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

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.

• Envafolimab (Biological), also known as KN035: PD-L1 single domain antibody for subcutaneous injection.
• Ipilimumab (Drug), also known as Yervoy: CTLA-4 monoclonal antibody

Primary outcomes

• Objective response rate (ORR) by RECIST 1.1 assessed by blinded independent central review [40 months]

Secondary outcomes

• 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]

Sex: All, ages: 12 Years to any

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

• Charles Theuer, MD, PhD, Study director, Tracon Pharmaceuticals Inc.