Investigators Discontinue Development of Envafolimab for Sarcoma

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The announcement follows results from the ENVASARC trial, where the primary endpoint needed to support a biologics license application was not met.

Investigators of the multicenter, open-label, randomized, parallel cohort ENVASARC study (NCT04480502) sought to evaluate the efficacy of envafolimab in 2 cohorts including patients with locally advanced, unresectable or metastatic undifferentiated pleomorphic sarcoma or myxofibrosarcoma.

Investigators of the multicenter, open-label, randomized, parallel cohort ENVASARC study (NCT04480502) sought to evaluate the efficacy of envafolimab in 2 cohorts including patients with locally advanced, unresectable or metastatic undifferentiated pleomorphic sarcoma or myxofibrosarcoma.

TRACON Pharmaceuticals announced it is terminating development of envafolimab in patients with advanced or metastatic undifferentiated pleomorphic sarcoma (UPS) or myxofibrosarcoma (MFS) after the primary endpoint of objective response rate (ORR) was not met in the phase 2 ENVASARC trial (NCT04480502),according to a press release from the developer.1

A blinded independent central review (BICR) found that the ORR was 5% (n = 4/82), which did not reach the trial’s primary end point of 11%. By not meeting the primary end point, developers were unable to support a biologics license application (BLA) for envafolimab.

Investigators, in terminating development of envafolimab, are exploring strategic short-term alternatives. They plan to leverage their Product Development Platform (PDP) used to conduct 12 phase 1 to 3 oncology trials at more than 120 United States– and Europe-based sites across 10 tumor types over 12 years. Additionally, developers do not expect to disclose related developments until an evaluation of strategic alternatives has been completed or its board of directors conclude disclosure is appropriate or required by law.

“We are proud of our execution of the largest trial ever done in the sarcoma subtypes of undifferentiated pleomorphic sarcoma and myxofibrosarcoma using TRACON’s [PDP],” said Charles Theuer, MD, PhD, chief executive officer at TRACON.1 “While individual patients derived benefit from envafolimab, the response rate by [BICR] in the ENVASARC trial of envafolimab as a single agent does not support a BLA. We are therefore discontinuing all of our clinical development activities and intend to take action to immediately reduce cash burn to better position the company for this strategic alternative process. We plan to leverage the value of our PDP in pursuing strategic alternatives.”

Metastatic UPS and MFS are soft tissue sarcoma subtypes with potential response rates of up to 20% with frontline chemotherapy.2 According to the investigators of the ENVASARC trial, however, efficacy in the second-line setting and beyond is limited. Envafolimab, a subcutaneous injection approved for the treatment of microsatellite instability-high (MSI-H) cancer in China, has shown activity that appeared similar to other PD-1 antibodies administered intravenously in other diseases such as colorectal cancer.

Investigators of the multicenter, open-label, randomized, parallel cohort ENVASARC study sought to evaluate the efficacy of envafolimab in 2 cohorts including patients with locally advanced, unresectable or metastatic UPS or MFS. Patients were assigned to receive 600 mg of envafolimab every 3 weeks by subcutaneous injection (n = 80) or the same dosage of envafolimab combined with 1 mg/kg of ipilimumab (Yervoy) every 3 weeks administered intravenously for 4 doses (n = 80).

The primary end point of each cohort was demonstration of ORR with a 95% CI excluding 5% in each cohort. Secondary end points included duration of response, progression-free survival, and overall survival.

Inclusion criteria included patients 12 years or older with histologically confirmed locally advanced or metastatic UPS or grade 2 or greater MFS. Additional requirements for enrollment included having documented progression following chemotherapy, at least 1 measurable lesion, an ECOG performance status of 0 or 1, and adequate hematologic and organ function.3

Exclusion criteria included more than 2 prior lines of chemotherapy for UPS or MFS, prior treatment with immune checkpoint inhibitor or immunomodulatory therapy, active autoimmune disease requiring systemic treatment, major surgery within 4 weeks of beginning study treatment, and active additional malignancies. Having central nervous system metastases and/or carcinomatous meningitis was also grounds for exclusion from the trial.

References

  1. TRACON Pharmaceuticals announces termination of ENVASARC trial and will explore strategic alternatives leveraging its in-house product development platform. Press release. TRACON Pharmaceuticals, Inc. July 1, 2024. Accessed July 2, 2024. https://tinyurl.com/3krk8s7n
  2. Riedel RF, Chawla SP, Druta M, et al. ENVASARC: A pivotal trial of envafolimab and envafolimab in combination with ipilimumab in patients with advanced or metastatic undifferentiated pleomorphic sarcoma or myxofibrosarcoma who have progressed on prior chemotherapy. J Clin Oncol. 2023;41(suppl 16):TPS11583. doi: 10.1200/JCO.2023.41.16_suppl.TPS11583
  3. ENVASARC: envafolimab And envafolimab With ipilimumab in patients with undifferentiated pleomorphic sarcoma or myxofibrosarcoma (ENVASARC). ClinicalTrials.gov. Accessed July 2, 2024. https://tinyurl.com/3b6m6bmr
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