Dr D'Angelo on the Significance of Lete-Cel Treatment Across Sarcoma Subtypes

“The overall response rate at the primary analysis was 42%...and importantly, the responses do seem to be durable. These results are actually quite compelling when we put them into the context of current standard approved options for patients with synovial sarcoma and myxoid/round cell liposarcoma.”

Sandra P. D’Angelo, MD, medical oncologist, Memorial Sloan Kettering Cancer Center, discusses the significance of data from substudy 2 of the phase 2 IGNYTE-ESO trial (NCT03967223) evaluating letetresgene autoleucel (lete-cel) in synovial sarcoma (SyS) and myxoid/round cell liposarcoma (MRCLS).

Substudy 2 of the ongoing, international, open-label IGNYTE-ESO trial is investigating the efficacy and safety of lete-cel in treatment-naive and pretreated patients with NY-ESO-1–expressing advanced or metastatic SyS and MRCLS. A total of 64 patients were treated with lete-cel, 34 of whom had SyS and 30 of whom had MRCLS, D’Angelo details. The median age of the participants was 46 years, which aligns with the typical demographic for these sarcoma subtypes, she says, adding that the majority of enrolled patients (56%) were male.

Findings from the planned interim analysis revealed that among evaluable patients (n = 64), the overall response rate (ORR) was 42%, comprising 6 complete responses and 21 partial responses, D’Angelo reports. The response rates for both sarcoma subtypes were similar, with 41% and 43% of patients with SyS and MRCLS achieving a response, respectively.

Notably, the responses to lete-cel appeared to be durable, D’Angelo continues. The median duration of response (DOR) for the entire cohort was 12.2 months, with patients with SyS experiencing a longer median DOR at 18.3 months. Those with MRCLS had a median DOR of 12.2 months, she states. The median progression-free survival (PFS) was 5.3 months, D'Angelo notes.

Safety data were consistent with previous studies of lete-cel. All patients experienced treatment-emergent adverse effects, the most common of which were cytopenias, cytokine release syndrome, and rash. These toxicities were generally manageable and aligned with the known risk profile of the therapy.

The results of this substudy are compelling, particularly when considered alongside current standard treatment options for SyS and MRCLS, D’Angelo concludes.