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Background Novel approaches are needed for patients with high-risk non-muscle invasive bladder cancer (NMIBC), due to high rates of recurrence even after treatment with standard therapies such as intravesical Bacillus Calmette-Guérin (BCG). Adoptive cell transfer with tumor infiltrating lymphocytes (TIL) has shown efficacy in malignancies such as melanoma, and preclinical data support this approach in bladder cancer. 1 2 Accrual has completed for a phase I clinical trial of intravesical autologous TIL therapy in patients with BCG-exposed NMIBC. Results for the primary objectives of safety and feasibility are reported, as well as short-term follow-up for secondary efficacy endpoints.Methods Patients with recurrent high-risk BCG-exposed NMIBC were enrolled prior to transurethral resection of bladder tumor (TURBT). TIL were harvested from the TURBT specimen and expanded. Patients underwent intravesical instillation with autologous TIL once weekly for four weeks. The primary objective was to assess the safety and feasibility of intravesical TIL therapy for NMIBC. Feasibility was defined as successful harvesting and rapid expansion of TIL product followed by intravesical delivery. Adverse events (AEs) were recorded to assess toxicity.Results Nine patients were enrolled in the trial and successfully completed therapy. Across all doses, the median percentage of cells delivered (defined as the proportion of total cells infused minus the number of cells recovered in the post-void urine) was 93.4% ( table 1). The treatments were well-tolerated with no related grade 3 or higher AEs. The most common AEs were fatigue and urinary symptoms including frequency. To date, seven patients have had at least one surveillance cystoscopy after completing treatment (figure 1). Of these, recurrence was observed in 5 patients. One patient elected to undergo radical cystectomy after recurrence and was found to have stage pTa disease. No patient experienced progression to muscle-invasive disease. Two patients have had a durable response with no evidence of recurrence during a mean follow-up of 14.5 (SD 7.6) months.Conclusions In this phase I trial, autologous intravesical TIL therapy was successfully completed in all nine participants, supporting the feasibility of this approach. No significant toxicity has been observed. Among seven patients evaluable for follow-up, a durable response has been observed for two participants, suggesting that a subset of patients may benefit from this therapy. Longer-term follow-up will provide additional data regarding potential clinical efficacy.Trial Registration ClinicalTrials.gov ID NCT05768347References Bunch BL, Morse J, Asby S, Blauvelt J, Aydin AM, Innamarato P, et al. Systemic and intravesical adoptive cell therapy of tumor-reactive T cells can decrease bladder tumor growth in vivo. J Immunother Cancer. 2020;8:e001673.Bazargan S, Bunch B, Ojwang‘ AME, Blauvelt J, Landin A, Ali J, et al. Targeting myeloid-derived suppressor cells with gemcitabine to enhance efficacy of adoptive cell therapy in bladder cancer. Front Immunol. 2023;14.Ethics Approval Participants gave informed consent to participate in this trial. This study was approved by the Moffitt Cancer Center Institutional Review Board (MCC# 21894).Abstract 1321 Figure 1Swimmer plot representing clinical follow-up for the study participantsAbstract 1321 Table 1Percentage of cells delivered per dose