Lete-cel Study in Synovial Sarcoma, MRCLS Meets Primary Endpoint With 40% ORR

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Nine responses were ongoing as of the March 2023 cutoff date.

 Sandra P. D’Angelo, MD, oncologist, cellular therapist, and associate attending physician, Memorial Sloan Kettering Cancer Center

Sandra P. D’Angelo, MD

Credit: Memorial Sloan Kettering

IGNYTE-ESO (NCT03967223) sub study 2 evaluating letetresgene autoleucel (lete-cel; Adaptimmune) in patients with synovial sarcoma (SS) and myxoid/round cell liposarcoma (MRCLS) met its primary endpoint of safety and efficacy at a planned interim analysis, with a 40% overall response rate in evaluable participants.1

Data from the substudy were presented at the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting, held May 31 - June 4, in Chicago, Illinois, by Sandra P. D’Angelo, MD, sarcoma oncologist, cellular therapist, and associate attending physician, Memorial Sloan Kettering Cancer Center.

“[These data] support the potential of lete-cel as a novel therapy for patients with advanced or metastatic SS and MRCLS. The primary analyses will be presented late 2024 (sic). Further analyses of translational correlates are pending,” D’Angelo said during her presentation.1

Lete-cel is comprised of autologous CD4+ and CD8+ T-cells genetically engineered to express a T-cell receptor recognizing NY-ESO-1 peptide presented by HLA-A*2:01, A*2:05, or A*2:06.

READ MORE: Innovative Targets Enable Immunotherapy for Sarcomas

The study dosed 73 participants with human leukocyte antigen (HLA)-A*02:01, A*02:05, or A*02:06 and NY-ESO-1–expressing, unresectable or metastatic SS (n = 23; 51%) or MRCLS (n = 22; 49%). Participants received a median of 6.4 billion cells and 51% of patients received bridging therapy between leukapheresis and lymphodepletion.1

Eighteen of all 45 patients with at least 6 months of follow-up responded (40% [95% CI, 25.7-55.7]), with similar rates across patients with SS (39% [95% CI, 19.7-61.5) and MRCLS (41% 95% CI, 20.7-63.6]) and an 89% concordance between investigator- and independent-assessed response rates. One patient in each arm (SS and MRCLS) had a complete response. At the time of data cutoff, 9 responses were ongoing and median duration of response was 10.6 months (95% CI, 3.3-not estimable).1

"As the current treatment options in these 2 indications are significantly limited, both represent a greatly unmet medical need for novel, innovative therapies,” D’Angelo said in a statement.2

In the safety set of 73 participants, the findings were consistent with previous observations with lete-cel,. Most patients (93%) had a serious adverse event (AE); 83% had serious cytokine release syndrome (CRS). Grade 1 immune-effector cell associated neurotoxicity occurred in 3 (4%) patients and grade 3 rash occurred in 23 (32%) patients. Two patients (5%) experienced grade 5 AEs associated with lymphodepletion; these were neutropenia in the setting of pancytopenia that led to a fatal pulmonary infection, and pulmonary alveolar hemorrhage in the setting of pancytopenia and a platelet count of 0.1

"We're encouraged by the findings from the IGNYTE-ESO trial and the potential of our sarcoma franchise. Our lead cell therapy product, afami-cel, targets MAGE-A4 in synovial sarcoma and the ability to now also target the NY-ESO-1 cancer antigen with lete-cel will enable us to reach a greater number of people impacted by advanced sarcomas. We are eager to continue advancing lete-cel to further realize the promise of engineered TCR T-cell therapies for patients and healthcare providers... We continue to work toward commercializing afami-cel later this year and lete-cel in 2026,” Dennis Williams, PharmD, Senior Vice President, Late-Stage Development, Adaptimmune, added.2

REFERENCES
1. D’Angelo SP, Furness AJS, Thistlethwaite D, et al. Lete-cel in patients with synovial sarcoma or myxoid/round cell liposarcoma: Planned interim analysis of the pivotal IGNYTE-ESO trial. Presented at: 2024 (ASCO) Annual Meeting; May 31 - June 4; Chicago, Illinois. Abstract #2500
2. Adaptimmune to Present Data from Planned Interim Analysis of Pivotal IGNYTE-ESO Trial with Lete-cel at ASCO; Data Continue to Support further Development of Sarcoma Franchise. News release. Adaptimmune. June 3, 2024. https://www.adaptimmune.com/investors-and-media/news-center/press-releases/detail/270/adaptimmune-to-present-data-from-planned-interim-analysis
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