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NCT Number: NCT06305767

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

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.

Active, Not Recruiting

This study is active but is not currently recruiting participants.

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Key information

Conditions

Bladder Cancer Female Urogenital Diseases Female Urogenital Diseases and Pregnancy Complications Male Urogenital Diseases Neoplasms Neoplasms by Site Parkinson Disease 4, Autosomal Dominant Lewy Body Urinary Bladder Diseases Urinary Bladder Neoplasms Urogenital Diseases Urogenital Neoplasms Urologic Diseases Urologic Neoplasms

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1 / Phase 2

Primary location

Macquarie University-MQ Health Clinical Trials Unit ( Site 1803), Macquarie University, New South Wales, Australia

Loading trial locations.

About this study

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

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

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.

Other names: MK-3475, Keytruda®

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.

Other names: V940

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.

Other names: PADCEV®

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.

Primary outcomes

  1. Adjuvant Cohort: Disease Free Survival (DFS)

    Time frame: Up to approximately 28 months

    DFS is defined as the time from randomization until death from any cause, or presence of disease per investigator assessment with muscle-invasive (≥pT2) disease or any high-grade non-muscle invasive disease in the urothelial tract (upper tract or lower tract) on imaging and biopsy, and/or disease recurrence outside the urothelial tract on imaging with or without confirmation by biopsy. DFS will be reported for the Adjuvant Cohort.

  2. Perioperative Cohort: Number of Participants Who Experience an Adverse Event (AE)

    Time frame: Up to approximately 19 months

    An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study treatment. The number of participants who experience AEs will be reported for the Perioperative Cohort.

  3. Perioperative Cohort: Number of Participants Who Discontinue Study Treatment Due to AE

    Time frame: Up to approximately 16 months

    An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study treatment. The number of participants who discontinue study treatment due to an AE will be reported for the Perioperative Cohort.

Secondary outcomes

  1. Adjuvant Cohort: Overall Survival (OS)

    Time frame: Up to approximately 28 months

    Overall survival is defined as the time from randomization to death due to any cause. OS will be reported for the Adjuvant Cohort.

  2. Adjuvant Cohort: Distant Metastasis-Free Survival (DMFS)

    Time frame: Up to approximately 28 months

    DMFS is defined as the time from randomization until death from any cause, or disease recurrence outside the urothelial tract on imaging with or without confirmation by biopsy, per investigator assessment. DMFS will be reported for the Adjuvant Cohort.

  3. Adjuvant Cohort: Number of Participants Who Experience an AE

    Time frame: Up to approximately 16 months

    An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study treatment. The number of participants who experience an AE will be reported for the Adjuvant Cohort.

  4. Adjuvant Cohort: Number of Participants Who Discontinue Study Treatment Due to an AE

    Time frame: Up to approximately 13 months

    An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study treatment. The number of participants who discontinue study treatment due to an AE will be presented for the Adjuvant Cohort.

  5. Perioperative Cohort: Pathologic Complete Response (pCR) Rate

    Time frame: Up to approximately 18 weeks

    pCR is defined as the absence of viable tumor (pT0N0) in examined tissue from RC plus PLND as assessed by the investigator. pCR rate will be reported as the percentage of participants in the Perioperative Cohort having pCR.

  6. Perioperative Cohort: Pathologic Downstaging (pDS) Rate

    Time frame: Up to approximately 18 weeks

    pDS is defined as participants with <pT2 (includes pT0, pTis, pTa, pT1) and N0 in examined tissue from RC plus PLND as assessed by the investigator. pDS rate will be reported as the percentage of participants in the Perioperative Cohort having pDS.

Sponsors and collaborators

Lead sponsor

Merck Sharp & Dohme LLC

Industry

Collaborators

  • ModernaTX, Inc.

Registry information

Official study title

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

Important dates

Study start
2024
Primary completion
2027
Study completion
2031
First posted
Mar 12, 2024
Registry last updated
Jan 13, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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