A Randomized Open-Label Phase 2/3 Study of BT8009 as Monotherapy or in Combination in Participants with Locally Advanced or Metastatic Urothelial Cancer (Duravelo-2)

The purpose of this study aims to determine if BT8009, when given in combination with pembrolizumab, works against urothelial cancer. This will be compared to standard chemotherapy treatment followed by avelumab therapy. This research study also aims to understand the side effects of BT8009 when given in combination with pembrolizumab. The study drug BT8009 is investigational (i.e., experimental). An investigational drug is one that has not been approved by the Food and Drug Administration (FDA) to treat a certain condition or illness or a certain type of patient. Pembrolizumab is an antibody that is approved by the FDA in the United States Pembrolizumab is a type of therapy that works by blocking a protein called PD-1 to help prevent cancer cells from hiding and allows your immune system to detect and fight cancer cells. Gemcitabine, cisplatin, and carboplatin are chemotherapy agents that are approved by the FDA in the United States of urothelial cancer. These treatments disrupt DNA replication, which lowers cancer cells’ ability to divide and multiply. Avelumab is an antibody that was approved by the FDA in the United States for the treatment of urothelial cancer. Avelumab is a type of therapy that works by blocking a protein called PD-L1 to help prevent cancer cells from hiding and allows your immune system to detect and fight cancer cells. This study is being done to find answers to the following questions: • How your tumor responds to BT8009 given in combination with pembrolizumab or responds to other chemotherapy treatment. • What side effects occur with BT8009 given in combination with pembrolizumab. • If and how your general wellbeing (physical, emotional, and social) and daily activities change due to BT8009 in combination with pembrolizumab.

Are you Eligible? (Inclusion Criteria)

• Must be 18 years or older - Must have locally advanced urothelial cancer (tumor on your bladder, a portion of your kidney, your ureter or urethra which has grown, but is not removable by surgery but has not spread to other parts of the body) OR have Metastatic urothelial cancer(cancer has spread to other parts of the body). - Must not be pregnant - Must not have HIV