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

The phase 2 ENVASARC trial (NCT04480502), which is examining the PD-L1 antibody envafolimab (KN035) with and without ipilimumab (Yervoy) in patients with undifferentiated pleomorphic sarcoma and myxofibrosarcoma, has been recommended by the Independent Data Monitoring Committee to continue as planned.¹

The recommendation follows the review of safety data on over 20 patients who have been enrolled to the trial, to date. The data included information from over 10 patients who were enrolled to cohort A and received treatment with envafolimab monotherapy, and over 10 patients who were enrolled to cohort B and received envafolimab plus ipilimumab.

“We are pleased with the recommendation of the Data Monitoring Committee to continue the ENVASARC pivotal trial as planned,” James Freddo, MD, chief medical officer of TRACON Pharmaceuticals, stated in a press release. “Envafolimab has been well tolerated as a single agent and when combined with [ipilimumab] in these patients with refractory sarcoma who are enrolled in the ENVASARC trial. Based on the current accrual rate, we expect the Data Monitoring Committee to review additional safety data in the third quarter and to review interim efficacy data in the fourth quarter of this year.”

Envafolimab is the first subcutaneously injected PD-(L)1 inhibitor to be investigated in pivotal trials, according to TRACON Pharmaceuticals, the drug developer.

The multicenter, open-label, non-comparative, parallel-cohort ENVASARC study is being done at about 25 top cancer centers throughout the United States, and dosing was initiated in December 2020.

The trial is anticipated to enroll a total of 160 patients with undifferentiated pleomorphic sarcoma and myxofibrosarcoma who have progressed after 1 or 2 prior lines of treatment and have not received an immune checkpoint inhibitor.

To be eligible for enrollment, patients needed to have histologically confirmed locally advanced or metastatic undifferentiated pleomorphic sarcoma or grade 2 or higher myxofibrosarcoma.² They also needed to have documented progression after systemic chemotherapy, at least 1 measurable lesion, an ECOG performance status of 0 or 1, and acceptable hematologic and organ function.

If patients had previously received more than 2 lines of chemotherapy for their disease, previous checkpoint inhibitors or immunomodulatory therapy, or active autoimmune disease that required systemic therapy, they were excluded. Other exclusion criteria included major surgery within 4 weeks of dosing, active additional malignancy, active hepatitis or cirrhosis, and interstitial lung disease, among others.

Eighty patients will be enrolled to cohort A, which is examining envafolimab monotherapy at a dose of 300 mg every 3 weeks, and 80 patients will be enrolled to cohort B, which is evaluating envafolimab at 300 mg every 3 weeks in combination with ipilimumab at 1 mg/kg 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, while secondary end points include duration of response, disease control rate, progression-free survival, overall survival, and pharmacokinetics.

Envafolimab has also been evaluated as a monotherapy in Chinese patients with microsatellite instability–high (MSI-H)/deficient mismatch repair (dMMR) advanced solid tumors. The agent is also under investigation in an ongoing phase 3 trial that is evaluating its use in combination with gemcitabine and oxaliplatin in Chinese patients with biliary tract cancers.

A new drug application for envafolimab as a treatment for patients with MSI-H/dMMR cancer has been submitted to China’s National Medical Products Administration. The application was accepted for review in December 2020 and subsequently granted priority review in January 2021.

References

1. 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 June 2, 2021. https://bit.ly/3uLHM7U
2. ENVASARC: envafolimab and envafolimab with ipilimumab in patients with undifferentiated pleomorphic sarcoma or myxofibrosarcoma (ENVASARC). ClinicalTrials.gov. Updated May 6, 2021. Accessed June 2, 2021. https://clinicaltrials.gov/ct2/show/NCT04480502