Lete-cel (NY-ESO-1 TCR-T) and afami-cel (MAGE-A4 TCR-T) show ~29–43% ORR in pediatric metastatic synovial sarcoma

Lete-cel is an engineered autologous TCR-T targeting NY-ESO-1 and afami-cel is an engineered autologous TCR-T targeting MAGE-A4; this pooled pediatric analysis across four Phase II studies (NCT01343043, NCT03967223, NCT04044768, NCT05642455) enrolled advanced unresectable/metastatic, HLA-A*02+, antigen-expressing SyS with ECOG 0–1 treated as a single infusion. Lete-cel achieved an independent review ORR of 43% (3/7; 1 CR, 2 PR) with DoR 2.8–7.4 months (1 ongoing), while afami-cel achieved an ORR of 28.6% (2/7 PR) with DoR 4.7 and 17.4 months (1 ongoing); efficacy is in the ballpark of (or modestly above) typical cytotoxic salvage response rates reported in pediatric/AYA NRSTS regimens and later-line options, but cross-trial comparisons are very shaky given the tiny n and biomarker selection. CRS occurred in >50% with both products (mostly grade 1–2; one grade 3 CRS with lete-cel), and the most common grade 3/4 events were cytopenias post-lymphodepletion/T-cell infusion (>30%)—a toxicity pattern broadly consistent with engineered T-cell therapies rather than the chronic toxicities of multi-cycle chemo.