Clinical Trials | A Phase 1, Open-Label Study to Evaluate the Safety, Pharmacokinetics, and Pharmacodynamics of GB-4362 Administered with Enfortumab Vedotin and Pembrolizumab in Participants with Advanced Urothelial Cancer

The University of Virginia Comprehensive Cancer Center seeks participants ages 18 and over with locally advanced or metastatic urothelial cancer for a research study (cancer of the bladder or urinary tract). This study is testing an investigational medicine called GB-4362 given together with two approved cancer treatments, enfortumab vedotin (EV) and pembrolizumab. EV and pembrolizumab may be used together as standard treatment for your cancer. EV works by delivering an anti-cancer substance called MMAE directly into cancer cells. However, some MMAE can spread beyond the cancer cells and travel freely in the bloodstream. This is called “free MMAE”, and may contribute to side effects such as peripheral neuropathy (numbness, tingling, or pain in the hands and feet). GB-4362 is an investigational antibody designed to attach to the free MMAE in the blood. The main purpose of this study is to evaluate the safety and tolerability of GB-4362 and its effect on free MMAE levels. Researchers will also explore whether GB-4362 can help reduce certain side effects of EV- such as peripheral neuropathy. It is not known whether GB-4362 will provide any benefit. You May Be Able to Take Part If You: - Are 18 years of age or older - Have advanced or metastatic urothelial cancer - Are planning to receive EV and pembrolizumab as part of your cancer treatment - Are able to carry out daily activities with little or no assistance Some people who have already started EV and pembrolizumab may also qualify for the dose-escalation part of the study. You May Not Be Able to Take Part If You: - Have recently had certain other cancer treatments - Have uncontrolled diabetes - Have cancer that has spread to the brain and is not stable - Have had serious allergic reaction to an antibody medicine Other requirements apply. The study team will review whether this study is right for you. What to Expect This study has 2 parts: Dose Escalation and Dose Expansion. During dose escalation, the dose of GB-4362 is increased over time to find the preliminary recommended phase 2 dose. During dose expansion, additional participants will receive GB-4362 at the selected dose identified during dose escalation. Participation includes clinic visits for study treatment, blood tests, physical examination, and other study assessments. Your total time in the study will depend on which part of the study you join. Your study doctor will tell you whether you are participating in the Dose Escalation or the Dose Expansion part of the study, based on when you enroll. You will be followed for safety for approximately 18 weeks after your last dose of GB-4362, or until you start another anti-cancer treatment, whichever happens first. Taking part is completely voluntary, and you may leave the study at any time. GB-4362 and procedures performed only for research may be provided at no cost. The study team will explain which costs are covered by the study and which may be billed to your insurance. https://childrens.uvahealth.com/clinical-trials/trial/303341 NCT07484022