Clinical trial NCT04480502: ENVASARC: Envafolimab And Envafolimab With Ipilimumab In Patients With Undifferentiated Pleomorphic Sarcoma Or Myxofibrosarcoma
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
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Undifferentiated Pleomorphic Sarcoma
Myxofibrosarcoma
Keywords: sarcoma
Lead sponsor: Tracon Pharmaceuticals Inc.
Sponsor class: INDUSTRY
First posted: 2020-07-21
Enrollment: 207
Sex: ALL
Minimum age (years): 12
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Objective response rate (ORR) by RECIST 1.1 assessed by blinded independent central review
timeFrame: 40 months
Secondary outcomes:
measure: Duration of response (DR) assessed by blinded independent central review
timeFrame: 40 months
measure: Disease control rate (DCR) assessed by blinded independent central review
timeFrame: 40 months
measure: Progression free survival (PFS) assessed by blinded independent central review
timeFrame: 40 months
measure: Overall survival (OS)
timeFrame: 40 months
measure: Characterize envafolimab pharmacokinetics (PK) in patients receiving envafolimab as a single agent and in combination with ipilimumab
timeFrame: 40 months
measure: Characterize ipilimumab PK in patients given ipilimumab with envafolimab
timeFrame: 40 months
measure: Objective response rate (ORR) by investigator assessment
timeFrame: 40 months
measure: Progression free survival (PFS) by investigator assessment
timeFrame: 40 months
measure: Characterize the immunogenicity of envafolimab and ipilimumab
timeFrame: 40 months
Other outcomes:
Locations:
city: Tucson
country: United States
facility: University of Arizona
state: Arizona
city: Los Angeles
country: United States
facility: University of California, Los Angeles
state: California
city: Santa Monica
country: United States
facility: Sarcoma Oncology Research Center
state: California
city: Stanford
country: United States
facility: Stanford University
state: California
city: Aurora
country: United States
facility: University of Colorado
state: Colorado
city: Jacksonville
country: United States
facility: Mayo Clinic, Jacksonville
state: Florida
city: Miami
country: United States
facility: University of Miami
state: Florida
city: Tampa
country: United States
facility: H. Lee Moffitt Cancer Center
state: Florida
city: Evanston
country: United States
facility: Northwestern University
state: Illinois
city: Baltimore
country: United States
facility: Johns Hopkins University
state: Maryland
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Boston
country: United States
facility: Dana Farber Cancer Institute
state: Massachusetts
city: Ann Arbor
country: United States
facility: University of Michigan
state: Michigan
city: Rochester
country: United States
facility: Mayo Clinic Rochester
state: Minnesota
city: Saint Louis
country: United States
facility: Washington University in St. Louis
state: Missouri
city: New York
country: United States
facility: Columbia University
state: New York
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
city: Durham
country: United States
facility: Duke University
state: North Carolina
city: Cleveland
country: United States
facility: University Hospitals
state: Ohio
city: Cleveland
country: United States
facility: Cleveland Clinic
state: Ohio
city: Columbus
country: United States
facility: Ohio State University
state: Ohio
city: Philadelphia
country: United States
facility: University of Pennsylvania
state: Pennsylvania
city: Philadelphia
country: United States
facility: Thomas Jefferson University (Sidney Kimmel Cancer Center)
state: Pennsylvania
city: Pittsburgh
country: United States
facility: University of Pittsburgh
state: Pennsylvania
city: Nashville
country: United States
facility: Vanderbilt University
state: Tennessee
city: Salt Lake City
country: United States
facility: Huntsman Cancer Institute
state: Utah
city: Richmond
country: United States
facility: Virginia Commonwealth University
state: Virginia
city: Seattle
country: United States
facility: Seattle Cancer Care Alliance
state: Washington
city: Wauwatosa
country: United States
facility: Medical College of Wisconsin
state: Wisconsin
city: London
country: United Kingdom
facility: Royal Marsden
Study officials:
affiliation: Tracon Pharmaceuticals Inc.
name: Charles Theuer, MD, PhD
role: STUDY_DIRECTOR
References: