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Tremelimumab Shows Potential Among Patients With PD-1/PD-L1–Resistant Metastatic Urothelial Cancer
According to a phase 2 study, a high dose of tremelimumab showed modest activity and similar toxicity as previously reported among patients with PD-1/PD-L1–resistant metastatic urothelial cancer.
Eric J. Miller, MD, Tisch Cancer Institute at Icahn School of Medicine, New York, New York, and coauthors wrote, “Single-agent cytotoxic T-lymphocyte–associated protein 4 (CTLA-4) blockade in metastatic urothelial cancer has been underexplored.” They also noted that in previous trials evaluating tremelimumab among PD-1/PD-L1 naïve patients with metastatic urothelial cancer, the activity was comparable with PD-1/PD-L1 blockade, “raising the hypothesis that these classes of immune checkpoint inhibitors might be non-cross-resistant.”
In this phase 2 trial, 26 patients with metastatic urothelial cancer who had been treated with PD-1/PD-L1 blocked received 750 mg single-agent tremelimumab every 28 days for up to 7 cycles. The primary end point was objective response rate (ORR).
There was a total of 24 patients evaluable for response. There were 2 partial responses, lasting 10.9 months and 24.0 months, for an ORR of 8.3%. Additionally, 20.8% of patients achieved stable disease, with a median duration of stable disease of 5.4 months. The most common adverse events were diarrhea (58%), elevated hepatic transaminases (27%), and adrenal insufficiency (8%). There was 1 death, due to immune-related hepatitis.
Dr Miller et al concluded, “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.”
Source:
Miller EJ, Rose TL, Maughan BL, et al. Phase 2 trial of tremelimumab in patients with metastatic urothelial cancer previously treated with programmed death 1/programmed death ligand 1 blockade. Cancer. Published online January 5, 2024. doi:10.1002/cncr.35179
