Twelve-week safety data from the phase 2 ENVASARC trial of envafolimab alone and in combination with ipilimumab in patients with undifferentiated pleomorphic sarcoma and myxofibrosarcoma support proceeding with enrollment of patients in the trial.
Trial Name: ENVASARC: Envafolimab And Envafolimab With Ipilimumab In Patients With Undifferentiated Pleomorphic Sarcoma Or Myxofibrosarcoma (ENVASARC)
ClinicalTrials.gov Identifier: NCT04480502
Sponsor: Tracon Pharmaceuticals Inc.
Recruitment Contact: Charles Theuer, MD, PhD, 858-550-0780, clinicaltrials@traconpharma.com
Completion Date: June 2024
The Independent Data Monitoring Committee for the phase 2 ENVASARC trial (NCT04480502) of envafolimab (KN035) in patients with locally advanced, unresectable or metastatic undifferentiated pleomorphic sarcoma (UPS) and myxofibrosarcoma (MFS) who have progressed on 1 or 2 prior lines of chemotherapy has recommended the trial proceed as planned, according to TRACON Pharmaceuticals, Inc.1
Envafolimab is a single-domain antibody which works against PD-L1. The agent is the first approved subcutaneously injected PD-L1 inhibitor.
The approval to process as planned comes after a positive review of 12-week safety data which evaluated more than 10 patients enrolled into cohort C of the the trial and over 10 in cohort D.
Patients in cohort C received single-agent envafolimab at 600 mg administered subcutaneously every 3 weeks while those enrolled in cohort D were administered treatment with envafolimab at 600 mg subcutaneously every 3 weeks in combination with intravenous ipilimumab (Yervoy).
“Envafolimab at the 600 mg dose has been well tolerated as a single agent and when combined with [Ipilimumab] in refractory sarcoma patients who are enrolled in the ENVASARC trial. Accrual continues to exceed projections and we remain on track for the Independent Data Monitoring Committee to review interim efficacy data in the fourth quarter of this year,” said James Freddo, MD, chief medical officer of TRACON Pharmaceuticals, Inc, in the press release.
The pivotal, multicenter, open-label, randomized, non-comparative, ENVASARC trial is expected to enroll more than 160 patients with locally advanced, unresectable or metastatic UPS and MFS who have progressed on 1-2 prior lines of chemotherapy and who have not received an immune checkpoint inhibitor.2
Patients aged 12 years and older with histologically confirmed locally advanced or metastatic UPS or grade 2 or higher MFS are eligible for enrollment in the study if they also have documented progression following systemic chemotherapy, at least 1 measurable lesion, an ECOG performance status of 0 or 1, and adequate hematologic and organ function. Patients must also be willing to use highly effective contraception during the duration of the study.
Those who have received over 2 prior lines of chemotherapy for UPS or MFS, a prior immune checkpoint inhibitor, prior immunomodulatory therapy, have active autoimmune disease that has required systemic treatment, have had a major surgery within 4 weeks of dosing of investigational agent, or who have an active additional malignancy will be excluded from the trial. Further exclusion criteria include pericardial effusion, pleural effusion, or ascites, central nervous system metastases, carcinomatous meningitis, active hepatitis or cirrhosis, and interstitial lung disease.
Among those included, 80 patients will be enrolled into a cohort of treatment consisting of single agent envafolimab at 600 mg every 3 weeks while the other 80 patients will be enrolled into a cohort of treatment with envafolimab at 600 mg every 3 weeks in combination with ipilimumab.
The primary end point of the study is objective response rate by central review with the key secondary end point of duration of response.
Other secondary end points include disease control rate, progression-free survival, overall survival, to characterize the pharmacokinetics of envafolimab and ipilimumab in patients receiving envafolimab as a single agent and in combination with ipilimumab, and to characterize the immunogenicity of envafolimab and ipilimumab.
