Phase 2 ENVASARC Trial of Envafolimab With and Without Ipilimumab in Sarcoma to Continue

James Freddo, MD

An independent data monitoring committee has recommended that the phase 2 ENVASARC trial (NCT04480502) examining envafolimab (KN035) with and without ipilimumab (Yervoy) in patients with undifferentiated pleomorphic sarcoma and myxofibrosarcoma continue as planned.¹

The recommendation follows the review of 12-week safety data from patients enrolled on the trial as of June 30, 2022. The updated safety findings included more than 10 patients enrolled into cohort C for treatment with envafolimab monotherapy administered subcutaneously at 600 mg every 3 weeks, along with more than 10 patients enrolled into cohort D for treatment with the combination of subcutaneous envafolimab at 600 mg given every 3 weeks, plus intravenous (IV) ipilimumab.

“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 [2022],” James Freddo, MD, chief medical officer of TRACON Pharmaceuticals, stated in a press release.

The multicenter, open-label, non-comparative, parallel-cohort ENVASARC study is being conducted at 30 top cancer centers in the United States and United Kingdom, and dosing initiated in December 2020. TRACON expects more than 160 patients with undifferentiated pleomorphic sarcoma and myxofibrosarcoma to enroll in the study.

ENVASARC is enrolling patients with histologically confirmed locally advanced or metastatic undifferentiated pleomorphic sarcoma or grade II or higher myxofibrosarcoma who have documented progression following 1 or 2 lines of systemic chemotherapy.² Patients are also required to have at least 1 measurable lesion, an ECOG performance status of 0 or 1, and adequate hematologic and organ function.

Key exclusion criteria include more than 2 prior lines of chemotherapy, prior treatment with an immune checkpoint inhibitor or immunomodulatory therapy, active autoimmune disease that required systemic treatment, major surgery within 4 weeks of dosing, central nervous metastases, or carcinomatous meningitis.

Patients in cohorts A and B will receive 300 mg of subcutaneous envafolimab every 3 weeks, and patients in cohort B will also be administered 1 mg/kg of IV ipilimumab every 3 weeks for a total of 4 doses. Those enrolled in cohorts C and D will be given 600 mg of subcutaneous envafolimab every 3 weeks, and patients in cohort D will also get 1 mg/kg of IV ipilimumab every 3 weeks for a total of 4 doses.

The primary end point of the trial is objective response rate per blinded independent central review following RECIST v1.1 criteria. Key secondary end points consist of duration of response, disease control rate, progression-free survival, overall survival, and pharmacokinetics.

Previously in June 2021, an independent data monitoring committee gave the green light for the ENVASARC trial to continue as planned after reviewing safety data from more than 20 patients enrolled in cohorts A and B.³

References

1. TRACON Pharmaceuticals announces results of independent data monitoring committee review of 12 week safety data from ENVASARC phase 2 pivotal trial - trial to proceed as planned. News release. TRACON Pharmaceuticals, Inc. October 6, 2022. Accessed October 7, 2022. https://yhoo.it/3rzPlPX
2. ENVASARC: envafolimab and envafolimab with ipilimumab in patients with undifferentiated pleomorphic sarcoma or myxofibrosarcoma (ENVASARC). ClinicalTrials.gov. Updated April 8, 2022. Accessed October 7, 2022. https://clinicaltrials.gov/ct2/show/NCT04480502
3. TRACON Pharmaceuticals announces results of independent data monitoring committee review of safety data from ENVASARC pivotal trial. News release. TRACON Pharmaceuticals, Inc. June 1, 2021. Accessed October 7, 2022. https://bit.ly/3uLHM7U