Promising Objective Response Rate (ORR) Observed in Phase II Trial of Envafolimab for Sarcoma

Promising Objective Response Rate (ORR) Observed in Phase II Trial of Envafolimab for Sarcoma

Source: TRACON Pharmaceuticals

Positive findings from the ongoing Phase II  ENVASARC trial (NCT04480502) demonstrate that envafolimab (KN035), either as a single agent or in combination with ipilimumab (Yervoy), exhibited a double-digit overall response rate (ORR) without significant drug-related toxicities. The study focused on patients with locally advanced, unresectable, or metastatic undifferentiated pleomorphic sarcoma (UPS) or myxofibrosarcoma (MFS) who had previously progressed on one or two lines of chemotherapy.

The interim analysis included data from over 80 patients who were randomly assigned to cohort C (envafolimab alone) or cohort D (envafolimab with ipilimumab). In cohort C, patients who underwent at least 2 computed tomography (CT) scans during the study continued to exhibit a double-digit ORR, while envafolimab demonstrated a well-tolerated safety profile.

Upon completion of a minimum 12-week evaluation for the 46th patient treated with envafolimab, a planned interim analysis will be conducted, which currently indicates exceeding the futility rule 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. We believe the current response rate indicates that we remain on track to achieve the primary endpoint 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.”

James Freddo, M.D., TRACON’s Chief Medical Officer

Envafolimab (KN035) is a subcutaneously injected PD-(L)1 inhibitor, utilizing a single-domain antibody against PD-L1 and marking the first of its kind to receive approval.

The ENVASARC trial, a pivotal multicenter study, commenced dosing in December 2020. The open-label, randomized, non-comparative trial enrolled patients across 30 cancer centers in the United States and the United Kingdom. Participants were assigned to either cohort C, receiving single-agent envafolimab at a dose of 600 mg every 3 weeks via subcutaneous injection, or cohort D, receiving envafolimab at the same dose along with intravenous ipilimumab at 1 mg/kg every 3 weeks for four doses.

To be eligible for participation in the ENVASARC trial, patients aged 12 and above must have confirmed locally advanced or metastatic undifferentiated pleomorphic sarcoma (UPS) or grade ≥ 2 myxofibrosarcoma (MFS) based on histology. They should have experienced disease progression after 1 or 2 prior treatments and have not received an immune checkpoint inhibitor. Additional criteria include an ECOG performance status of 0-1, satisfactory hematologic and organ function, and at least one measurable lesion.

The study’s primary objective is to evaluate the objective response rate (ORR), while secondary endpoints include 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. The sole approved treatment for these patients is Votrient, which achieved a 4% ORR and carries a black box warning for fatal liver toxicity.”

Charles Theuer, MD, PhD, chief executive officer of TRACON

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