NCT06305767

A Clinical Study of Intismeran Autogene (V940) Treatment and Pembrolizumab in People With Bladder Cancer (V940-005/INTerpath-005)

A Phase 1/2 Study of V940 Plus Pembrolizumab With or Without Enfortumab Vedotin in Muscle-Invasive Urothelial Carcinoma (MIUC) (INTerpath-005)

• Status: Active Not Recruiting
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 230 (estimated)
• Sponsor: Merck Sharp & Dohme LLC · Industry
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

Researchers are looking for new ways to treat people with high-risk muscle-invasive urothelial carcinoma (MIUC). Urothelial carcinoma is a type of bladder cancer that begins in cells that line the inside of the bladder and other parts of the urinary tract, such as part of the kidneys, ureters, and urethra. People with MIUC usually have chemotherapy before surgery, 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 immunotherapy, which is a treatment that helps the immune system fight cancer. Enfortumab vedotin (EV) is an antibody 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 intismeran autogene (the study treatment) with pembrolizumab can prevent MIUC from returning after surgery. Intismeran autogene (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 intismeran autogene and pembrolizumab are alive and cancer free longer than those who receive placebo and pembrolizumab, and to learn about the safety of intismeran autogene, pembrolizumab, and EV, and if people tolerate them.

Detailed description

Enrollment of participants into the Phase 1 Perioperative Cohort of this study is planned to start in approximately April of 2025.

Conditions

• Bladder Cancer

Interventions

Type	Name	Description
BIOLOGICAL	Pembrolizumab	Administered via intravenous (IV) infusion at a dose of 400 mg on Day 1 of every 6-week cycle for up to 9 adjuvant cycles for Adjuvant Cohort participants, or at a dose of 200 mg on Day 1 of every cycle for up to four 3-week neoadjuvant cycles and up to thirteen 3-week adjuvant cycles for Perioperative Cohort participants.
BIOLOGICAL	Intismeran autogene	Administered via intramuscular (IM) injection at a dose of 1 mg every 3 weeks for a total of up to 9 adjuvant doses for Adjuvant Cohort participants, or at a dose of 1 mg every 3 weeks for a total of up to 9 doses in the neoadjuvant and adjuvant periods for Perioperative Cohort participants.
OTHER	Placebo	Intismeran autogene diluent only (saline and/or dextrose) administered via IM injection Q3W for up to 9 doses.
BIOLOGICAL	Enfortumab Vedotin	Administered via IV infusion at a dose of 1.25 mg/kg on Day 1 and Day 8 of every cycle for up to four 3-week neoadjuvant cycles and up to five 3-week adjuvant cycles for Perioperative Cohort participants.
PROCEDURE	Surgery (RC plus PLND)	Curative intent surgery (RC plus PLND) will be administered to all participants in the Perioperative Cohort and will be done in accordance with the American Urological Association/American Society for Radiation Oncology/American Society of Clinical Oncology/Society of Urologic Oncology guidelines. RC plus PLND will be performed within 6 weeks of the last dose of neoadjuvant intismeran autogene plus pembrolizumab plus EV treatment. Adjuvant intismeran autogene plus pembrolizumab plus EV treatment will begin within 8 weeks of completing RC plus PLND.

Timeline

• Start date: 2024-03-28
• Primary completion: 2027-04-23
• Completion: 2031-10-20
• First posted: 2024-03-12
• Last updated: 2026-01-13

Locations

74 sites across 16 countries: United States, Australia, Canada, Chile, Colombia, France, Germany, Italy, New Zealand, Peru, Poland, South Korea, Spain, Sweden, Turkey (Türkiye), United Kingdom

Regulatory

• FDA-regulated drug study