Memorial Sloan Kettering Cancer Center
The researchers are doing this study to find out whether stereotactic body radiation therapy (SBRT) in combination with immunotherapy (cemiplimab with or without fianlimab) before cystectomy is an effective and safe treatment for people with muscle-invasive bladder cancer (MIBC).
Patients will be assigned to neoadjuvant SBRT and cemiplimab (Cohort 1) until Cohort 1 completes accrual and then enrollment for Cohort 2 will begin with those patients receiving neoadjuvant SBRT plus cemiplimab and fianlimab.
Inclusion Criteria: * Age ≥ 18 years at the time of informed consent * ECOG 0-1 * Histologically confirmed diagnosis of urothelial carcinoma. ° Variant histology is acceptable if there is a predominant urothelial component. Any neuroendocrine / small cell components are excluded (Investigators are encouraged to discuss with study team and PI) * Cystoscopically and radiographically confirmed cT2-4a cN0 cM0 disease per American Joint Committee on Cancer Staging Manual, 8th edition. * Patients with cT4a disease invading into the prostatic stroma with no cystoscopic confirmation of muscle i…
Stereotactic body radiotherapy (SBRT) Tumor-directed SBRT will be delivered in three once-daily 8 Gy fraction
Cemiplimab will be delivered on day 1 of each cycle for a total of 4 cycles,
Within 96 hours (i.e., 4 days) of completing the 3rd SBRT treatment, patients will receive their first cycle of cemiplimab and fianlimab in the morning or early afternoon. Patients will receive a total of 4 cycles of cemiplimab and fianlimab with each cycle lasting 3 weeks and treatment occurring during weeks 0, 3, 6, and 9. Cemiplimab and fianlimab infusions in the morning or early afternoon will be encouraged.
Within 60 days of completing the 4 cycles of cemiplimab and fianlimab, patients will undergo radical cystectomy which is standard of care.