Adaptimmune Therapeutics plc (NASDAQ: ADAP) announced that its engineered cell therapy, letetresgene autoleucel (lete-cel), has received Breakthrough Therapy Designation from the U.S. Food and Drug Administration (FDA) for the treatment of patients with unresectable or metastatic myxoid/round cell liposarcoma (MRCLS). This designation is specifically for patients who have previously undergone anthracycline-based chemotherapy, are positive for HLA-A02:01, HLA-A02:05, or HLA-A*02:06, and whose tumors express the NY-ESO-1 antigen. The company plans to present further details at the Annual J.P. Morgan Healthcare Conference.
Clinical Efficacy in MRCLS
The Breakthrough Therapy Designation was based on data from the Phase II IGNYTE-ESO trial. In this study, 27 out of 64 patients (42%) with either synovial sarcoma or MRCLS showed RECISTv1.1 responses as assessed by independent review, including 6 complete responses and 21 partial responses. Specifically, in MRCLS patients, the response rate was 13 out of 30 (43%). The median duration of response (DoR) was 12.2 months (95% CI 6.8, 19.5) for the combined group and 12.2 months (95% CI 5.3, -) for MRCLS patients.
Safety Profile
The safety profile of lete-cel in the IGNYTE-ESO trial was consistent with previous data. All patients experienced treatment-emergent adverse events, with cytopenias, cytokine release syndrome (CRS), and rash being the most common. Overall, the toxicities were manageable, supporting an acceptable benefit-to-risk profile.
Regulatory and Development Plans
The Breakthrough Therapy Designation is intended to accelerate the development and review of drugs that demonstrate substantial improvement over existing therapies on a clinically significant endpoint. With this designation, Adaptimmune anticipates benefits such as more frequent interactions with the FDA, a rolling submission of the Biologics License Application (BLA), and potential priority review. Adaptimmune plans to initiate a rolling BLA submission for lete-cel later this year, targeting a market launch in 2026 for both synovial sarcoma and MRCLS indications.
Executive Commentary
Adrian Rawcliffe, Adaptimmune's Chief Executive Officer, stated, "This designation by the FDA highlights the potential of lete-cel to address a critical need for new treatment options for patients with MRCLS. This is another important milestone in building out our sarcoma franchise, as we aim to bring lete-cel to market in 2026 for the treatment of synovial sarcoma and MRCLS."
About Adaptimmune
Adaptimmune is a fully integrated cell therapy company focused on redefining cancer treatment through its engineered T cell receptor (TCR) platform. The company develops personalized medicines designed to target and destroy difficult-to-treat solid tumor cancers.
