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

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

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Undifferentiated Pleomorphic Sarcoma; Myxofibrosarcoma
• Intervention / Treatment: Biological: Envafolimab; Drug: Ipilimumab

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.

• Study Type: Interventional
• Enrollment (Actual): 207
• Phase: Phase 2

Contacts and Locations

Study Locations

• United Kingdom
  • London, United Kingdom, SW3 6JJ
    • Royal Marsden
• United States
  • Arizona
    • Tucson, Arizona, United States, 85721
      • University of Arizona
  • California
    • Los Angeles, California, United States, 90095
      • University of California, Los Angeles
    • Santa Monica, California, United States, 90403
      • Sarcoma Oncology Research Center
    • Stanford, California, United States, 94305
      • Stanford University
  • Colorado
    • Aurora, Colorado, United States, 80045
      • University of Colorado
  • Florida
    • Jacksonville, Florida, United States, 32224
      • Mayo Clinic, Jacksonville
    • Miami, Florida, United States, 33136
      • University of Miami
    • Tampa, Florida, United States, 33612
      • H. Lee Moffitt Cancer Center
  • Illinois
    • Evanston, Illinois, United States, 60208
      • Northwestern University
  • Maryland
    • Baltimore, Maryland, United States, 21218
      • Johns Hopkins University
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital
    • Boston, Massachusetts, United States, 02215
      • Dana Farber Cancer Institute
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • University of Michigan
  • Minnesota
    • Rochester, Minnesota, United States, 55901
      • Mayo Clinic Rochester
  • Missouri
    • Saint Louis, Missouri, United States, 63130
      • Washington University in St. Louis
  • New York
    • New York, New York, United States, 10065
      • Memorial Sloan Kettering Cancer Center
    • New York, New York, United States, 10027
      • Columbia University
  • North Carolina
    • Durham, North Carolina, United States, 27708
      • Duke University
  • Ohio
    • Cleveland, Ohio, United States, 44106
      • University Hospitals
    • Cleveland, Ohio, United States, 89106
      • Cleveland Clinic
    • Columbus, Ohio, United States, 43210
      • Ohio State University
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19106
      • University of Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19107
      • Thomas Jefferson University (Sidney Kimmel Cancer Center)
    • Pittsburgh, Pennsylvania, United States, 15260
      • University of Pittsburgh
  • Tennessee
    • Nashville, Tennessee, United States, 37235
      • Vanderbilt University
  • Utah
    • Salt Lake City, Utah, United States, 84112
      • Huntsman Cancer Institute
  • Virginia
    • Richmond, Virginia, United States, 23284
      • Virginia Commonwealth University
  • Washington
    • Seattle, Washington, United States, 98109
      • Seattle Cancer Care Alliance
  • Wisconsin
    • Wauwatosa, Wisconsin, United States, 53226
      • Medical College of Wisconsin

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 8 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort A; Patients treated with 300 mg of single agent envafolimab every three weeks	Biological: Envafolimab; PD-L1 single domain antibody for subcutaneous injection.; Other Names: KN035
Experimental: Cohort B; 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; PD-L1 single domain antibody for subcutaneous injection.; Other Names: KN035; Drug: Ipilimumab; CTLA-4 monoclonal antibody; Other Names: Yervoy
Experimental: Cohort C; Patients treated with 600 mg of single agent envafolimab every three weeks	Biological: Envafolimab; PD-L1 single domain antibody for subcutaneous injection.; Other Names: KN035
Experimental: Cohort D; 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; PD-L1 single domain antibody for subcutaneous injection.; Other Names: KN035; Drug: Ipilimumab; CTLA-4 monoclonal antibody; Other Names: Yervoy

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure	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

Collaborators and Investigators

• Sponsor: Tracon Pharmaceuticals Inc.
• Investigators: Study Director: Charles Theuer, MD, PhD, Tracon Pharmaceuticals Inc.

Study record dates

Study Major Dates

• Study Start (Actual): December 9, 2020
• Primary Completion (Estimated): October 1, 2024
• Study Completion (Estimated): October 1, 2024

Study Registration Dates

• First Submitted: July 16, 2020
• First Submitted That Met QC Criteria: July 16, 2020
• First Posted (Actual): July 21, 2020

Study Record Updates

• Last Update Posted (Actual): May 17, 2024
• Last Update Submitted That Met QC Criteria: May 15, 2024
• Last Verified: May 1, 2024

More Information

Terms related to this study

• Keywords: sarcoma
• Additional Relevant MeSH Terms: Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Connective Tissue; Neoplasms, Fibrous Tissue; Histiocytoma; Sarcoma; Histiocytoma, Malignant Fibrous; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Antineoplastic Agents, Immunological; Immune Checkpoint Inhibitors; Ipilimumab
• Other Study ID Numbers: KN035SAR201

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No