ENVASARC: Envafolimab And Envafolimab With Ipilimumab In Patients With Undifferentiated Pleomorphic Sarcoma Or Myxofibrosarcoma

Study Overview
=================
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).

Official Title
-----------------
ENVASARC: A Pivotal Trial Of Envafolimab, And Envafolimab In Combination With Ipilimumab, In Patients With Advanced Or Metastatic Undifferentiated Pleomorphic Sarcoma Or Myxofibrosarcoma Who Have Progressed On Prior Chemotherapy

Conditions
-----------------
Undifferentiated Pleomorphic Sarcoma, Myxofibrosarcoma

Intervention / Treatment
-----------------
* Biological: Envafolimab
* Drug: Ipilimumab


Participation Criteria
=================
Eligibility Criteria
-----------------
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

Ages Eligible for Study
-----------------
Minimum Age: 12 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort A<br>Patients treated with 300 mg of single agent envafolimab every three weeks | Biological: Envafolimab<br>* PD-L1 single domain antibody for subcutaneous injection.<br>* Other names: KN035;|
| Experimental: Cohort B<br>Patients treated with envafolimab in combination with ipilimumab. Envafolimab will be given at 300 mg every three weeks. Ipilimumab will be given at 1 mg/kg every three weeks for a total of four doses. | Biological: Envafolimab<br>* PD-L1 single domain antibody for subcutaneous injection.<br>* Other names: KN035;Drug: Ipilimumab<br>* CTLA-4 monoclonal antibody<br>* Other names: Yervoy;|
| Experimental: Cohort C<br>Patients treated with 600 mg of single agent envafolimab every three weeks | Biological: Envafolimab<br>* PD-L1 single domain antibody for subcutaneous injection.<br>* Other names: KN035;|
| Experimental: Cohort D<br>Patients treated with envafolimab in combination with ipilimumab. Envafolimab will be given at 600 mg every three weeks. Ipilimumab will be given at 1 mg/kg every three weeks for a total of four doses. | Biological: Envafolimab<br>* PD-L1 single domain antibody for subcutaneous injection.<br>* Other names: KN035;Drug: Ipilimumab<br>* CTLA-4 monoclonal antibody<br>* Other names: Yervoy;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective response rate (ORR) by RECIST 1.1 assessed by blinded independent central review |  | 40 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Duration of response (DR) assessed by blinded independent central review |  | 40 months | 
| 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 | 
| Characterize ipilimumab PK in patients given ipilimumab with envafolimab |  | 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 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
sarcoma