Brief Summary
Researchers are looking for new ways to treat people with high-risk muscle-invasive urothelial carcinomacancer arising from tissues that line organs (MIUC). Urothelial carcinoma is a type of bladdera hollow, muscular sac in the pelvis that stores urine cancera disease where abnormal cells split without control and spread to other nearby body tissue and/or organs that begins in cellsthe basic structural and functional unit of all living things that line the inside of the bladder and other parts of the urinary tract, such as part of the kidneys, ureters, and urethrathe tube that carries urine from the bladder to outside of the body. People with MIUC usually have chemotherapya cancer treatment that uses drugs to kill or slow the growth of cancer cells, while minimising damage to healthy cells before surgerytreatment involving removal of cancerous tissue and/or tumours and a margin of healthy tissue around it to reduce recurrence, then surgery to remove the cancer. Chemotherapy is a type of medicine to destroy cancer cells or stop them from growing. After surgery, some people receive more treatment to prevent cancer from returning. Pembrolizumab is an immunotherapya treatment that uses a person's immune system to fight cancer, which is a treatment that helps the immune system fight cancer. Enfortumab vedotin (EV) is an antibodya protein made by the immune system to fight against harmful substances (antigens), such as bacteria or viruses drug conjugate (ADC). An ADC attaches to a protein on cancer cells and delivers treatment to destroy those cells. Researchers want to learn if giving V940 (the study treatment) with pembrolizumab can prevent MIUC from returning after surgery. V940 (also called mRNA-4157) is designed to treat each person’s cancer by helping the person’s immune system identify and kill cancer cells based on certain proteins found on those cancer cells.
The goals of this study are to learn if people who receive V940 and pembrolizumab are alive and cancer free longer than those who receive placebo and pembrolizumab, and to learn about the safety of V940, pembrolizumab, and EV, and if people tolerate them.
Intervention / Treatment
- Biological: Pembrolizumab
- Biological: V940
- Other: Placebo
- Biological: Enfortumab Vedotin
- Procedure: Surgery (RC plus PLND)
Inclusion Criteria
The main inclusion criteria include but are not limited to the following:
- Must provide bloodthe red bodily fluid that transports oxygen and other nutrients around the body samples per protocol, to enable V940 production, and circulating tumor deoxyribonucleic acid testing
- Has an Eastern Cooperative Oncologythe study, diagnosis and treatment of cancer Group performance status of 0 to 2 assessed within 7 days before randomization
- Must provide a formalin-fixed paraffin-embedded tumor tissuea group of cells that work together to perform a function sample for next generation sequencing
Adjuvant Cohort:
- Has MIUC
- Has dominant histology of urothelial carcinoma (UC)
- Has high-risk pathologic disease after radical resectionsurgical removal of tissue or part/all of an organ
- For participants who have not received cisplatin-based neoadjuvant chemotherapy, are ineligible to receive cisplatin according to protocol pre-defined criteria
Perioperative Cohort:
- Has MIBC
- Has a histological diagnosisthe process of identifying a disease based on signs and symptoms, patient history and medical test results of UC
- Is deemed eligible for RC and PLND and agrees to undergo curative intent standard RC and PLND and neoadjuvant and adjuvant treatment per protocol
- Is ineligible to receive cisplatin according to protocol pre-defined criteria