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.

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.

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