Bladder CancerPhase 1/2NCT06305767
A Clinical Study of Intismeran Autogene (V940) Treatment and Pembrolizumab in People With Bladder Cancer (V940-005/INTerpath-005)
A Phase 1/2 study testing Pembrolizumab, Intismeran autogene and Enfortumab Vedotin in people with Bladder Cancer, run by Merck Sharp & Dohme LLC at 74 sites in 16 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Bladder Cancer
- What is being tested?
- Pembrolizumab, Intismeran autogene and Enfortumab Vedotin
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 230 participants
- Where
- 74 sitesin 16 countries
- Study dates
- 28 Mar 2024to 20 Oct 2031
- Phase
- Phase 1/2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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:
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- 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
Who cannot join
- 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
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- 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
Trial locations and contacts
74 sites in 16 countries.
74 sites in 16 countries
United States10 sites
University of Chicago Medical Center ( Site 0109)
Chicago, Illinois, 60637
Cleveland Clinic Main ( Site 0100)
Cleveland, Ohio, 44195
UT Southwestern Medical Center ( Site 0103)
Dallas, Texas, 75390
Duke Cancer Institute ( Site 0107)
Durham, North Carolina, 27710
Houston Methodist Hospital-Department of Urology ( Site 0111)
Houston, Texas, 77030
University of Iowa ( Site 0110)
Iowa City, Iowa, 52242
UCLA Hematology/Oncology - Westwood (Building 200 Suite 140)-Department of Urology/Institute of Uro ( Site 0104)
Los Angeles, California, 90095
Icahn School of Medicine at Mount Sinai ( Site 0101)
New York, New York, 10029
AdventHealth Orlando-AdventHealth Medical Group Hematology & Oncology at Orlandoc ( Site 0102)
Orlando, Florida, 32804
Fox Chase Cancer Center ( Site 0106)
Philadelphia, Pennsylvania, 19111
Turkey (Türkiye)7 sites
Hacettepe Universite Hastaneleri-oncology hospital ( Site 1200)
Ankara, 06230
Memorial Ankara Hastanesi-Medical Oncology ( Site 1204)
Ankara, 06520
Ankara Bilkent Şehir Hastanesi-Medical Oncology ( Site 1201)
Ankara, 06800
Koc Universitesi Hastanesi ( Site 1206)
Istanbul, 34025
T.C. Saglik Bakanligi Turkiye Kamu Hastaneleri Kurumu - Baki-Istanbul Bakirkoy Sadi Konuk Training ( Site 1205)
Istanbul, 34147
TC Saglik Bakanligi Goztepe Prof. Dr. Suleyman Yalcin Sehir Hastanesi-oncology ( Site 1202)
Istanbul, 34722
Ege Universitesi Hastanesi-Medical Oncology ( Site 1203)
Izmir, 35100
Canada5 sites
Centre Hospitalier de l'Université de Montréal ( Site 0005)
Montreal, Quebec, H2X 3E4
Centre intégré de cancérologie du CHU de Québec Université Laval, Hôpital de l'Enfant-Jésus ( Site 0001)
Québec, Quebec, G1J 1Z4
Centre intégré universitaire de santé et de services sociaux de l'Estrie - Centre Hospitalier Univer ( Site 0002)
Sherbrooke, Quebec, J1H 5H4
Princess Margaret Cancer Centre ( Site 0003)
Toronto, Ontario, M5G 2M9
BC Cancer Vancouver ( Site 0004)
Vancouver, British Columbia, V5Z 4E6
Chile5 sites
Bradfordhill-Clinical Area ( Site 1501)
Recoleta, Santiago, Region M. de Santiago, 8420383
FALP ( Site 1500)
Santiago, Region M. de Santiago, 7500921
Pontificia Universidad Catolica de Chile ( Site 1503)
Santiago, Region M. de Santiago, 832000
CIDO SpA ( Site 1509)
Temuco, Araucania, 4810148
ONCOCENTRO APYS-ACEREY ( Site 1506)
Viña del Mar, Valparaiso, 2520598
France5 sites
Institut de Cancérologie de l'Ouest ( Site 0300)
Angers, Maine-et-Loire, 49055
Hopital Claude Huriez - CHU de Lille ( Site 0301)
Lille, Nord, 59037
Hôpital Saint-Louis ( Site 0304)
Paris, 75475
Oncopole Claudius Regaud ( Site 0302)
Toulouse, Haute-Garonne, 31059
Gustave Roussy ( Site 0303)
Villejuif, Île-de-France Region, 94805
Germany5 sites
Charité Universitaetsmedizin Berlin - Campus Mitte ( Site 0400)
Berlin, 10117
Universitaetsklinikum Carl Gustav Carus Dresden-Klinik und Poliklinik für Urologie ( Site 0405)
Dresden, Saxony, 01307
Universitätsklinikum Halle-Universitätsklinik und Poliklinik für Urologie ( Site 0402)
Halle, Saxony-Anhalt, 06120
klinikum rechts der isar der technischen universität münchen-Urologische Klinik und Poliklinik ( Site 0401)
Munich, Bavaria, 81675
Caritas-Krankenhaus St. Josef-Klinik fuer Urologie ( Site 0404)
Regensburg, Bavaria, 93053
Italy5 sites
Ospedale San Martino-U.O. Oncologia Medica 1 ( Site 0500)
Genoa, Liguria, 16132
Fondazione IRCCS Istituto Nazionale dei Tumori-Struttura Complessa Oncologia Medica 1 ( Site 0502)
Milan, Lombardy, 20133
Ospedale San Raffaele-Oncologia Medica ( Site 0501)
Milan, 20132
Azienda Ospedaliera Di Rilievo Nazionale A. Cardarelli-UOSC Oncologia ( Site 0503)
Naples, Napoli, 80131
Fondazione Policlinico Universitario Agostino Gemelli IRCCS -Medical Oncology ( Site 0504)
Rome, Lazio, 00168
Poland5 sites
Centrum Onkologii im. Prof. Franciszka Lukaszczyka-Ambulatorium Chemioterapii ( Site 0801)
Bydgoszcz, Kuyavian-Pomeranian Voivodeship, 85-796
Swietokrzyskie Centrum Onkologii, Samodzielny Publiczny Zaklad Opieki Zdrowotnej ( Site 0806)
Kielce, Świętokrzyskie Voivodeship, SWK 25-734
Oddzial Onkologii Klinicznej z Pododdzialem Chemioterapii Jednodniowej ( Site 0802)
Koszalin, West Pomeranian Voivodeship, 75-581
Clinical Research Center Spółka z ograniczoną odpowiedzialnością MEDIC-R Sp.k ( Site 0805)
Poznan, Greater Poland Voivodeship, WLK 61-731
Narodowy Instytut Onkologii im. Marii Sklodowskiej-Curie - P-Klinika Nowotworów Układu Moczowego ( Site 0800)
Warsaw, Masovian Voivodeship, 02-781
Spain5 sites
Hospital Germans Trias i Pujol-Instituto Catalán de Oncología de Badalona ( Site 1006)
Badalona, Barcelona, 08916
Hospital Universitari Vall d'Hebron-Oncology ( Site 1002)
Barcelona, 08035
Hospital Universitario Ramón y Cajal-Medical Oncology ( Site 1005)
Madrid, Madrid, Comunidad de, 28034
HOSPITAL UNIVERSITARIO QUIRONSALUD MADRID-ONCOLOGIA MEDICA ( Site 1003)
Pozuelo de Alarcón, Madrid, 28223
HOSPITAL UNIVERSITARIO VIRGEN DEL ROCIO-Medical Oncology ( Site 1001)
Seville, 41013
United Kingdom5 sites
Gartnavel General Hospital-Clinical Trials Unit ( Site 1301)
Glasgow, Glasgow City, G12 0YN
Royal Free Hospital ( Site 1300)
London, England, NW3 2QG
St Bartholomew's Hospital-Centre for Experimental Cancer Medicine ( Site 1302)
London, London, City of, EC1A 7BE
The Christie NHS Foundation Trust ( Site 1306)
Manchester, M20 4BX
Torbay Hospital ( Site 1303)
Torquay, Devon, TQ2 7AA
Australia4 sites
Macquarie University-MQ Health Clinical Trials Unit ( Site 1803)
Macquarie University, New South Wales, 2109
One Clinical Research ( Site 1807)
Nedlands, Western Australia, 6009
Mater Misericordiae Limited ( Site 1808)
South Brisbane, Queensland, 4101
Westmead Hospital ( Site 1802)
Westmead, New South Wales, 2145
Colombia4 sites
Instituto Nacional De Cancerologia-Oncología Clínica ( Site 1606)
Bogota, Cundinamarca, 111151
Clínica Universitaria Colombia ( Site 1600)
Bogotá, Bogota D.C., 111321
Fundacion Valle del Lili- CIC-Oncology CIC ( Site 1608)
Cali, Valle del Cauca Department, 760032
Sociedad De Oncologia Y Hematologia Del Cesar-Oncology ( Site 1605)
Valledupar, Cesar Department, 200001
Peru3 sites
IPOR Instituto Peruano de Oncología & Radioterapia ( Site 1702)
Lima, 15036
Oncosalud ( Site 1701)
Lima, 15036
Hospital Militar Central Luis Arias Schereiber ( Site 1700)
Lima, 1507
South Korea3 sites
Korea University Anam Hospital ( Site 2002)
Seoul, 02841
Seoul National University Hospital-Urology ( Site 2000)
Seoul, 03080
Samsung Medical Center-Urology ( Site 2001)
Seoul, 06351
Sweden2 sites
Karolinska Universitetssjukhuset Solna ( Site 1101)
Stockholm, Stockholm County, 171 64
Akademiska sjukhuset-Blod- och tumörsjukdomar ( Site 1102)
Uppsala, Uppsala County, 751 85
About this study
Official title: A Phase 1/2 Study of V940 Plus Pembrolizumab With or Without Enfortumab Vedotin in Muscle-Invasive Urothelial Carcinoma (MIUC) (INTerpath-005)
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.
Read the detailed description
Enrollment of participants into the Phase 1 Perioperative Cohort of this study is planned to start in approximately April of 2025.
- Conditions
- Bladder Cancer
- Being tested
- Pembrolizumab, Intismeran autogene, Placebo, Enfortumab Vedotin, Surgery (RC plus PLND)
- Keywords
- Programmed Cell Death-1 (PD1, PD-1), Programmed Cell Death 1 Ligand 1 (PDL1, PD-L1), Programmed Cell Death 1 Ligand 2 (PDL2, PD-L2)
- Medical subject headings
- Urinary Bladder Neoplasms, Parkinson Disease 4, Autosomal Dominant Lewy Body
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PembrolizumabBiological
Also called MK-3475, Keytruda®
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
Also called V940
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
Also called PADCEV®
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 or surgery
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.
| Study group | Role | What they receive |
|---|---|---|
| Adjuvant Cohort: Pembrolizumab + Intismeran autogene | Experimental | 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. Receives: Biological: Pembrolizumab; Biological: Intismeran autogene |
| Adjuvant Cohort: Pembrolizumab + Placebo | Active comparator | 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. Receives: Biological: Pembrolizumab; Other: Placebo |
| Perioperative Cohort: Pembrolizumab + Intismeran autogene + EV and Surgery | Experimental | 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. Receives: Biological: Pembrolizumab; Biological: Intismeran autogene; Biological: Enfortumab Vedotin; Procedure: Surgery (RC plus PLND) |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: 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.
Measured: Up to approximately 16 months
Secondary outcomes (6)
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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: Up to approximately 18 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Mar 2024
- Study start28 Mar 2024
- Primary completion23 Apr 2027 (estimated)
- Study completion20 Oct 2031 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Bladder CancerStudies of the same condition, open and under way.
- More trials run by Merck Sharp & Dohme LLCThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- The Phase 2 Adjuvant Cohort is a placebo- and active-controlled, parallel-group, multicenter, double-blind safety and efficacy study of adjuvant intismeran autogene plus pembrolizumab versus adjuvant placebo plus pembrolizumab in participants with pathologic high-risk MIUC after radical resection. Eligible participants will be randomly assigned in a 1:1 ratio to receive treatment with either intismeran autogene plus pembrolizumab or placebo plus pembrolizumab. The Phase 1 Perioperative Cohort of this study has a single arm into which eligible participants are allocated. It will evaluate safety and preliminary efficacy of perioperative (neoadjuvant and adjuvant) intismeran autogene in combination with pembrolizumab plus EV for participants with muscle-invasive bladder cancer (MIBC).
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 230 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Merck Sharp & Dohme LLC
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- ModernaTX, Inc.
- Responsible party
- Sponsor
- Investigators
- Medical Director, Study director, Merck Sharp & Dohme LLC
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06305767
- Sponsor's protocol ID
- V940-005
- Other IDs
- V940-005, U1111-1292-1952, 2023-505658-17-00, INTerpath-005, 2023
- Status last verified
- Jan 2026
- First submitted
- 5 Mar 2024
- Last updated
- 13 Jan 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: https://trialstransparency.msdclinicaltrials.com/pdf/ProcedureAccessClinicalTrialData.pdf
Study at a glance
From the registry record, last updated by the sponsor on 13 Jan 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1/2 Study of V940 Plus Pembrolizumab With or Without Enfortumab Vedotin in Muscle-Invasive Urothelial Carcinoma (MIUC) (INTerpath-005)
- ClinicalTrials.gov ID
- NCT06305767
- Acronym / sponsor ID
- V940-005
- Conditions
- Bladder Cancer
- Keywords
- Programmed Cell Death-1 (PD1, PD-1), Programmed Cell Death 1 Ligand 1 (PDL1, PD-L1), Programmed Cell Death 1 Ligand 2 (PDL2, PD-L2)
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 230 participants (estimated)
- Lead sponsor
- Merck Sharp & Dohme LLCIndustry (pharma, biotech, devices)
- Collaborators
- ModernaTX, Inc.
- Study start
- 28 Mar 2024 (actual)
- Primary completion
- 23 Apr 2027 (estimated)
- Study completion
- 20 Oct 2031 (estimated)
- First posted
- 12 Mar 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 3
- Model description
- The Phase 2 Adjuvant Cohort is a placebo- and active-controlled, parallel-group, multicenter, double-blind safety and efficacy study of adjuvant intismeran autogene plus pembrolizumab versus adjuvant placebo plus pembrolizumab in participants with pathologic high-risk MIUC after radical resection. Eligible participants will be randomly assigned in a 1:1 ratio to receive treatment with either intismeran autogene plus pembrolizumab or placebo plus pembrolizumab. The Phase 1 Perioperative Cohort of this study has a single arm into which eligible participants are allocated. It will evaluate safety and preliminary efficacy of perioperative (neoadjuvant and adjuvant) intismeran autogene in combination with pembrolizumab plus EV for participants with muscle-invasive bladder cancer (MIBC).
| Arm | Type | Receives |
|---|---|---|
| Adjuvant Cohort: Pembrolizumab + Intismeran autogene | Experimental | Biological: Pembrolizumab, Biological: Intismeran autogeneAdjuvant 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 | Active comparator | Biological: Pembrolizumab, Other: PlaceboAdjuvant 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 | Experimental | Biological: Pembrolizumab, Biological: Intismeran autogene, Biological: Enfortumab Vedotin, Procedure: 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (13 listed)
- 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
- Has MIUC
Key exclusion criteria (15 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| PembrolizumabAlso: MK-3475, Keytruda®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. | Biological | Adjuvant Cohort: Pembrolizumab + Intismeran autogene, Adjuvant Cohort: Pembrolizumab + Placebo, Perioperative Cohort: Pembrolizumab + Intismeran autogene + EV and Surgery |
| Intismeran autogeneAlso: V940Administered 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. | Biological | Adjuvant Cohort: Pembrolizumab + Intismeran autogene, Perioperative Cohort: Pembrolizumab + Intismeran autogene + EV and Surgery |
| PlaceboIntismeran autogene diluent only (saline and/or dextrose) administered via IM injection Q3W for up to 9 doses. | Other | Adjuvant Cohort: Pembrolizumab + Placebo |
| Enfortumab VedotinAlso: PADCEV®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. | Biological | Perioperative Cohort: Pembrolizumab + Intismeran autogene + EV and Surgery |
| Surgery (RC plus PLND)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. | Procedure or surgery | Perioperative Cohort: Pembrolizumab + Intismeran autogene + EV and Surgery |
Primary outcome
Adjuvant Cohort: Disease Free Survival (DFS)
Time frame: 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)
Time frame: 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
Time frame: 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.
6 secondary outcomes
Adjuvant Cohort: Overall Survival (OS)
Time frame: Up to approximately 28 months
Adjuvant Cohort: Distant Metastasis-Free Survival (DMFS)
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
Time frame: Up to approximately 13 months
Perioperative Cohort: Pathologic Complete Response (pCR) Rate
Time frame: Up to approximately 18 weeks
Perioperative Cohort: Pathologic Downstaging (pDS) Rate
Time frame: Up to approximately 18 weeks
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Jan 2026.
- Merck Clinical Trials InformationLink provided by the sponsor.
- Individual participant dataSharing planned: Yes. https://trialstransparency.msdclinicaltrials.com/pdf/ProcedureAccessClinicalTrialData.pdf
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Medical Director study director
Merck Sharp & Dohme LLC
74 sites in 16 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Pembrolizumab, Intismeran autogene and Enfortumab Vedotin in people with Bladder Cancer, run by Merck Sharp & Dohme LLC at 74 sites in 16 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 13 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 13 Jan 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 74 sites in United States, Turkey (Türkiye), Canada, Chile, France and 11 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Adjuvant Cohort: Disease Free Survival (DFS) (time frame: Up to approximately 28 months). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Jan 2026.