Efficacy and safety of engineered TCR-T cell therapy (afami-cel, lete-cel) in pediatric synovial sarcoma.

11569 Background: Synovial sarcoma (SyS) represents ~ 5% of adult soft tissue sarcomas, however, SyS is the most common non-rhabdomyosarcoma soft tissue sarcoma in the pediatric population. Both lete-cel, an engineered TCR-T cell therapy targeting NY-ESO-1, and afami-cel, an engineered TCR-T cell therapy targeting MAGE-A4, have shown efficacy and an acceptable safety profile in adult patients with SyS. We report here the largest cohort of pediatric SyS patients treated with either afami-cel or lete-cel. Methods: Pediatric SyS patients (pts) were treated on four phase II trials: lete-cel SyS Pilot study (NCT01343043), lete-cel IGNYTE-ESO trial (NCT03967223), afami-cel SPEARHEAD-1 (NCT04044768) and SPEARHEAD-3 (NCT05642455). Initial data from SPEARHEAD-3 will be available and added at the time of presentation. Eligibility for this analysis: advanced (unresectable/metastatic) SyS, human leukocyte antigen (HLA)-A*02, NY-ESO-1 or MAGE-A4 expression, baseline ECOG 0–1 and received any dose of lete-cel or afami-cel as a single infusion. Key efficacy endpoints: independent review-assessed overall response rate (ORR) per RECIST v1.1, best overall response, duration of response (DoR). Key safety endpoints: adverse events (AEs), serious AEs, AEs of special interest (ex. Cytokine release syndrome (CRS)). Data is presented separately for lete-cel and afami-cel. Results: Seven pediatric pts (age 10 to 17) were treated with lete-cel for advanced disease. The median lete-cel dose was 4.9 x 10 9 transduced cells. The ORR was 43% (3/7 pts, 2 PR, 1 CR). The duration of response was 2.83, 7.39, and 7.39 months respectively; one response was ongoing at the time of this analysis. Pediatric pharmacokinetics and exposure-response data were in agreement with data from adult pts. Seven pediatric pts (age 13 to 16) were treated with afami-cel for advanced disease. The median afami-cel dose was 8.2 x 10 9 transduced cells. The ORR was 28.6% (2/7 pts, 2 PR). The duration of response was 4.7 and 17.4 months respectively; one response was ongoing at the time of this analysis. Similar pharmacokinetics were observed in pediatric pts compared to adult pts. CRS was common occurring in >50% of pts for both lete-cel and afami-cel; events were grade 1 or 2, except one patient with lete-cel experiencing grade 3 CRS. Cytopenias after lymphodepletion and T cell infusion were the most common grade 3 or 4 adverse events (>30% of pts) for both therapies. Conclusions: Engineered TCR-T cell therapy targeting NY-ESO-1 (lete-cel) or MAGE-A4 (afami-cel) has shown responses and durable responses in the pediatric SyS population. The safety profile in this age group is consistent with that observed in the adult population. TCR-T represents a potential new treatment paradigm for pediatric SyS patients. Further studies should help to determine the optimal timing for this cellular therapy. Additional Information: Coauthor Brian Van Tine, MD, died Nov 2025. Clinical trial information: NCT01343043 , NCT03967223 , NCT04044768 , NCT05642455 .