RAD-SG: Adaptive radiation therapy with concurrent sacituzumab govitecan (SG) for bladder preservation in patients (pts) with muscle invasive bladder cancer (MIBC).

TPS896 Background: Concurrent chemoradiotherapy (CRT) is a recommended treatment option for pts with MIBC interested in bladder-preservation and/or not candidates for radical cystectomy (RC). Systemic radio-sensitizing chemotherapy may have off target side effects and exploring novel agents with radiation is an unmet need. SG is an antibody drug conjugate (ADC) and has shown efficacy in metastatic urothelial cancer (UC). RAD-SG is a single-arm phase 1 trial investigating the concurrent administration of SG with adaptive radiotherapy (RT) in pts with MIBC. Methods: Eligibility criteria include pts with localized MIBC (T2-T4aN0M0), ECOG PS Score of 0-2, normal organ and marrow function including creatinine clearance ≥ 30 mL/min, must undergo a TURBT within ≤ 60 days prior to treatment. Variant subtypes are allowed. Pts must not have had UC or any histological variant at any site outside of bladder within 24 months except Ta/T1/Carcinoma in situ (CIS) of the upper urinary tract including renal, pelvis, and ureter if underwent complete nephroureterectomy. Other exclusion criteria include bilateral hydronephrosis and prior pelvic / local RT for MIBC or any other cancer type. SG targets TROP-2, a surface protein expressed in UC, it will be given IV at 7.5 mg/kg every 21days starting prior to RT and 2 subsequent cycles with concurrent adaptive RT over a period of 6 weeks (64 Gy). The primary endpoint is safety, tolerability, and feasibility of trimodality therapy with concurrent SG and adaptive image-guided radiation therapy for patients with localized MIBC. The secondary endpoints are bladder intact event-free survival (BI-EFS) with concurrent SG and RT for MIBC and compare historical controls with other concurrent CRT regimens. BI-EFS is defined as the time from treatment to the first documented occurrence of residual/recurrent MIBC, nodal or distant metastases on imaging, RC, or death from any cause. Correlative objectives include 1) elucidation of the genetic and microenvironmental mechanisms that drive efficacy and resistance to combined ADC plus RT and 2) characterization of tumor clonal dynamics, immune repertoire editing, and imaging changes following treatment with SG plus RT. The study will accrue 20 pts at Cleveland Clinic Foundation and enrollment is ongoing. (NCT05833867). Clinical trial information: NCT05833867 .