3203 - CONSOLIDATE: Concurrent Radiotherapy with Enfortumab vedotin (EV) for Locally Advanced Bladder Cancer
Presenter(s)
P. P. Carriere1, J. Gao2, O. Alhalabi2, W. Qiao3, C. Lozano4, M. Campbell2, A. Y. Shah2, C. Kovitz2, S. Goswami2, M. Desai2, H. Mok1, C. Tang1, O. Mohamad1, L. L. Mayo1, K. Bree5, N. Navai5, B. Lee5, A. Kamat5, K. E. Hoffman1, S. Choi1, and C. J. Hassanzadeh1; 1Division of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, 2Department of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, 3Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, TX, 4Department of Genitourinary Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, 5Department of Urology, The University of Texas MD Anderson Cancer Center, Houston, TX
Purpose/Objective(s): Locally advanced muscle invasive bladder cancer (LA-BC) is currently treated with sequential lines of systemic therapy, with local therapies such as cystectomy rarely pursued. Bladder-preserving trimodality therapy (TMT), which integrates systemic therapy, radiotherapy (RT), and transurethral resection, has emerged as an alternative approach; however, this has classically been reserved for early stage MIBC patients. Radio-sensitizing cytotoxic chemotherapy has off target effects and has shown limited utility in LABC. Enfortumab vedotin (EV), an antibody-drug conjugate (ADC) targeting Nectin-4, has demonstrated promising activity in LABC, and pre-clinical models have shown synergy between ADCs and RT. This warrants investigation into a novel, treatment paradigm for patients with LABC. CONSOLIDATE is a single-arm phase I/II trial investigating concurrent EV with hypofractionated RT in patients with LA-MIBC.
Materials/Methods: This is an open-label, single-arm trial including patients with histologically confirmed urothelial carcinoma, LABC (T4N0 or T1-4N2-3). Patients with mixed urothelial histology are allowed. Eligibility criteria include ECOG 0-2, normal organ and marrow function with creatinine clearance = 30 mL/min. Patients should have received at least 2 cycles of EV prior to enrollment as a part of the consolidate RT strategy. Exclusion criteria include prior pelvic RT, distant metastases beyond regional lymph nodes, and active autoimmune disease precluding RT.
The phase I portion will determine the optimal concurrent EV dose, followed by a phase II expansion cohort. EV dosing will be investigated in the phase I lead-in with two dose levels. Dose level 1 will be 1mg/kg IV day 1 and 8 every 28 days, with a dose reduction to 0.75mg/kg if dose-limiting toxicity is encountered. RT is delivered concurrent with EV over 4 weeks to a dose of 55Gy in 20 fractions with optional lymph node coverage. RT techniques will include intensity-modulated RT (IMRT), or proton therapy with CT or MRI image-guidance. Post-RT maintenance EV is optional per physician discretion. Primary endpoints include safety/tolerability of this novel treatment approach, progression-free survival for concurrent EV and RT compared to historical controls with systemic therapy approaches, and health-related quality of life assess by EQ-5D-5L, EORTC MIBC module and EPIC bowel domain instruments. Secondary endpoints will include overall survival and metastasis free survival. Translational objectives include 1) investigating minimal residual disease detection assays prior to RT and post-RT, and 2) characterization of mechanisms that drive resistance to combined EV plus RT. The study aims to accrue up to 47 patients at MD Anderson Cancer Center and partner sites and enrollment is ongoing. Clinical trial information: NCT06434350. Research sponsor: Myriad Genetics.Results: TBD
Conclusion: TBD