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

NCT06305767 | Active Not Recruiting Phase 1 FDA Drug

• 4 other identifiers: V940-005U1111-1292-19522023-505658-17-00INTerpath-005
• Study Type: interventional
• Target: 230
• Locations: 16 countries
• Sites: 74

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.

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)

Outcome Measures

Primary Outcomes (3)

• 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 Outcomes (6)

• Adjuvant Cohort: Overall Survival (OS)

  Up to approximately 28 months

• Adjuvant Cohort: Distant Metastasis-Free Survival (DMFS)

  Up to approximately 28 months

• Adjuvant Cohort: Number of Participants Who Experience an AE

  Up to approximately 16 months

• Adjuvant Cohort: Number of Participants Who Discontinue Study Treatment Due to an AE

  Up to approximately 13 months

• Perioperative Cohort: Pathologic Complete Response (pCR) Rate

  Up to approximately 18 weeks

Study Arms (3)

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.

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.

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.

Biological: Pembrolizumab; Biological: Intismeran autogene; Biological: Enfortumab Vedotin; Procedure: Surgery (RC plus PLND)

Interventions

Pembrolizumab BIOLOGICAL

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.

Also known as: MK-3475, Keytruda®

Adjuvant Cohort: Pembrolizumab + Intismeran autogene; Adjuvant Cohort: Pembrolizumab + Placebo; Perioperative Cohort: Pembrolizumab + Intismeran autogene + EV and Surgery

Intismeran autogene BIOLOGICAL

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.

Also known as: V940

Adjuvant Cohort: Pembrolizumab + Intismeran autogene; Perioperative Cohort: Pembrolizumab + Intismeran autogene + EV and Surgery

Placebo OTHER

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

Adjuvant Cohort: Pembrolizumab + Placebo

Enfortumab Vedotin BIOLOGICAL

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.

Also known as: PADCEV®

Perioperative Cohort: Pembrolizumab + Intismeran autogene + EV and Surgery

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.

Perioperative Cohort: Pembrolizumab + Intismeran autogene + EV and Surgery

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Merck Sharp & Dohme LLC: lead
• ModernaTX, Inc.: collaborator

Study Sites (74)

UCLA Hematology/Oncology - Westwood (Building 200 Suite 140)-Department of Urology/Institute of Uro ( Site 0104)

Los Angeles, California, 90095, United States

Location

AdventHealth Orlando-AdventHealth Medical Group Hematology & Oncology at Orlandoc ( Site 0102)

Orlando, Florida, 32804, United States

Location

University of Chicago Medical Center ( Site 0109)

Chicago, Illinois, 60637, United States

Location

University of Iowa ( Site 0110)

Iowa City, Iowa, 52242, United States

Location

Icahn School of Medicine at Mount Sinai ( Site 0101)

New York, New York, 10029, United States

Location

Duke Cancer Institute ( Site 0107)

Durham, North Carolina, 27710, United States

Location

Cleveland Clinic Main ( Site 0100)

Cleveland, Ohio, 44195, United States

Location

Fox Chase Cancer Center ( Site 0106)

Philadelphia, Pennsylvania, 19111, United States

Location

UT Southwestern Medical Center ( Site 0103)

Dallas, Texas, 75390, United States

Location

Houston Methodist Hospital-Department of Urology ( Site 0111)

Houston, Texas, 77030, United States

Location

Macquarie University-MQ Health Clinical Trials Unit ( Site 1803)

Macquarie University, New South Wales, 2109, Australia

Location

Westmead Hospital ( Site 1802)

Westmead, New South Wales, 2145, Australia

Location

Mater Misericordiae Limited ( Site 1808)

South Brisbane, Queensland, 4101, Australia

Location

One Clinical Research ( Site 1807)

Nedlands, Western Australia, 6009, Australia

Location

BC Cancer Vancouver ( Site 0004)

Vancouver, British Columbia, V5Z 4E6, Canada

Location

Princess Margaret Cancer Centre ( Site 0003)

Toronto, Ontario, M5G 2M9, Canada

Location

Centre Hospitalier de l'Université de Montréal ( Site 0005)

Montreal, Quebec, H2X 3E4, Canada

Location

Centre intégré de cancérologie du CHU de Québec Université Laval, Hôpital de l'Enfant-Jésus ( Site 0001)

Québec, Quebec, G1J 1Z4, Canada

Location

Centre intégré universitaire de santé et de services sociaux de l'Estrie - Centre Hospitalier Univer ( Site 0002)

Sherbrooke, Quebec, J1H 5H4, Canada

Location

Bradfordhill-Clinical Area ( Site 1501)

Recoleta, Santiago, Region M. de Santiago, 8420383, Chile

Location

FALP ( Site 1500)

Santiago, Region M. de Santiago, 7500921, Chile

Location

Pontificia Universidad Catolica de Chile ( Site 1503)

Santiago, Region M. de Santiago, 832000, Chile

Location

CIDO SpA ( Site 1509)

Temuco, Región de la Araucanía, 4810148, Chile

Location

ONCOCENTRO APYS-ACEREY ( Site 1506)

Viña del Mar, Región de Valparaíso, 2520598, Chile

Location

Clínica Universitaria Colombia ( Site 1600)

Bogotá, Bogota D.C., 111321, Colombia

Location

Sociedad De Oncologia Y Hematologia Del Cesar-Oncology ( Site 1605)

Valledupar, Cesar Department, 200001, Colombia

Location

Instituto Nacional De Cancerologia-Oncología Clínica ( Site 1606)

Bogota, Cundinamarca, 111151, Colombia

Location

Fundacion Valle del Lili- CIC-Oncology CIC ( Site 1608)

Cali, Valle del Cauca Department, 760032, Colombia

Location

Oncopole Claudius Regaud ( Site 0302)

Toulouse, Haute-Garonne, 31059, France

Location

Institut de Cancérologie de l'Ouest ( Site 0300)

Angers, Maine-et-Loire, 49055, France

Location

Hopital Claude Huriez - CHU de Lille ( Site 0301)

Lille, Nord, 59037, France

Location

Hôpital Saint-Louis ( Site 0304)

Paris, 75475, France

Location

Gustave Roussy ( Site 0303)

Villejuif, Île-de-France Region, 94805, France

Location

klinikum rechts der isar der technischen universität münchen-Urologische Klinik und Poliklinik ( Site 0401)

Munich, Bavaria, 81675, Germany

Location

Caritas-Krankenhaus St. Josef-Klinik fuer Urologie ( Site 0404)

Regensburg, Bavaria, 93053, Germany

Location

Universitaetsklinikum Carl Gustav Carus Dresden-Klinik und Poliklinik für Urologie ( Site 0405)

Dresden, Saxony, 01307, Germany

Location

Universitätsklinikum Halle-Universitätsklinik und Poliklinik für Urologie ( Site 0402)

Halle, Saxony-Anhalt, 06120, Germany

Location

Charité Universitaetsmedizin Berlin - Campus Mitte ( Site 0400)

Berlin, 10117, Germany

Location

Fondazione Policlinico Universitario Agostino Gemelli IRCCS -Medical Oncology ( Site 0504)

Rome, Lazio, 00168, Italy

Location

Ospedale San Martino-U.O. Oncologia Medica 1 ( Site 0500)

Genoa, Liguria, 16132, Italy

Location

Fondazione IRCCS Istituto Nazionale dei Tumori-Struttura Complessa Oncologia Medica 1 ( Site 0502)

Milan, Lombardy, 20133, Italy

Location

Azienda Ospedaliera Di Rilievo Nazionale A. Cardarelli-UOSC Oncologia ( Site 0503)

Naples, Napoli, 80131, Italy

Location

Ospedale San Raffaele-Oncologia Medica ( Site 0501)

Milan, 20132, Italy

Location

Auckland City Hospital ( Site 1901)

Auckland, 1023, New Zealand

Location

IPOR Instituto Peruano de Oncología & Radioterapia ( Site 1702)

Lima, 15036, Peru

Location

Oncosalud ( Site 1701)

Lima, 15036, Peru

Location

Hospital Militar Central Luis Arias Schereiber ( Site 1700)

Lima, 1507, Peru

Location

Clinical Research Center Spółka z ograniczoną odpowiedzialnością MEDIC-R Sp.k ( Site 0805)

Poznan, Greater Poland Voivodeship, WLK 61-731, Poland

Location

Centrum Onkologii im. Prof. Franciszka Lukaszczyka-Ambulatorium Chemioterapii ( Site 0801)

Bydgoszcz, Kuyavian-Pomeranian Voivodeship, 85-796, Poland

Location

Narodowy Instytut Onkologii im. Marii Sklodowskiej-Curie - P-Klinika Nowotworów Układu Moczowego ( Site 0800)

Warsaw, Masovian Voivodeship, 02-781, Poland

Location

Oddzial Onkologii Klinicznej z Pododdzialem Chemioterapii Jednodniowej ( Site 0802)

Koszalin, West Pomeranian Voivodeship, 75-581, Poland

Location

Swietokrzyskie Centrum Onkologii, Samodzielny Publiczny Zaklad Opieki Zdrowotnej ( Site 0806)

Kielce, Świętokrzyskie Voivodeship, SWK 25-734, Poland

Location

Korea University Anam Hospital ( Site 2002)

Seoul, 02841, South Korea

Location

Seoul National University Hospital-Urology ( Site 2000)

Seoul, 03080, South Korea

Location

Samsung Medical Center-Urology ( Site 2001)

Seoul, 06351, South Korea

Location

Hospital Germans Trias i Pujol-Instituto Catalán de Oncología de Badalona ( Site 1006)

Badalona, Barcelona, 08916, Spain

Location

HOSPITAL UNIVERSITARIO QUIRONSALUD MADRID-ONCOLOGIA MEDICA ( Site 1003)

Pozuelo de Alarcón, Madrid, 28223, Spain

Location

Hospital Universitario Ramón y Cajal-Medical Oncology ( Site 1005)

Madrid, Madrid, Comunidad de, 28034, Spain

Location

Hospital Universitari Vall d'Hebron-Oncology ( Site 1002)

Barcelona, 08035, Spain

Location

HOSPITAL UNIVERSITARIO VIRGEN DEL ROCIO-Medical Oncology ( Site 1001)

Seville, 41013, Spain

Location

Karolinska Universitetssjukhuset Solna ( Site 1101)

Stockholm, Stockholm County, 171 64, Sweden

Location

Akademiska sjukhuset-Blod- och tumörsjukdomar ( Site 1102)

Uppsala, Uppsala County, 751 85, Sweden

Location

Hacettepe Universite Hastaneleri-oncology hospital ( Site 1200)

Ankara, 06230, Turkey (Türkiye)

Location

Memorial Ankara Hastanesi-Medical Oncology ( Site 1204)

Ankara, 06520, Turkey (Türkiye)

Location

Ankara Bilkent Şehir Hastanesi-Medical Oncology ( Site 1201)

Ankara, 06800, Turkey (Türkiye)

Location

Koc Universitesi Hastanesi ( Site 1206)

Istanbul, 34025, Turkey (Türkiye)

Location

T.C. Saglik Bakanligi Turkiye Kamu Hastaneleri Kurumu - Baki-Istanbul Bakirkoy Sadi Konuk Training ( Site 1205)

Istanbul, 34147, Turkey (Türkiye)

Location

TC Saglik Bakanligi Goztepe Prof. Dr. Suleyman Yalcin Sehir Hastanesi-oncology ( Site 1202)

Istanbul, 34722, Turkey (Türkiye)

Location

Ege Universitesi Hastanesi-Medical Oncology ( Site 1203)

Izmir, 35100, Turkey (Türkiye)

Location

Torbay Hospital ( Site 1303)

Torquay, Devon, TQ2 7AA, United Kingdom

Location

Royal Free Hospital ( Site 1300)

London, England, NW3 2QG, United Kingdom

Location

Gartnavel General Hospital-Clinical Trials Unit ( Site 1301)

Glasgow, Glasgow City, G12 0YN, United Kingdom

Location

St Bartholomew's Hospital-Centre for Experimental Cancer Medicine ( Site 1302)

London, London, City of, EC1A 7BE, United Kingdom

Location

The Christie NHS Foundation Trust ( Site 1306)

Manchester, M20 4BX, United Kingdom

Location

Related Links

• Merck Clinical Trials Information
• Plain Language Summary

MeSH Terms

Conditions

Urinary Bladder Neoplasms; Parkinson Disease 4, Autosomal Dominant Lewy Body

Interventions

pembrolizumab; enfortumab vedotin; Surgical Procedures, Operative

Condition Hierarchy (Ancestors)

Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Urinary Bladder Diseases; Urologic Diseases; Male Urogenital Diseases

Study Officials

• Medical Director

  Merck Sharp & Dohme LLC

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: The Phase 2 Adjuvant Cohort of study will be conducted as a double-blind study under in-house blinding procedures. Intismeran autogene and placebo will be prepared and dispensed by unblinded pharmacists and administered in a blinded fashion by blinded personnel. The participants and the investigators who are involved in the study intervention administration will be unaware of the intervention assignments. The Phase 1 Perioperative Cohort will be conducted as an open-label study. Participants and investigators will be aware of the intervention assignments.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: 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).

Study Record Dates

• First Submitted: March 5, 2024
• First Posted: March 12, 2024
• Study Start: March 28, 2024
• Primary Completion (Estimated): April 23, 2027
• Study Completion (Estimated): October 20, 2031
• Last Updated: January 13, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will share

Locations

AU (4); GB (5); DE (5); NZ (1); KR (3); US (10); PE (3); ES (5); IT (5); PL (5); CL (5); CA (5); SE (2); CO (4); TU (7); FR (5)