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- Title
Phase 2 trial of tremelimumab in patients with metastatic urothelial cancer previously treated with programmed death 1/programmed death ligand 1 blockade.
- Authors
Miller, Eric J.; Rose, Tracy L.; Maughan, Benjamin L.; Milowsky, Matthew I.; Bilen, Mehmet A.; Carthon, Bradley C.; Gao, Xin; Rapisuwon, Suthee; Zhao, Qianqian; Yu, Menggang; Agarwal, Neeraj; Galsky, Matthew D.
- 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. The current phase 2 trial sought to test that cytotoxic T‐lymphocyte–associated protein 4 blockade demonstrates anticancer activity in patients with metastatic urothelial cancer and is non‐cross‐resistant with programmed death 1 (PD‐1)/programmed death ligand 1 (PD‐L1) blockade. Tremelimumab in patients with PD‐1/PD‐L1–resistant metastatic urothelial cancer demonstrated modest activity and is associated with treatment‐related toxicity similar to prior reports.
- Subjects
TRANSITIONAL cell carcinoma; METASTASIS; IMMUNE checkpoint inhibitors; ADRENAL insufficiency; PROGRAMMED cell death 1 receptors
- Publication
Cancer (0008543X), 2024, Vol 130, Issue 9, p1642
- ISSN
0008-543X
- Publication type
Article
- DOI
10.1002/cncr.35179