Adaptimmune is moving closer to a second FDA approval for its T-cell receptor (TCR) T-cell therapy, Lete-cel, after promising results in a modified pivotal study, IGNYTE-ESO. The therapy targets the NY-ESO-1 tumor antigen and has shown efficacy in patients with advanced or metastatic synovial sarcoma or myxoid/round cell liposarcoma (MRCLS). This development builds on Adaptimmune's recent success with afami-cel, the first TCR-T cell therapy approved for solid tumors.
Clinical Efficacy of Lete-cel
The IGNYTE-ESO trial evaluated Lete-cel in 64 evaluable patients with NY-ESO-1-positive advanced sarcomas. The overall response rate was 42%, with six complete and 21 partial remissions observed. Specifically, in patients with synovial sarcoma, the response rate was 41% (14/34), while in MRCLS patients, it was 43% (13/30). The median duration of response was 12.2 months (95% CI 6.8, 19.5). In synovial sarcoma, the median duration of response was 18.3 months (95% CI 3.3, -), and in MRCLS, it was 12.2 months (95% CI 5.3, -). The median progression-free survival (PFS) was 5.3 months (95% CI 4.0, 8.0).
Safety Profile and Management
Common side effects associated with Lete-cel included cytopenias and cytokine release syndrome. These adverse events are typical for this class of drugs and were reported as manageable.
Regulatory Pathway and Market Context
Adaptimmune plans to submit a rolling Biologics License Application (BLA) to the US Food and Drug Administration (FDA) by the end of 2025, seeking approval for Lete-cel as a second-line TCR-T therapy for solid tumors. This follows the FDA's accelerated approval of Adaptimmune's afami-cel (afamitresgene autoleucel) in August for inoperable synovial sarcomas, which targets the MAGE-A4 antigen. The approval of afami-cel was based on response rate data, pending further clinical data confirmation.
Differentiating TCR-T Therapy
TCR-T cell therapies, unlike CAR-T cell therapies, can target peptide fragments from intracellular natural cancer antigens. This allows them to address a broader range of tumor-associated antigens. The process involves affinity-optimizing natural T cell receptors and transferring their genes into the patient's own CD8 or CD4 T cells, which are then expanded ex vivo.
Strategic Partnerships
Adaptimmune's ability to bring afami-cel to market and fund the IGNYTE-ESO trial was bolstered by a partnership with Galapagos NV, following Roche's withdrawal from a licensing agreement. Galapagos licensed uza-cel (Uzatresgene autoleucel), another TCR-T candidate targeting the MAGE-A4 antigen, for an upfront payment of US$100 million.
