TRACON Pharmaceuticals Inc (NASDAQ:TCON) said the US Food and Drug Administration (FDA) has approved its Investigational New Drug (IND) application for the initiation of a phase one-two clinical trial of YH001 in combination with envafolimab and doxorubicin for the treatment of sarcoma, including in patients who have not received prior therapy.
The trial will assess the safety and efficacy of YH001 and envafolimab in patients with the rare sarcoma subtypes of alveolar soft part sarcoma and chondrosarcoma.
Additionally, the safety and efficacy of the combination of YH001, envafolimab and doxorubicin will be assessed in the more prevalent sarcoma subtypes of leiomyosarcoma and dedifferentiated liposarcoma.
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TRACON CEO Charles Theuer said the company is pleased about the approval to initiate the triple combination trial, which includes the CTLA-4 antibody YH001, and the only subcutaneous checkpoint inhibitor approved anywhere in the world, envafolimab.
“We look forward to enrolling patients in this trial and giving patients additional options for their sarcoma treatment,” Theuer said in a statement.
YH001 is an IgG1 antibody against cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), which downregulates immune responses, particularly in cancers. YH001 was invented by Biocytogen, the parent company of Eucure Biopharma, and licensed by TRACON. It has shown enhanced antibody dependent cellular cytotoxicity (ADCC) and complement dependent cytotoxicity (CDC) in vitro.
In preclinical studies YH001 demonstrated superior T cell activation and superior tumor growth inhibition activity compared to ipilimumab. YH001 also demonstrated superior activity compared to ipilimumab in human transgenic mouse tumor models when combined with a PD-(L)1 antibody.
In these models, single agent YH001 depleted regulatory T cells and increased CD8+ T cells in tumor tissue. YH001 has been dosed as a single agent in a phase one trial in China (NCT04699929) and in combination with the PD-1 antibody toripalimab in a phase one trial in Australia (NCT04357756).
TRACON’s phase one-two clinical trial is a multicenter, open label study of YH001 initially given in combination with envafolimab, and then given in combination with envafolimab plus doxorubicin in patients with advanced or metastatic sarcoma, followed by phase two cohorts of patients with select histologies of advanced or metastatic sarcoma, including treatment naive patients.
The primary objective of the phase one portion of the trial is to determine the recommended phase two dose of YH001 in combination with envafolimab and in combination with envafolimab with doxorubicin. The primary objective of the phase two portion is to determine the objective response rate (ORR) of the combination of YH001 and envafolimab in patients with alveolar soft part sarcoma and chondrosarcoma and the ORR of the combination of YH001, envafolimab and doxorubicin in patients with leiomyosarcoma and dedifferentiated liposarcoma.
TRACON is a clinical-stage biopharmaceutical company using a cost-efficient, CRO-independent, product development platform to advance its pipeline of novel targeted cancer therapeutics and to form partnerships with other life science companies.
Contact the author at susie@proactiveinvestors.com