Adaptimmune is moving closer to securing its second sarcoma approval as its investigational T cell therapy, lete-cel, demonstrated positive results in a Phase II trial. The UK-based company plans to submit a rolling Biologics License Application (BLA) to the US Food and Drug Administration (FDA) by the end of 2025 for lete-cel's use in treating advanced or metastatic synovial sarcoma and myxoid/round cell liposarcoma (MRCLS).
The pivotal Phase II IGNYTE-ESO trial (NCT03967223) evaluated the efficacy of lete-cel in patients with either synovial sarcoma or MRCLS. The primary analysis included data from 64 patients, revealing a 42% overall response rate. Specifically, patients with synovial sarcoma experienced a median response duration of 18.3 months, while those with MRCLS had a median response duration of 12.2 months. All patients experienced treatment-emergent adverse events (TEAEs), including cytopenia, cytokine release syndrome and rash. Adaptimmune noted that the safety profile was consistent with previous data, with no unexpected adverse events reported.
Addressing Unmet Needs in Sarcoma Treatment
Synovial sarcoma and MRCLS are rare and often aggressive cancers that present significant treatment challenges. Synovial sarcoma, a soft tissue cancer primarily affecting young adults, arises in the limbs. MRCLS, a subtype of liposarcoma, is known for its rapid spread and resistance to conventional treatments such as surgery, chemotherapy, and radiotherapy. The limited treatment options available underscore the urgent need for innovative therapies.
Expanding Adaptimmune's Sarcoma Portfolio
Adaptimmune achieved its first FDA approval in August 2024 for Tecelra (afami-cel), a T cell receptor (TCR) therapy indicated for adults with metastatic synovial sarcoma. This approval marked a significant milestone as the first engineered cell therapy for solid tumors and the first new therapy for synovial sarcoma in over a decade. According to a GlobalData analyst, the approval of lete-cel would multiply the US addressable market by 2.5 times, from 400 patients annually with Tecelra to 1,000. The treatments could be combined or administered sequentially, as lete-cel targets another antigen.
Strategic Partnerships and Future Directions
Adaptimmune has actively pursued partnerships to strengthen its position in the cell therapy landscape. While a previous collaboration with Roche's subsidiary Genentech on T cell therapy development was terminated, Adaptimmune quickly secured a $665 million deal with Galapagos for uza-cel, a MAGE-A4 T cell therapy. The company has also partnered with Agilent Technologies to develop the MAGE-A4 ICH 1F9 pharmDx companion diagnostic, which received FDA approval in August, and with Thermo Fisher Scientific to include Tecelra in the labeling for their SeCore CDx HLA-A Locus Sequencing System.
Detailed results from the IGNYTE-ESO trial are scheduled to be presented on November 16 at the Connective Tissue Oncology Society (CTOS) 2024 annual meeting in San Diego, US.
