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Background Letetresgene autoleucel (lete-cel) is an investigational T-cell receptor therapy targeting the NY-ESO-1 cancer/testis antigen, which is highly expressed in synovial sarcoma (SyS) and myxoid (with or without round cell) liposarcoma (MRCLS). An integrated analysis of lete-cel efficacy and safety was conducted using pooled data from three single-arm trials of patients with advanced SyS and MRCLS.Methods The integrated efficacy and safety analysis included data from two pilot trials ( NCT01343043, NCT02992743) and the pivotal IGNYTE-ESO trial (NCT03967223), plus an ongoing long-term follow-up study (NCT03391778). Eligibility: previously treated advanced (unresectable/metastatic) SyS or MRCLS, human leukocyte antigen (HLA)-A*02:01, *02:05, or *02:06-positive, NY-ESO-1 expression, baseline ECOG 0–1, and received any dose of lete-cel. Treatment-naïve patients (SyS, n=5) were excluded from the efficacy analyses. Response was assessed by independent review in all three studies. Key efficacy endpoints: overall response rate (ORR) per RECIST v1.1, best overall response, duration of response (DoR), time to response, disease control rate, progression-free survival (PFS), overall survival (OS) and persistence. Key safety endpoints: adverse events (AEs), serious AEs, AEs of special interest, deaths, laboratory assessments, and replication competent lentivirus. Data was pooled and outputs present combined data and subgroup analyses summarized by indication and overall.Results A total of 178 sarcoma patients were enrolled, of which 147 received lete-cel and were included in the pooled safety population (97 [66.0%] with SyS, 50 [34.0%] with MRCLS) and 142 were evaluable for efficacy. At baseline in the overall population, median age was 40.0 years (range, 10–73), 44.4% were female, and 92.3% were White; baseline characteristics were similar across SyS and MRCLS. Independent reviewer-assessed ORR was 43.0% (61/142) overall, 45.7% (42/92) in SyS, and 38.0% (19/50) in MRCLS ( table 1). Median DoR and PFS in overall/SyS/MRCLS was 7.16/6.74/7.16 months and 5.29/4.04/7.69 months, respectively. Median OS was 20.50 months overall. The integrated safety analysis will be presented but to date, lete-cel treatment has a manageable safety profile consistent with T-cell therapy and lymphodepletion, including transient serious cytopenias, rash, and mild/moderate cytokine release syndrome.Conclusions The integrated analyses provide a comprehensive report of the efficacy and safety profile of lete-cel in the largest population to date. Efficacy as assessed by ORR, PFS, and OS was comparable across indications, further supporting the validity of lete-cel as an effective therapy for patients with advanced SyS and MRCLS.Acknowledgements This analysis was funded by Adaptimmune. Writing and editorial support was by Chloe Koulouris, PhD, of Envision Pharma, Inc. (Horsham, UK), funded by Adaptimmune.Trial Registration Lete-cel pilot trial in SyS (CT.gov, NCT01343043) Lete-cel pilot trial in MRCLS (CT.gov, NCT02992743) Lete-cel phase 2 IGNYTE-ESO (CT.gov NCT03391778)Ethics Approval This was a secondary analysis of existing clinical trial data and did not require ethical approval. Written informed consent was obtained from participants at the time each trial was conducted.Abstract 320 Table 1Integrated efficacy analysis outcomes from previously treated patients with SyS or MRCLS who received lete-cel treatment in interventional clinical trials (independent review)