FDA Streamlines Regulatory Process for Envafolimab in Undifferentiated Pleomorphic Sarcoma and Myxofibrosarcoma

The FDA has granted a fast track designation to envafolimab for the treatment of patients with locally advanced, unresectable, or metastatic undifferentiated pleomorphic sarcoma (UPS) and myxofibrosarcoma (MFS) who have progressed on 1 or 2 prior lines of chemotherapy.¹

The agent is currently under study as a single agent and in combination with ipilimumab (Yervoy) in this population in the pivotal phase 2 ENVASARC trial (NCT04480502).

“We applied for fast track designation based on activity observed in the ENVASARC phase 2 pivotal trial and are pleased to receive this notification from the FDA,” Charles Theuer, MD, PhD, president and chief executive officer of TRACON, said in a press release. “Soft tissue sarcoma is a disease in need of new treatments, and we expect to provide data through the ENVASARC pivotal trial showing superior efficacy and safety of envafolimab compared to currently approved therapy for refractory soft tissue sarcoma.”

The FDA designed the fast track process to facilitate the development and expedite the review of drugs to treat serious or life-threatening diseases or conditions and fill unmet medical needs. Fast track designation can confer important benefits, including the potential eligibility for priority review of a Biologics License Application, if relevant criteria are met.

Envafolimab, a single-domain anti–PD-L1 antibody, is the first approved subcutaneously injected PD-L1 inhibitor. Envafolimab was approved by the Chinese National Medical Products Administration in November 2021 in adult patients with microsatellite instability–high/mismatch repair–deficient advanced solid tumors who failed systemic treatment and have no satisfactory alternative treatment options.

ENVASARC is a multicenter, open-label, randomized, non-comparative, parallel cohort study that is being conducted across 30 cancer centers in the United States and the United Kingdom.^1,2

The expected study enrollment is 230 patients at least 12 years of age with UPS or MFS who have progressed following one or two lines of prior treatment and have not received an immune checkpoint inhibitor.

Additional eligibility criteria state that patients must have at least 1 measurable lesion, an ECOG performance status of 0 or 1, and adequate hematologic and organ function.

The study is divided into 4 cohorts of 80 patients each: A, B, C, and D. In cohort A, patients will receive 300 mg of subcutaneous envafolimab every 3 weeks and in cohort B, patients will receive 300 mg of subcutaneous envafolimab every 3 weeks plus 1 mg/kg of intravenous (IV) ipilimumab every 3 weeks for four doses. In cohorts C and D, patients will receive 600 mg of subcutaneous envafolimab every 3 weeks, and 600 mg of subcutaneous envafolimab every 3 weeks plus 1 mg/kg of IV ipilimumab every 3 weeks for four doses, respectively. Dosing began in December 2020.

The primary end point of the study is objective response rate by central review. Duration of response is a key secondary end point.

“Accrual in the pivotal ENVASARC trial remains robust and we expect to report an independent data monitoring committee interim safety review [and interim efficacy review in the fourth quarter,” Theuer concluded.

In addition to ENVASARC, envafolimab is also under study in a pivotal phase 3 trial (NCT03478488) in combination with gemcitabine and oxaliplatin in patients with advanced biliary tract cancer in China.

References

1. 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 September 15, 2022. https://bit.ly/3BG40Pk
2. ENVASARC: envafolimab and envafolimab with ipilimumab in patients with undifferentiated pleomorphic sarcoma or myxofibrosarcoma (ENVASARC). ClinicalTrials.gov. Updated April 8, 2022. Accessed September 15, 2022. https://clinicaltrials.gov/ct2/show/NCT04480502