A Clinical Study of Intismeran Autogene (V940) Treatment and Pembrolizumab in People With Bladder Cancer (V940-005/INTerpath-005)
- Conditions
- Bladder Cancer
- Interventions
- Other: PlaceboBiological: Enfortumab VedotinProcedure: Surgery (RC plus PLND)
- Registration Number
- NCT06305767
- Lead Sponsor
- Merck Sharp & Dohme LLC
- Brief Summary
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.
- Detailed Description
Enrollment of participants into the Phase 1 Perioperative Cohort of this study is planned to start in approximately April of 2025.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 230
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
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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Perioperative Cohort: Pembrolizumab + Intismeran autogene + EV and Surgery Intismeran autogene 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. Perioperative Cohort: Pembrolizumab + Intismeran autogene + EV and Surgery Enfortumab Vedotin 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. Adjuvant Cohort: Pembrolizumab + Intismeran autogene Pembrolizumab 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. Adjuvant Cohort: Pembrolizumab + Intismeran autogene 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. Adjuvant Cohort: Pembrolizumab + Placebo Pembrolizumab 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. Adjuvant Cohort: Pembrolizumab + Placebo 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. Perioperative Cohort: Pembrolizumab + Intismeran autogene + EV and Surgery Pembrolizumab 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. Perioperative Cohort: Pembrolizumab + Intismeran autogene + EV and Surgery Surgery (RC plus PLND) 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.
- Primary Outcome Measures
Name Time Method Adjuvant Cohort: Disease Free Survival (DFS) 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.
Perioperative Cohort: Number of Participants Who Experience an Adverse Event (AE) 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.
Perioperative Cohort: Number of Participants Who Discontinue Study Treatment Due to AE 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 Outcome Measures
Name Time Method Adjuvant Cohort: Overall Survival (OS) 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.
Adjuvant Cohort: Distant Metastasis-Free Survival (DMFS) 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.
Adjuvant Cohort: Number of Participants Who Experience an AE 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.
Adjuvant Cohort: Number of Participants Who Discontinue Study Treatment Due to an AE 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.
Perioperative Cohort: Pathologic Complete Response (pCR) Rate 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.
Perioperative Cohort: Pathologic Downstaging (pDS) Rate 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.
Trial Locations
- Locations (74)
UCLA Hematology/Oncology - Westwood (Building 200 Suite 140)-Department of Urology/Institute of Uro ( Site 0104)
🇺🇸Los Angeles, California, United States
AdventHealth Orlando-AdventHealth Medical Group Hematology & Oncology at Orlandoc ( Site 0102)
🇺🇸Orlando, Florida, United States
University of Chicago Medical Center ( Site 0109)
🇺🇸Chicago, Illinois, United States
University of Iowa ( Site 0110)
🇺🇸Iowa City, Iowa, United States
Icahn School of Medicine at Mount Sinai ( Site 0101)
🇺🇸New York, New York, United States
Duke Cancer Institute ( Site 0107)
🇺🇸Durham, North Carolina, United States
Cleveland Clinic Main ( Site 0100)
🇺🇸Cleveland, Ohio, United States
Fox Chase Cancer Center ( Site 0106)
🇺🇸Philadelphia, Pennsylvania, United States
UT Southwestern Medical Center ( Site 0103)
🇺🇸Dallas, Texas, United States
Houston Methodist Hospital-Department of Urology ( Site 0111)
🇺🇸Houston, Texas, United States
Scroll for more (64 remaining)UCLA Hematology/Oncology - Westwood (Building 200 Suite 140)-Department of Urology/Institute of Uro ( Site 0104)🇺🇸Los Angeles, California, United StatesStudy CoordinatorContact888-577-8839