AdAPT-001, EpicentRx's Oncolytic Virus-Delivered TGFβ Inhibitor, Receives FDA Fast Track Designation for Soft Tissue Sarcoma
Key Insights
The FDA has granted Fast Track designation to EpicentRx (search)'s AdAPT-001 for treating recurrent or refractory soft tissue sarcoma (search) (STS).
AdAPT-001, delivered via an oncolytic adenovirus, inhibits transforming growth factor beta (TGFβ (search)) and is used with nivolumab or atezolizumab.
The Fast Track designation is supported by Phase 1 and 2 trial data, showing promising activity and safety, with progression-free survival of ~8.5 months.
EpicentRx (search) announced that the U.S. Food and Drug Administration (FDA) has granted Fast Track designation to AdAPT-001, an oncolytic adenovirus-delivered transforming growth factor beta (TGFβ (search)) inhibitor, in combination with anti-PD-1 (nivolumab) or anti-PD-L1 (atezolizumab) for the treatment of recurrent or refractory advanced or metastatic soft tissue sarcoma (search) (STS). This designation aims to expedite the development and review of AdAPT-001 for STS, a rare and heterogeneous tumor type characterized by poor prognosis and limited treatment options.
The Fast Track designation is based on the potential of AdAPT-001 to enhance the sensitivity of STS tumors to checkpoint inhibitors. These tumors often exhibit low tumor mutation burden (TMB) and T-cell inflamed gene expression profiles (GEP), leading to non-response to checkpoint inhibitors. Clinical data from Phase 1 and 2 trials, along with an ASCO presentation, demonstrated the activity, safety, and durability of response, with a progression-free survival of approximately 8.5 months in STS patients treated with AdAPT-001, either alone or in combination with checkpoint inhibitors.
Mechanism of Action
AdAPT-001 is designed to address two key factors limiting the efficacy of checkpoint blockade immunotherapies: the absence of an immune infiltrate and the overexpression of immunosuppressive factors like TGFβ (search). The oncolytic virus delivers a TGFβ inhibitor directly to the tumor microenvironment, neutralizing TGFβ, decreasing Treg cell function, and promoting an inflamed tumor microenvironment. This dual mechanism aims to enhance the effectiveness of checkpoint inhibitors in STS and other tumor types.
Clinical Significance
According to EpicentRx (search) CEO and viro-oncologist, Dr. Tony Reid, MD, PhD, "Checkpoint blockade immunotherapies have revolutionized cancer therapy for many patients and prolonged the lives of millions. But efficacy depends on 1) the presence of an immune infiltrate, which is often absent or immunosuppressive, and 2) low levels of immunosuppressive factors like TGFβ (search), which are frequently overexpressed. AdAPT-001 is designed both to inflame the tumor microenvironment and to combat immunosuppression by neutralization of TGFβ through the expression of a TGFβ trap. Fast Track designation is a terrific acknowledgement of the potential of AdAPT-001 to make a meaningful difference for STS patients who desperately require new treatment options."
About AdAPT-001
AdAPT-001 is EpicentRx (search)'s proprietary 2-in-1 biologic designed to express a potent TGFβR inhibitor for local TGFβ (search) neutralization. This leads to decreased Treg cell function and improved therapeutic responses when combined with checkpoint inhibitors. It is being investigated in several tumor types, including STS, colorectal cancer, breast cancer, and hepatocellular carcinoma.