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Phase 1

Phase 2

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

Sponsor:

Merck Sharp & Dohme LLC

Code:

NCT06305767

Conditions

Bladder Cancer

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Interventions

Pembrolizumab

Intismeran autogene

Placebo

Enfortumab Vedotin

Surgery (RC plus PLND)

Study Details

Brief 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.

Conditions

Bladder Cancer

Study ID

NCT06305767

Start date

Mar 28, 2024

Status verified date

Jan, 2026

Completion date

Oct 20, 2031

Anticipated

Primary completion date

Apr 23, 2027

Anticipated

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Inclusion Criteria:

The main inclusion criteria include but are not limited to the following:

Has a histological diagnosis of urothelial carcinoma (UC)
Must provide blood samples per protocol, to enable intismeran autogene production, and circulating tumor deoxyribonucleic acid testing
Has an Eastern Cooperative Oncology Group performance status of 0 to 2 assessed within 7 days before randomization
Must provide a formalin-fixed paraffin-embedded tumor tissue sample for next generation sequencing

Adjuvant Cohort:

Has MIUC
Has high-risk pathologic disease after radical resection
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
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

Exclusion Criteria:

The main exclusion criteria include but are not limited to the following:

Has received a live or live-attenuated vaccine within 30 days before the first dose of study intervention
Has known additional malignancy that is progressing or has required active treatment ≤3 years prior to study randomization
Has current pneumonitis/interstitial lung disease
Has active infection requiring systemic therapy
Has active hepatitis B and hepatitis C virus infection

Adjuvant Cohort:

Has received prior systemic anticancer therapy
Has received prior neoadjuvant therapy, with the exception of neoadjuvant cisplatin-based chemotherapy for MIUC
Has severe hypersensitivity to either intismeran autogene or pembrolizumab (MK-3475) and/or any of their excipients

Perioperative Cohort:

Has received any prior systemic treatment, cancer vaccine treatment, chemoradiation, and/or radiation therapy treatment for MIBC
Has severe hypersensitivity to either intismeran autogene, pembrolizumab, or EV and/or any of their excipients
Has ongoing sensory or motor neuropathy
Has active keratitis or corneal ulcerations

Study Design

Enrollment

230 participants

Anticipated

Allocation

Randomized

Intervention Model

Parallel Assignment

Primary purpose

Treatment

Interventions and Outcome Measures

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.

Interventions

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.

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.

Placebo

Intismeran autogene diluent only (saline and/or dextrose) administered via IM injection Q3W for up to 9 doses.

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.

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.

Primary outcome measure

Adjuvant Cohort: Disease Free Survival (DFS) [ Time Frame: Up to approximately 28 months ]
Perioperative Cohort: Number of Participants Who Experience an Adverse Event (AE) [ Time Frame: Up to approximately 19 months ]
Perioperative Cohort: Number of Participants Who Discontinue Study Treatment Due to AE [ Time Frame: Up to approximately 16 months ]

Central Contacts and Locations

Central contacts

Toll Free Number

1-888-577-8839 Trialsites@msd.com

Locations

UCLA Hematology/Oncology - Westwood (Building 200 Suite 140)-Department of Urology/Institute of Uro ( Site 0104)

Recruiting

Los Angeles, California, United States, 90095

Contacts

Study Coordinator

888-577-8839

AdventHealth Orlando-AdventHealth Medical Group Hematology & Oncology at Orlandoc ( Site 0102)

Recruiting

Orlando, Florida, United States, 32804

Contacts

Study Coordinator

407-303-5600

University of Chicago Medical Center ( Site 0109)

Recruiting

Chicago, Illinois, United States, 60637

Contacts

Study Coordinator

888-577-8839

Icahn School of Medicine at Mount Sinai ( Site 0101)

Recruiting

New York, New York, United States, 10029

Contacts

Study Coordinator

888-577-8839

Duke Cancer Institute ( Site 0107)

Recruiting

Durham, North Carolina, United States, 27710

Contacts

Study Coordinator

888-577-8839

Fox Chase Cancer Center ( Site 0106)

Recruiting

Philadelphia, Pennsylvania, United States, 19111

Contacts

Study Coordinator

888-577-8839

Princess Margaret Cancer Centre ( Site 0003)

Recruiting

Toronto, Ontario, Canada, M5G 2M9

Contacts

Study Coordinator

416-946-2246

Centre Hospitalier de l'Université de Montréal ( Site 0005)

Recruiting

Montreal, Quebec, Canada, H2X 3E4

Contacts

Study Coordinator

514-890-8000

Centre intégré de cancérologie du CHU de Québec Université Laval, Hôpital de l'Enfant-Jésus ( Site 0001)

Recruiting

Québec, Quebec, Canada, G1J 1Z4

Contacts

Study Coordinator

418-525-4444 x67512

Centre intégré universitaire de santé et de services sociaux de l'Estrie - Centre Hospitalier Univer ( Site 0002)

Recruiting

Sherbrooke, Quebec, Canada, J1H 5H4

Contacts

Study Coordinator

819-346-1110x13446

More Information

Sponsor

Merck Sharp & Dohme LLC

Last update posted

Jan 6, 2026

Last verified

Jan, 2026

Keywords

Programmed Cell Death-1 (PD1, PD-1)
Programmed Cell Death 1 Ligand 1 (PDL1, PD-L1)
Programmed Cell Death 1 Ligand 2 (PDL2, PD-L2)

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-16. This information was provided to ClinicalTrials.gov by Merck Sharp & Dohme LLC on 2026-01-06.