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:
- 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 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
Perioperative Cohort:
- 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
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 (72)
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
Icahn School of Medicine at Mount Sinai ( Site 0101)
🇺🇸New York, New York, United States
University of Chicago Medical Center ( Site 0109)
🇺🇸Chicago, Illinois, United States
University of Iowa ( Site 0110)
🇺🇸Iowa City, Iowa, 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
Macquarie University-MQ Health Clinical Trials Unit ( Site 1803)
🇦🇺Macquarie University, New South Wales, Australia
Westmead Hospital ( Site 1802)
🇦🇺Westmead, New South Wales, Australia
One Clinical Research ( Site 1807)
🇦🇺Nedlands, Western Australia, Australia
BC Cancer Vancouver ( Site 0004)
🇨🇦Vancouver, British Columbia, Canada
Princess Margaret Cancer Centre ( Site 0003)
🇨🇦Toronto, Ontario, Canada
Centre Hospitalier de l'Université de Montréal ( Site 0005)
🇨🇦Montréal, Quebec, Canada
Centre intégré de cancérologie du CHU de Québec Université Laval, Hôpital de l'Enfant-Jésus ( Site 0001)
🇨🇦Quebec City, Quebec, Canada
Centre intégré universitaire de santé et de services sociaux de l'Estrie - Centre Hospitalier Univer ( Site 0002)
🇨🇦Sherbrooke, Quebec, Canada
Bradfordhill-Clinical Area ( Site 1501)
🇨🇱Recoleta, Santiago, Region M. De Santiago, Chile
FALP ( Site 1500)
🇨🇱Santiago, Region M. De Santiago, Chile
Pontificia Universidad Catolica de Chile-Centro del Cáncer ( Site 1503)
🇨🇱Santiago, Region M. De Santiago, Chile
ONCOCENTRO APYS-ACEREY ( Site 1506)
🇨🇱Viña del Mar, Valparaiso, Chile
Sociedad De Oncologia Y Hematologia Del Cesar-Oncology ( Site 1605)
🇨🇴Valledupar, Cesar, Colombia
Instituto Nacional De Cancerologia-Oncología Clínica ( Site 1606)
🇨🇴Bogota, Cundinamarca, Colombia
Clínica Universitaria Colombia ( Site 1600)
🇨🇴Bogotá, Distrito Capital De Bogota, Colombia
Fundacion Valle del Lili- CIC-Oncology CIC ( Site 1608)
🇨🇴Cali, Valle Del Cauca, Colombia
Oncopole Claudius Regaud ( Site 0302)
🇫🇷Toulouse, Haute-Garonne, France
Gustave Roussy ( Site 0303)
🇫🇷Villejuif, Ile-de-France, France
Institut de Cancérologie de l'Ouest ( Site 0300)
🇫🇷ANGERS cedex 02, Maine-et-Loire, France
Hopital Claude Huriez - CHU de Lille ( Site 0301)
🇫🇷Lille, Nord, France
Hôpital Saint-Louis ( Site 0304)
🇫🇷Paris, France
klinikum rechts der isar der technischen universität münchen-Urologische Klinik und Poliklinik ( Site 0401)
🇩🇪Munich, Bayern, Germany
Caritas-Krankenhaus St. Josef-Klinik fuer Urologie ( Site 0404)
🇩🇪Regensburg, Bayern, Germany
Universitätsklinikum Halle-Universitätsklinik und Poliklinik für Urologie ( Site 0402)
🇩🇪Halle, Sachsen-Anhalt, Germany
Universitaetsklinikum Carl Gustav Carus Dresden-Klinik und Poliklinik für Urologie ( Site 0405)
🇩🇪Dresden, Sachsen, Germany
Charité Universitaetsmedizin Berlin - Campus Mitte ( Site 0400)
🇩🇪Berlin, Germany
Fondazione Policlinico Universitario Agostino Gemelli IRCCS -Medical Oncology ( Site 0504)
🇮🇹Roma, Lazio, Italy
Ospedale San Martino-U.O. Oncologia Medica 1 ( Site 0500)
🇮🇹Genova, Liguria, Italy
Fondazione IRCCS Istituto Nazionale dei Tumori-Struttura Complessa Oncologia Medica 1 ( Site 0502)
🇮🇹Milan, Lombardia, Italy
Azienda Ospedaliera Di Rilievo Nazionale A. Cardarelli-UOSC Oncologia ( Site 0503)
🇮🇹Naples, Napoli, Italy
Ospedale San Raffaele-Oncologia Medica ( Site 0501)
🇮🇹Milano, Italy
Korea University Anam Hospital ( Site 2002)
🇰🇷Seoul, Korea, Republic of
Seoul National University Hospital-Urology ( Site 2000)
🇰🇷Seoul, Korea, Republic of
Samsung Medical Center-Urology ( Site 2001)
🇰🇷Seoul, Korea, Republic of
Auckland City Hospital ( Site 1901)
🇳🇿Auckland, New Zealand
IPOR Instituto Peruano de Oncología & Radioterapia ( Site 1702)
🇵🇪Lima, Peru
Oncosalud ( Site 1701)
🇵🇪Lima, Peru
Hospital Militar Central Luis Arias Schereiber ( Site 1700)
🇵🇪Lima, Peru
Centrum Onkologii im. Prof. Franciszka Lukaszczyka-Ambulatorium Chemioterapii ( Site 0801)
🇵🇱Bydgoszcz, Kujawsko-pomorskie, Poland
Narodowy Instytut Onkologii im. Marii Sklodowskiej-Curie - P-Klinika Nowotworów Układu Moczowego ( Site 0800)
🇵🇱Warszawa, Mazowieckie, Poland
Swietokrzyskie Centrum Onkologii, Samodzielny Publiczny Zaklad Opieki Zdrowotnej ( Site 0806)
🇵🇱Kielce, Swietokrzyskie, Poland
Clinical Research Center Spółka z ograniczoną odpowiedzialnością MEDIC-R Sp.k ( Site 0805)
🇵🇱Poznan, Wielkopolskie, Poland
Szpital Wojewódzki im. Mikoaja Kopernika w Koszalinie-Oddzial Dzienny Chemioterapii ( Site 0802)
🇵🇱Koszalin, Zachodniopomorskie, Poland
Hospital Germans Trias i Pujol-Instituto Catalán de Oncología de Badalona ( Site 1006)
🇪🇸Badalona, Barcelona, Spain
Hospital Universitario Ramón y Cajal-Medical Oncology ( Site 1005)
🇪🇸Madrid, Madrid, Comunidad De, Spain
HOSPITAL UNIVERSITARIO QUIRONSALUD MADRID-ONCOLOGIA MEDICA ( Site 1003)
🇪🇸Pozuelo de Alarcon, Madrid, Spain
Hospital Universitari Vall d'Hebron-Oncology ( Site 1002)
🇪🇸Barcelona, Spain
HOSPITAL UNIVERSITARIO VIRGEN DEL ROCIO-Medical Oncology ( Site 1001)
🇪🇸Sevilla, Spain
Karolinska Universitetssjukhuset Solna ( Site 1101)
🇸🇪Stockholm, Stockholms Lan, Sweden
Akademiska sjukhuset-Blod- och tumörsjukdomar ( Site 1102)
🇸🇪Uppsala, Uppsala Lan, Sweden
Hacettepe Universite Hastaneleri-oncology hospital ( Site 1200)
🇹🇷Ankara, Turkey
Memorial Ankara Hastanesi-Medical Oncology ( Site 1204)
🇹🇷Ankara, Turkey
Ankara Bilkent Şehir Hastanesi-Medical Oncology ( Site 1201)
🇹🇷Ankara, Turkey
Koc Universitesi Hastanesi ( Site 1206)
🇹🇷Istanbul, Turkey
T.C. Saglik Bakanligi Turkiye Kamu Hastaneleri Kurumu - Baki-Istanbul Bakirkoy Sadi Konuk Training ( Site 1205)
🇹🇷Istanbul, Turkey
TC Saglik Bakanligi Goztepe Prof. Dr. Suleyman Yalcin Sehir Hastanesi-oncology ( Site 1202)
🇹🇷Istanbul, Turkey
Ege Universitesi Hastanesi-Medical Oncology ( Site 1203)
🇹🇷Izmir, Turkey
Torbay Hospital ( Site 1303)
🇬🇧Torquay, Devon, United Kingdom
Royal Free Hospital ( Site 1300)
🇬🇧London, England, United Kingdom
Gartnavel General Hospital-Clinical Trials Unit ( Site 1301)
🇬🇧Glasgow, Glasgow City, United Kingdom
St Bartholomew's Hospital-Centre for Experimental Cancer Medicine ( Site 1302)
🇬🇧London, London, City Of, United Kingdom
The Christie NHS Foundation Trust ( Site 1306)
🇬🇧Manchester, United Kingdom