Phase 2 trial of tremelimumab in patients with metastatic urothelial cancer previously treated with programmed death 1/programmed death ligand 1 blockade

Abstract Introduction Programmed death 1 (PD‐1)/programmed death ligand 1 (PD‐L1) blockade has changed the landscape of treatment for metastatic urothelial cancer, but single‐agent cytotoxic T‐lymphocyte–associated protein 4 (CTLA‐4) blockade in metastatic urothelial cancer has been underexplored. A prior phase 2 trial of tremelimumab in PD‐1/PD‐L1–blockade naive patients with metastatic urothelial cancer revealed activity comparable to that observed with PD‐1/PD‐L1 blockade raising the hypothesis that these classes of immune checkpoint inhibitors might be non‐cross‐resistant. Methods The current phase 2 trial treated patients with PD‐1/PD‐L1 blockade‐resistant metastatic urothelial cancer with single‐agent tremelimumab (750 mg intravenously every 28 days for up to 7 cycles). The primary end point was objective response rate. Results Twenty‐six patients were enrolled and 24 patients were evaluable for response. The objective response rate was 8.3%, composed of a total of two partial responses that lasted 10.9 and 24.0 months. Stable disease was observed in another 20.8% of patients, with a median duration of stable disease of 5.4 months. Diarrhea occurred in 15 patients (58%), elevated hepatic transaminases occurred in seven patients (27%), and adrenal insufficiency occurred in two patients (8%); one patient died after experiencing immune‐related hepatitis. Conclusions High dose CTLA‐4 blockade in patients with PD‐1/PD‐L1–resistant metastatic urothelial cancer has modest activity and is associated with treatment‐related toxicity similar to prior reports.