival (DFS) | From the date of curative surgery to the date of first recurrence or death (whatever the cause), whichever occurs first | 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 |
| Local recurrence-free survival (LRFS) | From the date of curative surgery to the date of first local recurrence or date of death (whatever the cause), whichever occurs first | 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. |
| Number of Participants Experiencing Adverse Events (AEs) | 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). | 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. |
| Overall survival (OS) | From the date of curative surgery up to the date of death or the last date the participant was known to be alive | 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. |
| Response rate | From the date of the first dose of treatment to the date of curative surgery | Radiologic Response To Neoadjuvant Treatment using RECIST 1.1 |
| Distant metastasis-free survival (DMFS) | From the date of curative surgery to the date of first distant metastasis or date of death (whatever the cause), whichever occurs first | 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. |
Countries
Poland
Outcome results
None listed