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

Phase 2Active Not RecruitingNCT06305767

Merck Sharp & Dohme LLC230 enrolled

Overview

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.

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

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

DOUBLE

Enrollment

230

Conditions

Interventions

PembrolizumabBIOLOGICAL

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 autogeneBIOLOGICAL

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.

PlaceboOTHER

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

Enfortumab VedotinBIOLOGICAL

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)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.

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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

Outcomes

Primary Outcomes

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.

Time frame: 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.

Time frame: 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.

Time frame: Up to approximately 16 months

Secondary Outcomes

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.

Time frame: 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.

Time frame: Up to approximately 28 months

Adjuvant Cohort: Number of Participants Who Experience an AE

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: Up to approximately 18 weeks

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

Overview

Conditions

Interventions

Eligibility

Locations (74)

Outcomes

Primary Outcomes

Secondary Outcomes