Durvalumab is a selective, high affinity, engineered human IgG1 monoclonal antibody that blocks programmed cell death ligand-1 (PD-L1) binding to PD- and CD80. Tremelimumab is a human IgG2 antibody directed against CTLA4. Studies in other tumor types of platinum-based chemotherapy combined with immunotherapy have yielded improved efficacy with acceptable safety, and support exploration of this approach for locally advanced or metastatic urothelial carcinoma.
The presented study is a randomized, open-label, controlled, multicenter, global phase 3 study to determine the efficacy and safety of combining Durvalumab +/- tremelimumab with 6 cycles of standard of care chemotherapy (cisplatin + gemcitabine or carboplatin+ gemcitabine), followed by durvalumab monotherapy vs. standard of care alone as chemotherapy in patients with histologically or cytologically documented, unresectable, locally advanced, or metastatic transitional cell carcinoma of the urothelium (NCT03682068) (Figure 1).
Figure 1 – Trial design:
The primary outcome is efficacy in terms of progression-free survival and overall survival. Inclusion and exclusion criteria are shown in figure 2.
Figure 2 – Inclusion and exclusion criteria:
Presented by: Matt Galsky, MD, FASCO, Mount Sinai Medical Center, New York, NY
Written By: Hanan Goldberg, MD, Urologic Oncology Fellow (SUO), University of Toronto, Princess Margaret Cancer Centre, @GoldbergHanan at the 2019 American Society of Clinical Oncology Genitourinary Cancers Symposium, (ASCO GU) #GU19, February 14-16, 2019 - San Francisco, CA