On June 20, 2023 TRACON Pharmaceuticals (NASDAQ: TCON), a clinical stage biopharmaceutical company utilizing a cost-efficient, CRO-independent product development platform to advance its pipeline of novel targeted cancer therapeutics and to partner with other life science companies, reported the positive results of a six-month independent data monitoring committee (IDMC) review for the ongoing ENVASARC Phase 2 pivotal trial (Press release, Tracon Pharmaceuticals, JUN 20, 2023, View Source [SID1234632799]).
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The IDMC reviewed interim safety and efficacy data from more than 80 patients equally randomized into cohort C of single agent envafolimab or cohort D of envafolimab given in combination with Yervoy. Patients in cohort C who had at least two on study CT scans continued to demonstrate a double-digit ORR assessed by investigator and blinded independent central review. Envafolimab was well tolerated without a single > grade 2 drug related adverse event. A planned interim analysis in the third quarter will be conducted after the 46th patient treated with envafolimab has completed a minimum of 12 weeks of efficacy evaluations and includes 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, M.D., TRACON’s Chief Medical Officer. "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."
The combination of envafolimab with Yervoy did not demonstrate synergy when compared to single agent envafolimab and the Company will terminate enrollment in cohort D. This is expected to result in a reduction in trial costs and acceleration of the timeline to final ENVASARC data.
Enrollment of the separate trial of TRACON’s CTLA-4 antibody YH001 with envafolimab and doxorubicin will continue, based on multiple responses seen in the Phase 1 portion of the trial to date using a higher dose of the CTLA-4 antibody. Phase 1 is designed to determine the optimal dose of YH001 in combination with envafolimab and doxorubicin, and the Company expects to report trial data at the Connective Tissue Oncology Society (CTOS) annual meeting in November.
"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, M.D., Ph.D., TRACON’s Chief Executive Officer. "The sole approved treatment for these patients is Votrient, which achieved a 4% ORR and carries a black box warning for fatal liver toxicity."
About Envafolimab
Envafolimab (KN035), a single-domain antibody against PD-L1 invented by Alphamab Oncology and licensed by TRACON, is the first approved subcutaneously injected PD-(L)1 inhibitor. Envafolimab was approved by the Chinese NMPA in November 2021 in adult patients with MSI-H/dMMR advanced solid tumors who failed systemic treatment and have no satisfactory alternative treatment options. In December 2019, Alphamab Oncology, 3D Medicines and TRACON entered into a collaboration whereby TRACON has the right to develop and commercialize envafolimab in soft tissue sarcoma in North America. Envafolimab is currently being studied in the ENVASARC Phase 2 pivotal trial in the United States sponsored by TRACON and a Phase 3 pivotal trial in combination with gemcitabine and oxaliplatin in advanced biliary tract cancer patients in China sponsored by TRACON’s corporate partners, Alphamab Oncology and 3D Medicines. TRACON has received orphan drug designation from the U.S. Food and Drug Administration for envafolimab for patients with soft tissue sarcoma and fast track designation from the U.S. Food and Drug Administration for envafolimab (KN035) for patients with locally advanced, unresectable or metastatic undifferentiated pleomorphic sarcoma (UPS) and myxofibrosarcoma (MFS) who have progressed on one or two prior lines of chemotherapy.
About ENVASARC (NCT04480502)
The ENVASARC pivotal trial is a multicenter, open label, randomized, non-comparative, parallel cohort study at 30 top cancer centers in the United States and the United Kingdom that began dosing in December 2020. ENVASARC is enrolling patients with UPS or MFS who have progressed following one or two lines of prior treatment and have not received an immune checkpoint inhibitor. A total of 80 patients will receive treatment with single agent envafolimab at 600 mg every three weeks. The primary endpoint is objective response rate by central review with duration of response a key secondary endpoint.