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

PHASE1PHASE2ACTIVE_NOT_RECRUITING

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.

Study details:

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

Eligibility criteria

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

Inclusion criteria

  1. Has a histological diagnosis of urothelial carcinoma (UC)
  2. Must provide blood samples per protocol, to enable intismeran autogene production, and circulating tumor deoxyribonucleic acid testing
  3. Has an Eastern Cooperative Oncology Group performance status of 0 to 2 assessed within 7 days before randomization
  4. Must provide a formalin-fixed paraffin-embedded tumor tissue sample for next generation sequencing
  5. Has MIUC
  6. Has high-risk pathologic disease after radical resection
  7. For participants who have not received cisplatin-based neoadjuvant chemotherapy, are ineligible to receive cisplatin according to protocol pre-defined criteria
  8. Has MIBC
  9. Is deemed eligible for RC and PLND and agrees to undergo curative intent standard RC and PLND and neoadjuvant and adjuvant treatment per protocol
  10. Is ineligible to receive cisplatin according to protocol pre-defined criteria

Exclusion criteria

  1. Has received a live or live-attenuated vaccine within 30 days before the first dose of study intervention
  2. Has known additional malignancy that is progressing or has required active treatment ≤3 years prior to study randomization
  3. Has current pneumonitis/interstitial lung disease
  4. Has active infection requiring systemic therapy
  5. Has active hepatitis B and hepatitis C virus infection
  6. Has received prior systemic anticancer therapy
  7. Has received prior neoadjuvant therapy, with the exception of neoadjuvant cisplatin-based chemotherapy for MIUC
  8. Has severe hypersensitivity to either intismeran autogene or pembrolizumab (MK-3475) and/or any of their excipients
  9. Has received any prior systemic treatment, cancer vaccine treatment, chemoradiation, and/or radiation therapy treatment for MIBC
  10. Has severe hypersensitivity to either intismeran autogene, pembrolizumab, or EV and/or any of their excipients
  11. Has ongoing sensory or motor neuropathy
  12. Has active keratitis or corneal ulcerations

Eligibility

Age eligible for study : NA

Healthy volunteers accepted : No

Gender eligible for study: ALL

Things to know

Study dates

Study start:

Primary completion:

Study completion finish:

study type

Study type

TREATMENT

phase

Phase

    PHASE1PHASE2

trial

Study ID

NCT06305767

Intervention or treatment

BIOLOGICAL: Pembrolizumab

BIOLOGICAL: Intismeran autogene

OTHER: Placebo

BIOLOGICAL: Enfortumab Vedotin

PROCEDURE: Surgery (RC plus PLND)

Conditions

  • Bladder Cancer

  • Condition: Bladder Cancer

  • BIOLOGICAL: Pembrolizumab and other drugs

  • Macquarie University, New South Wales, Australia and more

  • Sponsor: Merck Sharp & Dohme LLC

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Are you running this trial?

If you're a clinic or sponsor, you can claim this study

Research sites nearby

Closest Location:

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

Select from list below to view details:

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

    Macquarie University, New South Wales, Australia

  • Westmead Hospital ( Site 1802)

    Westmead, New South Wales, Australia

  • Mater Misericordiae Limited ( Site 1808)

    South Brisbane, Queensland, Australia

  • One Clinical Research ( Site 1807)

    Nedlands, Western Australia, Australia

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Who is running the clinical trial?

MS&DL

Merck Sharp & Dohme LLC

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 + 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.
Biological: Pembrolizumab, Biological: Intismeran autogene
    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.
    Biological: Pembrolizumab, Other: Placebo
      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.
      Biological: Pembrolizumab, Biological: Intismeran autogene, Biological: Enfortumab Vedotin, Procedure: Surgery (RC plus PLND)

        What is the study measuring?

        Primary Outcome

        MeasureDescriptionTime 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

        MeasureDescriptionTime 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
        Are you running this trial?If you're a clinic or sponsor, you can claim this study.
        Claim this trial

        References

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

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