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

PHASE1PHASE2RECRUITING

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 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.

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Study details:

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

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Eligibility criteria

Researchers look for people who fit a certain description, called eligibility criteria. See if you qualify.

Inclusion criteria

  • Must provide blood samples per protocol, to enable V940 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
  • Has MIUC
  • Has dominant histology of urothelial carcinoma (UC)
  • 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
  • Has MIBC
  • Has a histological diagnosis 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
  • Exclusion criteria

  • 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
  • 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 V940 or pembrolizumab (MK-3475) and/or any of their excipients
  • Has received any prior systemic treatment, cancer vaccine treatment, chemoradiation, and/or radiation therapy treatment for MIBC
  • Has severe hypersensitivity to either V940, pembrolizumab, or EV and/or any of their excipients
  • Has ongoing sensory or motor neuropathy
  • Has active keratitis or corneal ulcerations
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    Eligibility

    Age eligible for study : 18 and older

    Healthy volunteers accepted : No

    Gender eligible for study: All

    Things to know

    Study dates

    Study start: 2024-03-28

    Primary completion: 2026-10-08

    Study completion finish: 2031-04-08

    study type

    Study type

    TREATMENT

    phase

    Phase

      PHASE1

      PHASE2

    trial

    Trial ID

    NCT06305767

    Intervention or treatment

    BIOLOGICAL: Pembrolizumab

    BIOLOGICAL: V940

    OTHER: Placebo

    BIOLOGICAL: Enfortumab Vedotin

    PROCEDURE: Surgery (RC plus PLND)

    Conditions

    • Bladder Cancer

    Find a site

    Closest Location:

    Macquarie University-MQ Health Clinical Trials Unit ( Site 1803)

    Research sites nearby

    Select from list below to view details:

    • Macquarie University-MQ Health Clinical Trials Unit ( Site 1803)

      Macquarie University, New South Wales, Australia

    • Westmead Hospital-Department of Medical Oncology ( Site 1802)

      Westmead, New South Wales, Australia

    • One Clinical Research ( Site 1807)

      Nedlands, Western Australia, Australia

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    Study Plan

    This section provides details of the study plan, including how the study is designed and what the study is measuring.

    How is the study designed?

    Participant Group/ArmIntervention/Treatment
    EXPERIMENTAL: Adjuvant Cohort: Pembrolizumab + V940
    • Adjuvant Cohort participants receive 400 mg of pembrolizumab via intravenous (IV) infusion on Day 1 of every 6-week cycle for up to 9 cycles, plus 1 mg of V940 via intramuscular (IM) injection every 3 weeks up to a total of 9 doses. V940 doses may begin as soon as Day 22 of Cycle 1. The total duration of treatment is up to approximately 13 months.
    BIOLOGICAL: Pembrolizumab
    • Administered via 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 3-week cycle for up to 4 neoadjuvant cycles, and up to 13 adjuvant cycles for Perioperative Cohort participants.
    ACTIVE_COMPARATOR: Adjuvant Cohort: Pembrolizumab + Placebo
    • Adjuvant Cohort participants receive pembrolizumab 400 mg via IV infusion on Day 1 of each 6-week cycle for up to 9 cycles. Placebo will be administered every 3 weeks up to a total of 9 doses. The total duration of treatment is up to approximately 13 months.
    BIOLOGICAL: Pembrolizumab
    • Administered via 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 3-week cycle for up to 4 neoadjuvant cycles, and up to 13 adjuvant cycles for Perioperative Cohort participants.
    EXPERIMENTAL: Perioperative Cohort: Pembrolizumab + V940 + Enfortumab Vedotin (EV) and Surgery
    • Curative intent surgery (radical cystectomy \[RC\] plus pelvic lymph node dissection \[PLND\]) will be administered to all participants in the Perioperative Cohort. RC plus PLND will be performed approximately 15 weeks after allocation to the Perioperative Cohort and within 6 weeks of the last dose of neoadjuvant V940 plus pembrolizumab plus EV treatment. Adjuvant V940 plus pembrolizumab plus EV treatment will begin within 8 weeks of completing RC plus PLND. Pembrolizumab will be administered via IV infusion at a dose of 200 mg on Day 1 of every 3-week cycle for up to 4 neoadjuvant cycles and up to 13 adjuvant cycles. V940 will be administered at a dose of 1 mg every 3 weeks for a total of up to 9 doses in the neoadjuvant and adjuvant periods. EV will be administered via IV infusion at a dose of 1.25 mg/kg on Day 1 and Day 8 of every 3-week cycle for up to 4 neoadjuvant cycles and up to 5 adjuvant cycles. The total duration of treatment is up to approximately 16 months.
    BIOLOGICAL: Pembrolizumab
    • Administered via 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 3-week cycle for up to 4 neoadjuvant cycles, and up to 13 adjuvant cycles for Perioperative Cohort participants.

    What is the study measuring?

    Primary outcome

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

    Secondary outcome

    Secondary Outcome MeasureSecondary Outcome DescriptionSecondary Outcome Time Frame
    Adjuvant Cohort: Overall Survival (OS)Overall survival is defined as the time from randomization to death due to any cause. OS will be reported for the Adjuvant Cohort.Up to approximately 28 months
    Adjuvant Cohort: Distant Metastasis-Free Survival (DMFS)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.Up to approximately 28 months
    Adjuvant Cohort: Number of Participants Who Experience an AEAn 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.Up to approximately 16 months
    Adjuvant Cohort: Number of Participants Who Discontinue Study Treatment Due to an AEAn 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.Up to approximately 13 months
    Perioperative Cohort: Pathologic Complete Response (pCR) RatepCR 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.Up to approximately 18 weeks
    Perioperative Cohort: Pathologic Downstaging (pDS) RatepDS 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.Up to approximately 18 weeks

    Frequently Asked Questions

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    References

    Clinical Trials Gov: A Clinical Study of V940 Treatment and Pembrolizumab in People With Bladder Cancer (V940-005/INTerpath-005)

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