216P - 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 muscle-invasive bladder cancer (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 urine minimal residual disease(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 bladder intact disease-free survival (BIDFS) rate is the primary endpoint. Secondary endpoints include 2-year metastasis free survival (MFS) rate, 2-year BIDFS rate and safety. Tissue and urine samples will be obtained for genetic profiling and biomarker research.

Results

As of August 15, 2023 (median follow up: 310 (217-377) days, 18 pts with a median age of 64.5 (41-77) years were enrolled and 94.44% are male. 15 pts with cT2 (55.55%), cT3 (33.33%) and cT4 (11.12%) tumors were evaluable. 2 pts were assessed as N1. 12/15 pts (80%) achieved cCR and maintained a sustained response. Based on positive urine cytology and urine MRD, 3 pts were classified as non-cCR (2 pts in cT3N0M0 and 1 pt in cT4N0M0). Due to RC (ypT0N0 and ypT2N0) and incomplete treatment cycles, 3 pts were excluded from the efficacy analysis set. TRAEs were found in 12 of 18 pts (66.67%). The only grade 3-4 TRAE observed (5.56%) was adrenal cortical insufficiency. Hematological AEs (22.22%), pruritus (22.22%), and fatigue (16.67%) 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.

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.