Preliminary results of bladder sparing by short-course radiotherapy combined with toripalimab in high-risk/extremely high-risk non-muscle invasive bladder cancer (HOPE-04).

e16557 Background: To evaluate the treatment safety and efficacy of short-course radiotherapy combined with PD-1 antibody (Toripalimab) as a potential bladder-preserving therapy for high-risk / extremely high risk non-muscle invasive bladder cancer (NMIBC). Methods: HOPE-04 is a single-arm open-label, phase II trial, which designs to evaluate the safety and efficacy of short-course radiotherapy (5 × 5 Gy) and Toripalimab as a novel bladder sparing treatment in patients with high-risk / extremely high risk NMIBC. Fifty-five pathological and imaging diagnosed NMIBC patients with or without BCG treatment will be recruited. Radiotherapy of 5× 5 Gy/fractions will be given to the whole bladder followed by a focal tumour bed boost and concomitant administration of Toripalimab of 240 mg intravenous infusion every 21 days for 12 cycles (about one year). The primary endpoints are disease free survival (DFS) and safety. The secondary endpoint is overall survival. Additional indicators include implementation rate of salvage surgery and quality of life. Results: Until now, 11 patients were included successfully, with 2 female patients and 9 male patients. And the median age was 62.36 years old. Of them, 5 patients were low grade differentiation, and 6 patients were high grade. The median follow-up time was 12.56 months. Two patients with history of multiple recurrence sites repeatedly suffered from local recurrence after radiotherapy and received radical cystectomy. The pathologic stagings were pT1N0 for both patients after surgery. Therefore, the one year- bladder intact DFS rate was 62.5% and the median RFS was not achieved. No patient died so far. For safety analysis, 4 patients suffered from immune-related adverse event, namely, grade 2 arthritis, grade 1 rash and grade 1 hyperthyroidism which led to treatment interruption of Toripalimab. And 2 patients experienced radiotherapy related toxicities, including grade 1 frequent urination and urgency, grade 1 erythra and grade 1 anal sagging sensation. No treatment related dose reduction happened. Conclusions: HOPE-04 is the first encouragement of short-course radiotherapy and Toripalimab combination in the treatment of high-risk / extremely high risk NMIBC, which extends the therapeutic options of bladder preservation treatment for this population. Our preliminary results show a promising effect both in prevention of local recurrence as well as distant metastasis, and toxicities were manageable, which would be verified by the final analysis. Clinical trial information: ChiCTR2200059970 .