Phase 2 Study of Envafolimab Displays Encouraging ORR in Sarcoma


Among patients with unresectable or metastatic undifferentiated pleomorphic sarcoma or myxofibrosarcoma, envafolimab generated positive efficacy data with a well-tolerated safety profile.

Single-agent envafolimab (KN035) demonstrated a double-digit overall response rate (ORR) without any greater than grade 2 drug related toxicities among patients with locally advanced, unresectable or metastatic undifferentiated pleomorphic sarcoma (UPS) or myxofibrosarcoma (MFS) who have progressed on one or two lines of chemotherapy, according to positive results from the ongoing phase 2 ENVASARC trial (NCT04480502).1

Interim safety and efficacy data come from over 80 patients who were randomized into cohort C of the phase 2 study and given envafolimab, or cohort D and given envafolimab with ipilimumab (Yervoy). In cohort C, patients who had at least 2 on study CT scans continued to demonstrate a double-digit ORR, and the safety profile of envafolimab was well tolerated.

Once the 46th patient treated with envafolimab has completed a minimum of 12 weeks of efficacy evaluations, a planned interim analysis will be conducted, including a futility rule that is currently being exceeded based on available data.

“We are pleased with the single agent activity of envafolimab that continues to generate a double-digit ORR, as well as the safety data showing envafolimab is well tolerated,” said James Freddo, MD, chief medical officer of TRACON, in a press release. “We believe the current response rate indicates that we remain on track to achieve the primary end point of the study of a minimum 11.25% objective response rate. We remain excited by the emerging data and for envafolimab’s potential to become a differentiated treatment for sarcoma patients.”

Envafolimab (KN035) is a single-domain antibody against PD-L1 and the first subcutaneously injected PD-(L)1 inhibitor to be approved.

The pivotal, multicenter, open-label, randomized, non-comparative, parallel cohort ENVASARC trial enrolled patients at 30 cancer centers in the United States and the United Kingdom and began dosing in December 2020. Patients were randomly assigned into cohort C of and given single agent envafolimab at 600 mg every 3 weeks by subcutaneous (SC) injection, or cohort D and given envafolimab 600 mg every 3 weeks by SC injection in combination with ipilimumab at 1 mg/kg every 3 weeks intravenously for 4 doses.2

Patients aged 12 years and older were eligible for enrollment in ENVASARC if they have histologically confirmed locally advanced or metastatic UPS or grade ≥ 2 MFS, have progressed following 1 or 2 lines of prior treatment, and have not received an immune checkpoint inhibitor. Other requirements include an ECOG performance status of 0-1, adequate hematologic and organ function, and at least 1 measurable lesion.

The primary end point of the study is ORR with secondary end points of duration of response, disease control rate, progression-free survival, overall survival, and pharmacokinetics.

“Achieving a double-digit ORR with a well-tolerated safety profile positions envafolimab to become a potentially compelling treatment option for patients with the refractory sarcoma subtypes of UPS and MFS,” said Charles Theuer, MD, PhD, chief executive officer of TRACON, in the press release. “The sole approved treatment for these patients is Votrient, which achieved a 4% ORR and carries a black box warning for fatal liver toxicity.”

TRACON Pharmaceuticals announces positive results based on ongoing double-digit objective response rate for single agent envafolimab in the ENVASARC phase 2 pivotal trial. News release. TRACON Pharmaceuticals, Inc. June 20, 2023. Accessed June 21, 2023.
ENVASARC: envafolimab and envafolimab with ipilimumab in patients with undifferentiated pleomorphic sarcoma or myxofibrosarcoma (ENVASARC). Updated April 12, 2023. Accessed June 21, 2023.
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