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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

TREATMENT

Phase

PHASE1

PHASE2

Trial ID

NCT06305767

Intervention or treatment

BIOLOGICAL: Pembrolizumab

BIOLOGICAL: V940

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

You may be eligible to participate in this trial based on your search. Check eligibility by answering some questions.

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

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

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/Arm	Intervention/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 Measure	Primary Outcome Description	Primary 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 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 discontinue study treatment due to an AE will be reported for the Perioperative Cohort.	Up to approximately 16 months

Secondary outcome

Secondary Outcome Measure	Secondary Outcome Description	Secondary 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 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 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 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 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) Rate	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.	Up to approximately 18 weeks
Perioperative Cohort: Pathologic Downstaging (pDS) Rate	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.	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)