e16000 Background: There is no effective intravesical second-line therapy for high-grade non-muscle-invasive bladder cancer (HGNMIBC) when Bacillus Calmette-Guerin (BCG) fails. In this scenario, a new perspective is represented by OncoTherad immunomodulator. OncoTherad is a nanostructured inorganic phosphate complex associated to glycosidic protein, developed by University of Campinas/ Brazil, which exhibits antitumor properties. The aims of the study were to evaluate the efficacy and safety of OncoTherad immunomodulator for BCG-refractory or relapsed HGNMIBC. Methods: We carried out a prospective, single-center (Municipal Hospital of Paulinia, São Paulo, Brazil), single-arm phase I/II study in 15 (10 male, 5 female) consecutive patients with HGNMIBC-refractory or relapsed (≥ 1 previous course of BCG intravesical therapy). Patients with muscle-invasive disease were excluded. OncoTherad regimen consisted of an induction course of 6 weekly intravesical instillations followed by a maintenance course of 1 monthly instillation until completing 1 year of treatment. Follow-up was performed with systematic mapping biopsies of the bladder, cystoscopy, ultrasound and urinary cytology. The primary endpoint was recurrence-free survival (RFS) rate, and secondary endpoint was safety response. The recurrence was defined as histology proven tumor recurrence (any grade), and monitored at 3-month intervals. Results: The median age and follow-up were 71 years and 14.0 months, respectively. A 14-months RFS rate in all patients was 86.7%. Only 2 patients (13.3%) showed recurrence during follow-up, however these patients showed incipient malignant lesions (downstaging of pT1G3 to pTaG1). Regarding toxicity, we reported moderate adverse systemic event of hypersensitivity to OncoTherad in 2 patients (13.3%), and minimal local side effects (dysuria and cystitis)in 6 patients (40.0%). Conclusions: In conclusion, OncoTherad seems a safe and effective treatment option for BCG-refractory or relapsed HGNMIBC patients and may provide benefit for preventing tumor recurrence. We report a RFS rate of 86.7% (14.0 months), potentially avoiding or postponing the need for radical surgery in these patients. Clinical trial information: CAAE: 93619718.7.0000.5404.