Phase I/II Study of the Safety, Pharmacokinetics, and Preliminary Clinical Activity of BT8009 in Patients with Nectin-4 Expressing Advanced Malignancies

BT8009 selectively binds to nectin-4. After internalization and proteolytic cleavage by peptidases that are upregulated in the tumor microenvironment (TME), MMAE binds to tubulin and inhibits its polymerization, which results in G2/M phase arrest and induces apoptosis in nectin-4 overexpressing tumor cells.

In this study, the sponsor and investigators want to learn:

• How much of the study drug alone and in combination with Pembrolizumab can be given with an acceptable level of side effects
• The effects of the study drug alone and in combination with Pembrolizumab (good and bad)
• How much of the study drug alone and in combination with Pembrolizumab is absorbed into the blood and how fast it is removed
• If research tests can be used in the future to predict who will benefit from BT8009 alone and in combination with Pembrolizumab
• How the study drug alone and in combination with Pembrolizumab acts in the body

This is a dose escalation/expansion study and will be conducted in four parts (Parts A, B, C, and D). In Part A of the study, the study will be evaluated alone and in combination with Pembrolizumab. Part A of the study is dose escalation, which means that the amount of study drug given will be increased in each group of research participants, to find the most appropriate dose for further study. In Part B, the dose expansion part of the study, a larger number of people will receive the study drug at the dose determined to be appropriate in Part A either alone or in combination with Pembrolizumab.

In Part C of the study, a small number of participants with kidney disease will receive the study drug alone at the dose determined to be appropriate in Part A.

In the fourth part (Part D) up to 10 participants with bladder, ovarian, breast or lung cancer will receive the study drug at a dose determined to be appropriate in Part A. Extra blood samples will be collected in this part to help the researchers better understand how the drug is processed by the body.

The study regimen will be given in cycles. You will receive the study drug as an IV infusion (intravenously, meaning the study drug will be given into a vein) given over 1 hour. If you are also receiving Pembrolizumab, it will be given as an IV infusion over 30 minutes. Participants will be given the study drug alone or in combination with Pembrolizumab at different times, called dosing schedules. Depending on the schedule you are enrolled on, you may receive the study drug alone or in combination with Pembrolizumab as follows:

• Schedule 1: Study drug alone every week on days 1, 8, 15, and 22 over a 4-week (28-day) cycle
• Schedule 2: Study drug alone every other week over a 4-week (28-day) cycle
• Schedule 3: Study drug every week on days 1 and 8 or days 1, 8, and 15 and with or without Pembrolizumab on day 1 over a 3-week (21-day) cycle

The dose and dosing schedule of the study you receive with or without Pembrolizumab will be determined when you enter the study. Your study doctor will explain which dosing schedule you will be on.