On December 27, 2021 TRACON Pharmaceuticals (NASDAQ: TCON), a clinical stage biopharmaceutical company focused on the development and commercialization of novel targeted cancer therapeutics reported the Independent Data Monitoring Committee (IDMC) for the ongoing ENVASARC pivotal trial recommended continued accrual as planned in both cohort A of single agent envafolimab and cohort B of envafolimab given with Yervoy (ipilimumab) (Press release, Tracon Pharmaceuticals, DEC 27, 2021, View Source [SID1234597767]).

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The IDMC reviewed interim safety and efficacy data from 18 patients enrolled into each cohort who completed a minimum of 12 weeks of efficacy evaluations (two on-treatment scans). The ORR by BICR in each cohort satisfied the prespecified futility rule. Envafolimab was well tolerated, with only a single Grade 3 related adverse event reported in 36 patients.

Based on the highly tolerable safety profile and the significantly higher ORR observed in lower weight patients, the IDMC recommended increasing the envafolimab dose to 600 mg Q3W, which is twice the current envafolimab dose of 300 mg Q3W. Given the robust activity demonstrated by higher doses of envafolimab in completed studies, including in the pivotal trial in MSI-H/dMMR cancer that was the basis for approval in China, TRACON agrees with the IDMC guidance and will recommend this dose to the U.S. Food and Drug Administration (FDA) through a protocol amendment.

"We are pleased that envafolimab has demonstrated clear activity as a single agent and in combination with Yervoy even at this early 12-week time point. The increase in dose is supported by the safety profile observed to date, which we believe may further differentiate envafolimab from the current standard of care. Envafolimab has been dosed safely at doses that are eight-fold higher than those currently used in ENVASARC. We therefore believe a doubling of the dose can be administered safely and result in higher envafolimab exposures, thereby potentially optimizing envafolimab’s efficacy for the greatest number of sarcoma patients," said James Freddo, M.D., TRACON’s Chief Medical Officer. "This interim analysis is an important milestone for Tracon. We look forward to working closely with the FDA on an amendment to implement the IDMC’s recommendations. We are excited by the emerging data and for envafolimab’s potential to become a differentiated treatment for sarcoma patients."

About Envafolimab

Envafolimab (KN035), a single-domain antibody against PD-L1 invented by Alphamab Oncology, is the first subcutaneously injected PD-(L)1 inhibitor approved by the 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 pivotal ENVASARC Phase 2 trial in the U.S. 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.

About ENVASARC (NCT04480502)

The ENVASARC pivotal trial is a multicenter, open label, randomized, non-comparative, parallel cohort study at approximately 25 top cancer centers in the United States that began dosing in December 2020. TRACON expects the trial to enroll 160 patients with UPS or MFS who have progressed following one or two lines of prior treatment and have not received an immune checkpoint inhibitor, with 80 patients enrolled into cohort A of treatment with single agent envafolimab and 80 patients enrolled into cohort B of treatment with envafolimab and Yervoy. The primary endpoint is ORR by BICR with duration of response a key secondary endpoint.