Adaptimmune Therapeutics has announced positive primary findings from its pivotal Phase II IGNYTE-ESO study, revealing that its investigational T cell therapy, lete-cel, induced significant treatment responses in patients with advanced or metastatic synovial sarcoma and myxoid/round cell liposarcoma (MRCLS). These results pave the way for a Biologics License Application (BLA) submission to the FDA by the end of 2025.
IGNYTE-ESO Trial Results
The IGNYTE-ESO trial, involving 64 treated patients, demonstrated a 42% overall response rate to lete-cel. This included six patients achieving complete response and 21 experiencing partial response. The median duration of response was 18.3 months in synovial sarcoma and 12.2 months in MRCLS. Progression-free survival was 5.3 months in the overall study sample.
According to Adaptimmune, the safety profile of lete-cel was consistent with previous studies, with manageable adverse events such as rashes, cytopenia, and cytokine release syndrome. The company considers the benefit-to-risk profile of lete-cel to be acceptable.
Regulatory and Commercial Strategy
"These data underscore lete-cel’s potential to transform the lives of people with these cancers who have a poor prognosis and few treatment options," said Adaptimmune CMO Elliot Norry. The company is preparing for a rolling BLA submission to the FDA for lete-cel in synovial sarcoma and MRCLS.
To support the regulatory process and potential commercialization, Adaptimmune is implementing a reprioritization initiative, including a 33% workforce reduction, aiming to reduce operating expenses by 25% in the first year. This cost-cutting campaign is projected to generate approximately $300 million in savings from 2025 to 2028, allowing Adaptimmune to focus on R&D programs with the highest potential return and patient benefit. Enrollment into the Phase II SURPASS-3 study of uza-cel for platinum-resistant ovarian cancer will be terminated as part of this initiative.
Market Impact and Existing Portfolio
Adaptimmune gained FDA approval for Tecelra (afamitresgene autoleucel) in August 2024 for unresectable or metastatic synovial sarcoma, marking the first engineered cell therapy approved for solid tumors and the first new treatment for synovial sarcoma in over a decade. CEO Adrian Rawcliffe noted the encouraging launch of Tecelra, with nine active treatment centers and one patient already undergoing apheresis in the third quarter. Adaptimmune projects peak sales of $400 million for Tecelra and lete-cel, pending the latter’s approval.
Sarcoma Treatment Landscape
Synovial sarcoma and MRCLS are rare and aggressive cancers with limited treatment options. Synovial sarcoma primarily affects young adults, while MRCLS is a subtype of liposarcoma known for its rapid spread and resistance to conventional treatments like surgery, chemotherapy, and radiotherapy. The potential approval of lete-cel could significantly expand the treatment options for these patients.
