105P - Preliminary efficacy and safety results from ‘ReBirth’, a phase II study of risk-based bladder-sparing therapy for MIBC.

Background

Trimodal therapy (TMT) has achieved long-term survival and persistent oncologic control in selected MIBC patients, however, tailored treatment using biomarkers 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 is a two-stage, single-arm, phase II trial recruiting cT2-4aN0-1M0 MIBC pts. Based on results of cystoscopy, urine cytology, imaging and MRD detection after first stage (Tislelizumab (T) 200 mg on D1, Cisplatin (C) 70 mg/m² on D1 and Gemcitabine (G) 1000 mg/m² on D1 and D8 Q3W for 3-4 cycles), pts achieving cCR (cT0, cTa) are treated with T, while the other pts receive T and chemoradiotherapy (whole bladder 44Gy/16 fractionation combined with C as radiosensitizer). 1-year BIDFS rate is the primary endpoint. Secondary endpoints include 2-year MFS rate, 2-year BIDFS rate and safety. Tissue and urine samples will be obtained for genetic profiling and biomarker research.

Results

As of September 20, 2023 (follow up: 258 (49-415) days, 25 pts with a median age of 64 (36-77) yrs were enrolled and 96% are male. 19 pts with cT2 (57.14%), cT3 (33.33%) and cT4 (9.52%) tumors were evaluable. 2 pts were assessed as N1. 14/19 pts (73.68%) achieved cCR and maintained a sustained response. Based on positive urine cytology and MRD, 5 pts were classified as non-cCR (2 pts in cT3N0M0, 2 pts in cT4N0M0 and 1 pt in cT2N0M0). Due to RC (2 pts achieving ypT0N0 and 1 pt achieving ypT2N0) and incomplete treatment cycles, 6 pts were excluded from the efficacy analysis set. BFS rate at 1 yr is evaluated in 6 pts (2 pts received hypo-fractionated on the second stage) and the rate is 100%. TRAEs were found in 19 of 25 pts (76%, 8% are ≥ 3 grade). Hematological AEs (32%), renal insufficiency (24%), pruritus (20%), and fatigue (20%) are the most common AEs. During hypo-fractionated radiation, no new safety signs were discovered.

Conclusions

The preliminary findings indicate a potential efficacy and manageable toxicity during the two-stage treatment. Enrollment is still ongoing, and long-term efficacy will be proved.

Clinical trial identification

NCT05531123.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.