Early experience with T-cell receptor cellular therapy in advanced solid malignancies: A multi-center analysis of safety and efficacy.

e14511 Background: T-cell receptor (TCR) therapy, by targeting intracellular antigens, represents a significant expansion of treatment options for solid tumours. We report the safety and preliminary efficacy from our early institutional experience using TCR therapy in a cohort of heavily pretreated patients with advanced solid malignancies. Methods: This multi-centre study included eight patients with advanced solid tumours. The primary endpoint was safety, assessed according to CTCAE v5.0, while secondary efficacy endpoints included objective response rate (ORR) and disease control rate (DCR) evaluated by RECIST v1.1. Survival outcomes were analysed using Kaplan-Meier methodology. Results: The cohort was extensively pretreated, with a median of 4 prior therapy lines (range: 3-5), and all patients had previously receivedimmunotherapy. Engineered TCRs targeted a range of intracellular antigens, including TP53 (n = 6), KRAS (n = 2), and CEA (n = 1). With a median follow-up of 9 months, the ORR was 50% (4/8 patients; 95% CI: 15.7-84.3%), consisting of four partial responses. A promising DCR of 75% was achieved (6/8 patients; 95% CI: 34.9-96.8%), with a median time-to-response of 2.0 months. Median event-free survival was 7 months, and median overall survival was not reached. The treatment was well-tolerated; only one patient (12.5%) experienced a grade 3 cytokine release syndrome, which was successfully managed. No immune-effector cell-associated neurotoxicity syndrome (ICANS) or other grade ≥3 adverse events were observed. Conclusions: In this heavily pretreated population, TCR-T cell therapy demonstrated significant anti-tumour activity and a favourable safetyprofile. These findings underscore the feasibility of this approach and warrant further investigation in larger clinical trials. Parameter Value Patients (N) 8 Median Age (range) 51 (29-67) Sex (Male/Female) 4 / 4 ECOG PS (0/1) 1 / 7 Median Prior Lines (range) 4 (3-5) Prior Immunotherapy 100% TCR Targets (TP53/KRAS/CEA) 6 / 2 / 1 Objective Response Rate (ORR) 50% (95% CI: 15.7-84.3) Disease Control Rate (DCR)Median Time-to-ResponseMedian Event-Free SurvivalMedian Overall SurvivalGrade ≥3 Adverse EventsGrade 3 CRSICANS 75% (95% CI: 34.9-96.8)2.0 months7 monthsNot Reached12.5%12.5% (1/8)0%