Myxofibrosarcoma, Undifferentiated Pleomorphic Sarcoma
Conditions
Keywords
sarcoma
Brief summary
This is a multicenter open-label, randomized, non-comparative, parallel cohort pivotal study of treatment with envafolimab (cohort A and C) or envafolimab combined with ipilimumab (cohort B and D) in patients with locally advanced, unresectable or metastatic undifferentiated pleomorphic sarcoma (UPS)/myxofibrosarcoma (MFS) who have progressed on one or two lines of chemotherapy.
Detailed description
This is a multicenter open-label, randomized, non-comparative, parallel cohort pivotal study of treatment with envafolimab (cohort A and C) or envafolimab combined with ipilimumab (cohort B and D) in patients with locally advanced, unresectable or metastatic UPS/MFS who have progressed on one or two lines of chemotherapy. Patients were previously assigned at random into one of two cohorts: cohort A of 80 patients who received single agent envafolimab (300 mg every 3 weeks by subcutaneous (SC) injection) or cohort B of 80 patients who received envafolimab (300 mg every 3 weeks by SC injection) in combination with ipilimumab (1 mg/kg every 3 weeks intravenously for four doses). Following amendment #3, patients will be assigned at random into one of two cohorts: cohort C of 80 patients who will receive single agent envafolimab (600 mg every 3 weeks by subcutaneous (SC) injection) or cohort D of 80 patients who will receive envafolimab 600 mg every 3 weeks by SC injection) in combination with ipilimumab (1 mg/kg every 3 weeks intravenously for four doses). Following amendment #4, enrollment into cohort D was terminated and no further interim analyses will be conducted on this cohort.
Interventions
BIOLOGICALEnvafolimab
PD-L1 single domain antibody for subcutaneous injection.
DRUGIpilimumab
CTLA-4 monoclonal antibody
Sponsors
Tracon Pharmaceuticals Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
12 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Histologically confirmed locally advanced or metastatic undifferentiated pleomorphic sarcoma (UPS) or grade ≥ 2 myxofibrosarcoma (MFS) * Documented progression following systemic chemotherapy * At least one measurable lesion * Eastern Cooperative Oncology Group performance status of 0 or 1 * Adequate hematologic and organ function
Exclusion criteria
* More than two prior lines of chemotherapy for UPS/MFS * Prior immune checkpoint inhibitor or immunomodulatory therapy * Active autoimmune disease that has required systemic treatment * Major surgery within 4 weeks of dosing of investigational agent * Active additional malignancy * Pericardial effusion, pleural effusion, or ascites * Central nervous system metastases and/or carcinomatous meningitis * Active hepatitis or cirrhosis * Interstitial lung disease * Unwilling to apply highly effective contraception during the study * Other concurrent severe and/or uncontrolled medical conditions that would, in the investigator's judgment, contraindicate patient participation in the clinical study
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Objective response rate (ORR) by RECIST 1.1 assessed by blinded independent central review | 40 months |
Secondary
| Measure | Time frame |
|---|---|
| Disease control rate (DCR) assessed by blinded independent central review | 40 months |
| Progression free survival (PFS) assessed by blinded independent central review | 40 months |
| Overall survival (OS) | 40 months |
| Characterize envafolimab pharmacokinetics (PK) in patients receiving envafolimab as a single agent and in combination with ipilimumab | 40 months |
| Duration of response (DR) assessed by blinded independent central review | 40 months |
| Objective response rate (ORR) by investigator assessment | 40 months |
| Progression free survival (PFS) by investigator assessment | 40 months |
| Characterize the immunogenicity of envafolimab and ipilimumab | 40 months |
| Characterize ipilimumab PK in patients given ipilimumab with envafolimab | 40 months |
Countries
United Kingdom, United States
Outcome results
None listed