Envafolimab Produces Ongoing Responses, Tolerability in Sarcoma Subtypes


The agent continues to produce ongoing responses in a cohort of patients with undifferentiated pleomorphic sarcoma or myxofibrosarcoma in the phase 2 ENVASARC trial.

The FDA previously granted fast track designation to envafolimab for patients with locally advanced, unresectable or metastatic UPS and MFS previously treated with chemotherapy in September 2022.

The FDA previously granted fast track designation to envafolimab for patients with locally advanced, unresectable or metastatic UPS and MFS previously treated with chemotherapy in September 2022.

Treatment with envafolimab (KN035) alone yielded an overall response rate (ORR) exceeding the futility rule of the phase 2 ENVASARC trial (NCT04480502) among patients with undifferentiated pleomorphic sarcoma (UPS) or myxofibrosarcoma (MFS), according to a press release from TRACON Pharmaceuticals.1

The trial update follows a 6-month review by an independent data monitoring committee of outcomes in cohort C, in which the agent was administered as a monotherapy, and cohort D, in which it was administered in combination with ipilimumab (Yervoy).

Patients in cohort C who had undergone 2 or more CT scans during the study maintained a double-digit ORR as assessed by both investigators and blinded independent central review (BICR). Moreover, envafolimab did not produce any treatment-related adverse effects more severe than grade 2.

An interim analysis will occur later this year after at least 12 weeks of efficacy evaluations have been completed for the forty-sixth patient treated with envafolimab. This analysis will include a futility rule that has already been surpassed by the current data.

“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,” Charles Theuer, MD, PhD, chief executive officer at TRACON, said in the press release.

Envafolimab is a single-domain, subcutaneously injected PD-L1 inhibitor. In the multicenter, open-label, parallel cohort ENVASARC study, 80 patients from 30 cancer centers were randomly assigned into cohort C or D. Patients in both cohorts received envafolimab at a dose of 600 mg every 3 weeks, and patients in cohort D additionally received ipilimumab at a dose of 1 mg/kg every 3 weeks for a total of 4 doses.

The trial’s primary end point is ORR by BICR. Secondary end points include duration of response, disease control rate, progression-free survival (PFS) by BICR, and overall survival. Investigator-assessed ORR and PFS are also secondary end points.

According to the press release, the combination of envafolimab and ipilimumab evaluated in cohort D was not synergistic or effective compared with the single-agent treatment. As such, enrollment in this cohort will be terminated.

To be included in the ENVASARC trial, patients with UPS or MFS needed to have disease progression following no more than 2 prior lines of treatment and could not have received any prior immune checkpoint inhibitor therapy. Adequate hematologic and organ function and an ECOG performance status of 0 or 1 were among the other inclusion criteria.

Patients with active autoimmune disease requiring systemic therapy were excluded from the trial. Other exclusion criteria included any active additional malignancy, pericardial or pleural effusion, or ascites. The presence of central nervous system metastasis was also grounds for exclusion.

“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 end point of the study…. We remain excited by the emerging data and for envafolimab’s potential to become a differentiated treatment for sarcoma patients,” James Freddo, MD, chief medical officer at TRACON, concluded.

The FDA previously granted fast track designation to envafolimab for patients with locally advanced, unresectable or metastatic UPS and MFS previously treated with chemotherapy in September 2022.2 Supporting data for this designation came from the ENVASARC trial.


  1. 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. June 20, 2023. Accessed June 21, 2023. https://bit.ly/3Ni0hfj
  2. TRACON Pharmaceuticals announces fast track designation by the FDA for envafolimab for the treatment of the soft tissue sarcoma subtypes of UPS and MFS. News Release. TRACON Pharmaceuticals. September 14, 2022. Accessed June 26, 2023. https://bit.ly/3CigAmO
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