<h3>Purpose/Objective(s)</h3> Trimodality therapy (TMT) with maximal TURBT followed by chemoradiation (CRT) is a category 1 bladder preservation treatment option for patients with non-metastatic muscle invasive bladder cancer (MIBC). Radiation therapy increases PD-L1 expression in bladder cancer. This trial evaluates the activity of atezolizumab (atezo) in MIBC in combination with TMT. This trial was designed with pre-specified safety analyses of the first 80 patients (40 in each arm). The previous analyses did not show any significant increase in toxicity and DSMC recommended to proceed with further enrollment. This is the updated safety report of 213 patients. <h3>Materials/Methods</h3> This is a randomized phase III trial testing atezo every 3 weeks for 6 months given concurrently and adjuvantly with TMT vs. TMT alone in 432 eligible patients with MIBC (T2-T4aN0M0). Patients are stratified based on performance status; T2 vs T3 or T4; choice of chemotherapy; and radiation field (bladder only vs small pelvis). Patients undergo biopsy 3 months after finishing CRT to assess treatment response and are followed for 5 years for bladder intact event free survival. <h3>Results</h3> 100 patients were randomized to the TMT alone (control) arm and 113 patients to the TMT+ atezo arm. Patient characteristics for the atezo vs control arm are: Median age (75 vs 72), T2 (82% vs 81%), chemotherapy regimen: cisplatin (48% vs 50%), 5-fluorouracil/mitomycin (15% vs 13%), gemcitabine (37% vs 37%), radiation field including small pelvis (57% vs 58%), bladder only (43% vs 42%), performance status 0-1 (96% vs 95%). Two patients in each arm reported grade 3 diarrhea. Two patients had grade 3 cystitis in the atezo arm as compared to 1 patient in the control arm. Only 1 patient had treatment related grade 3 radiation cystitis confirmed by cystoscopy and biopsy and continued atezo without worsening of symptoms. Overall, 65 patients reported treatment related grade 3 or higher toxicity events in the atezo arm vs 44 in control arm (57% vs 44%). Most common toxicity was hematological (43% vs 36%) which was considered non-immune related. Other Grade 3 or higher known immune related AEs (irAE's) of atezo like pancreatitis (1), rash (1), acute kidney Injury (2), gastritis (1), transaminitis (1), & dyspnea (1) were observed in the atezo arm. Table1. <h3>Conclusion</h3> Toxicities observed were numerically higher in the atezo arm. One reason could be that more eligible patient data were available from the atezo arm (113 vs100). Most of them were hematological toxicities which did not require holding atezo and were considered non-immune related by the treating provider. Known irAE's were observed in the atezo arm. The trial is expected to finish accrual in next two years and this update demonstrates no safety concerns.