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

e16614 Background: Concurrent chemoradiotherapy (CRT) is a bladder-preserving option for patients (pts) with MIBC but is limited by systemic radiosensitizer toxicity from conventional chemotherapy agents. Novel agents with improved tolerability and efficacy are needed to be able to combine with RT. Sacituzumab govitecan (SG) is a Trop-2–directed antibody drug conjugate (ADC) with activity in metastatic urothelial carcinoma. RAD-SG is a single-arm phase I trial evaluating concurrent SG with adaptive radiation therapy (RT) in localized MIBC. Methods: Key eligibility include pts with MIBC (T2-T4aN0M0), including variant histology, ECOG PS Score 0-2, normal organ/marrow function, cr cl ≥ 30 mL/min, TURBT within ≤ 60 days prior to treatment. Pts with bilateral hydronephrosis and prior pelvic RT were excluded. Pts receive SG 7.5 mg/kg IV every 21d starting prior to RT then 2 cycles with concurrent adaptive RT over 6 wks (64 Gy) and undergo a mid-treatment cystoscopy evaluation. The primary endpoint is safety, tolerability, and feasibility of TMT with concurrent SG and adaptive RT. Secondary endpoints are bladder intact event-free survival (BI-EFS) defined as time from treatment to first occurrence of residual/recurrent MIBC, nodal or distant metastases, RC, or death from any cause. Correlative objectives include genetic and microenvironmental correlatives, characterization of tumor clonal dynamics, immune repertoire editing, and imaging changes following TMT. Planned enrollment is 20 pts. Results: The study has accrued 14/20 patients at Cleveland Clinic. Treatment was generally well tolerated with common grade 1–2 treatment-related adverse events (TRAEs) being alopecia (77%), anemia (69%), fatigue (62%), and lymphopenia (54%). Grade 3-4 TRAEs included lymphopenia (31%), anemia (8%), proteinuria (8%), and neutropenia (8%). DLT was seen in 2 pts, each with grade 3 neutropenia which recovered without G-CSF. No treatment-related deaths occurred. Four pts experienced recurrence; 2 required salvage RC and 1 developed metastatic disease. Enrollment is ongoing. Conclusions: SG with adaptive RT is feasible and safe in localized MIBC; efficacy and correlative analyses are ongoing. This is the first study to combine an ADC with RT in bladder cancer. Clinical trial information: NCT05833867 .