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

Conditions

• Bladder Cancer

Eligibility Criteria

Sex

ALL

Age

18 Years - N/A

Healthy Volunteers

Not accepted

Interventions

• Pembrolizumab — BIOLOGICAL
  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.
• Intismeran autogene — BIOLOGICAL
  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.
• Placebo — OTHER
  Intismeran autogene diluent only (saline and/or dextrose) administered via IM injection Q3W for up to 9 doses.
• Enfortumab Vedotin — BIOLOGICAL
  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.
• Surgery (RC plus PLND) — PROCEDURE
  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.

Study Details

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.

Key Dates

Start date

Mar 28, 2024

Status verified

Jan 2026

Primary completion

Apr 23, 2027

Completion

Oct 20, 2031

Study Design

Enrollment

230 participants (estimated)

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Arms

• Experimental: Adjuvant Cohort: Pembrolizumab + Intismeran autogene
  Adjuvant Cohort participants receive adjuvant treatment with up to 9 cycles of pembrolizumab plus up to a total of 9 doses of intismeran autogene. Intismeran autogene doses may begin as soon as Day 22 of Cycle 1. The total duration of treatment is up to approximately 13 months.
• Active Comparator: Adjuvant Cohort: Pembrolizumab + Placebo
  Adjuvant Cohort participants receive adjuvant treatment with up to 9 cycles of pembrolizumab plus up to a total of 9 doses of placebo. Placebo doses may begin as soon as Day 22 of Cycle 1. The total duration of treatment is up to approximately 13 months.
• Experimental: Perioperative Cohort: Pembrolizumab + Intismeran autogene + EV and Surgery
  Participants will receive neoadjuvant treatment with up to 4 cycles of pembrolizumab plus EV and 1 to 4 doses of intismeran autogene, followed by radical cystectomy \[RC\] plus pelvic lymph node dissection \[PLND\], and then adjuvant treatment with up to 13 cycles of pembrolizumab plus up to 5 cycles of EV and 5 to 8 doses of intismeran autogene (for a total of 9 neoadjuvant plus adjuvant Intismeran autogene doses), or until any of the protocol-specified criteria for discontinuation of study intervention are met. The total duration of treatment is up to approximately 16 months.

Primary Outcome Measure

Adjuvant Cohort: Disease Free Survival (DFS) [ Time Frame: Up to approximately 28 months ]

Locations (10)

Find similar trials in Los Angeles, CA

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