Updated efficacy and safety results from ReBirth, a phase II study of risk-based bladder-sparing therapy for MIBC.

4586 Background: Trimodal therapy (TMT) has achieved long-term survival and persistent oncologic control in selected MIBC patients, however, tailored treatment based on chemotherapy plus PD-1 inhibitor responses is currently absent. Furthermore, the safety and efficacy of hypo-fractionated radiation in combination with PD-1 inhibitors and concurrent chemotherapy is worth exploring. Methods: This was a two-stage, single-arm, phase II trial recruiting cT2-4aN0-1M0 MIBC pts. Based on results of cystoscopy, urine cytology and imaging after first stage (Tislelizumab (T) 200 mg on D1, Cisplatin (C) 70 mg/m 2 on D1 and Gemcitabine (G) 1000 mg/m 2 on D1 and D8 Q3W for 3-4 cycles), pts achieving cCR (cT0, cTa) were treated with T, while the other pts received T and chemoradiotherapy (whole bladder 44Gy/16 fractionation combined with C as radiosensitizer, if lymph node was positive, it could be dosed to the maximum tolerable dose, such as tumor boost 11Gy/4 fractionation). The primary endpoint was 1-year bladder-intact event-free survival (BI-EFS) rate in the intention to treat (ITT) population (from enrolment to muscle-invasive recurrence, nodal or distant metastasis, radical cystectomy (RC) or death). Secondary endpoints included 1-year BI-EFS rate in the per-protocol (PP) population, metastasis-free survival, recurrence-free survival and safety. Results: As of January 16, 2025 (median follow up: 14.3 months), 32 pts with a median age of 64 (36-79) years were enrolled (cT2: 71.8%; cT3: 21.9%; cT4: 6.3%; cN1: 6.3%). One pt withdrew consent and were not evaluated for efficacy. In the ITT population, 22 (71.0%) pts achieved cCR and 9 (29.0%) pts were non-cCR. Four pts underwent RC before finishing the first-stage treatment. 1-year BI-EFS rate was 86.9% (95%CI, 68.8-94.9) in the ITT population and 95.8% (95%CI, 73.9-99.4) in the PP population. In the PP population, 1-year BI-EFS rate for cCR pts and non-cCR pts was 100% and 80% respectively. Overall, 5 pts had T1HG recurrence. Meanwhile, 3 pts developed distant metastases (Bone:3; distant lymph node:2). TRAEs of any grade were found in 78.1% pts and 42.3% experienced grade 3-4 TRAEs. No new safety signs were discovered. Conclusions: The updated findings continued to show promising efficacy and manageable toxicity via the two-stage treatment. Non-cCR pts might avoid RC through intensified treatment with chemoradiotherapy and T. Follow-up for long-term survival outcomes is still ongoing. Clinical trial information: NCT05531123 .