FDA Grants Fast Track to EpicentRx's AdAPT-001 for Recurrent/Refractory Soft Tissue Sarcoma

EpicentRx, a biopharmaceutical company based in La Jolla, California, announced that it has received Fast Track designation from the U.S. Food and Drug Administration (FDA) for its oncolytic adenovirus-delivered transforming growth factor beta (TGFβ) inhibitor, AdAPT-001. This designation is for the combination treatment of AdAPT-001 with the anti-PD-1 therapy nivolumab or the anti-PD-L1 therapy atezolizumab. The treatment is aimed at recurrent or refractory advanced or metastatic soft tissue sarcoma (STS) in patients who have experienced disease progression after undergoing at least one prior line of therapy.

The FDA’s Fast Track designation is designed to expedite the development and review process for drugs that address serious conditions or fulfill unmet medical needs. In the case of AdAPT-001, the designation is significant as it targets STS—a rare tumor type known for its high variability, resistance to conventional therapies such as chemotherapy, radiotherapy, and immunotherapy, and generally poor prognosis.

The decision to grant Fast Track designation to AdAPT-001 was influenced by its potential to make otherwise resistant STS tumors more responsive to checkpoint inhibitors like nivolumab and atezolizumab. This is crucial as these tumors often exhibit low levels of tumor mutation burden (TMB) and T-cell inflamed gene expression profiles (GEP), factors that typically predict non-responsiveness to such treatments. Evidence supporting the effectiveness of AdAPT-001 came from Phase 1 and 2 clinical trials, as well as a presentation at the American Society of Clinical Oncology (ASCO) conference, where the therapy demonstrated promising activity, safety, and a durable response with an average progression-free survival of approximately 8.5 months in patients with STS and other types of tumors.

Dr. Tony Reid, MD, PhD, and CEO of EpicentRx, explained the importance of checkpoint blockade immunotherapies in modern cancer treatment. He noted that the efficacy of these therapies is contingent upon the presence of an immune infiltrate, which is often lacking or suppressed in STS tumors. Additionally, the overexpression of immunosuppressive factors such as TGFβ limits the effectiveness of these treatments. AdAPT-001 is engineered to inflame the tumor microenvironment and to mitigate immunosuppression by neutralizing TGFβ through the expression of a TGFβ trap. According to Dr. Reid, the Fast Track designation is a significant recognition of AdAPT-001's potential to provide new, effective treatment options for patients with STS.

AdAPT-001 stands as EpicentRx's leading biologic therapy, designed to express a powerful TGFβR inhibitor that neutralizes local TGFβ, reduces Treg cell function, and enhances therapeutic responses when used in combination with checkpoint inhibitors. Its efficacy was highlighted during the 2024 ASCO conference for its potential in treating not just STS, but also colorectal cancer, breast cancer, and hepatocellular carcinoma.

EpicentRx is a privately-held firm with two main therapies that have received Fast Track status: AdAPT-001 and RRx-001 (nibrozetone), a small molecule radiochemoprotector. Both therapies are in late-stage clinical trials for their respective indications. RRx-001 is being investigated for severe oral mucositis and endometriosis, and has also garnered several grants to explore its antioxidant and anti-inflammatory properties in neurodegenerative diseases, such as Parkinson’s and ALS/MND, as well as in neurotoxic exposure scenarios.

Overall, the Fast Track designation for AdAPT-001 underscores its potential to address significant challenges in treating STS, offering hope for new, effective therapeutic strategies for patients in dire need of better treatment options.