Clinical trial NCT06305767: A Clinical Study of Intismeran Autogene (V940) Treatment and Pembrolizumab in People With Bladder Cancer (V940-005/INTerpath-005)
Official title: A Phase 1/2 Study of V940 Plus Pembrolizumab With or Without Enfortumab Vedotin in Muscle-Invasive Urothelial Carcinoma (MIUC) (INTerpath-005)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
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)
Lead sponsor: Merck Sharp & Dohme LLC
Sponsor class: INDUSTRY
Collaborators: name: ModernaTX, Inc.
First posted: 2024-03-12
Enrollment: 230
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention 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).
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Adjuvant Cohort: Disease Free Survival (DFS)
timeFrame: Up to approximately 28 months
measure: Perioperative Cohort: Number of Participants Who Experience an Adverse Event (AE)
timeFrame: Up to approximately 19 months
measure: Perioperative Cohort: Number of Participants Who Discontinue Study Treatment Due to AE
timeFrame: Up to approximately 16 months
Secondary outcomes:
measure: Adjuvant Cohort: Overall Survival (OS)
timeFrame: Up to approximately 28 months
measure: Adjuvant Cohort: Distant Metastasis-Free Survival (DMFS)
timeFrame: Up to approximately 28 months
measure: Adjuvant Cohort: Number of Participants Who Experience an AE
timeFrame: Up to approximately 16 months
measure: Adjuvant Cohort: Number of Participants Who Discontinue Study Treatment Due to an AE
timeFrame: Up to approximately 13 months
measure: Perioperative Cohort: Pathologic Complete Response (pCR) Rate
timeFrame: Up to approximately 18 weeks
measure: Perioperative Cohort: Pathologic Downstaging (pDS) Rate
timeFrame: Up to approximately 18 weeks
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: UCLA Hematology/Oncology - Westwood (Building 200 Suite 140)-Department of Urology/Institute of Uro ( Site 0104)
state: California
city: Orlando
country: United States
facility: AdventHealth Orlando-AdventHealth Medical Group Hematology & Oncology at Orlandoc ( Site 0102)
state: Florida
city: Chicago
country: United States
facility: University of Chicago Medical Center ( Site 0109)
state: Illinois
city: Iowa City
country: United States
facility: University of Iowa ( Site 0110)
state: Iowa
city: New York
country: United States
facility: Icahn School of Medicine at Mount Sinai ( Site 0101)
state: New York
city: Durham
country: United States
facility: Duke Cancer Institute ( Site 0107)
state: North Carolina
city: Cleveland
country: United States
facility: Cleveland Clinic Main ( Site 0100)
state: Ohio
city: Philadelphia
country: United States
facility: Fox Chase Cancer Center ( Site 0106)
state: Pennsylvania
city: Dallas
country: United States
facility: UT Southwestern Medical Center ( Site 0103)
state: Texas
city: Houston
country: United States
facility: Houston Methodist Hospital-Department of Urology ( Site 0111)
state: Texas
city: Macquarie University
country: Australia
facility: Macquarie University-MQ Health Clinical Trials Unit ( Site 1803)
state: New South Wales
city: Westmead
country: Australia
facility: Westmead Hospital ( Site 1802)
state: New South Wales
city: South Brisbane
country: Australia
facility: Mater Misericordiae Limited ( Site 1808)
state: Queensland
city: Nedlands
country: Australia
facility: One Clinical Research ( Site 1807)
state: Western Australia
city: Vancouver
country: Canada
facility: BC Cancer Vancouver ( Site 0004)
state: British Columbia
city: Toronto
country: Canada
facility: Princess Margaret Cancer Centre ( Site 0003)
state: Ontario
city: Montréal
country: Canada
facility: Centre Hospitalier de l'Université de Montréal ( Site 0005)
state: Quebec
city: Quebec City
country: Canada
facility: Centre intégré de cancérologie du CHU de Québec Université Laval, Hôpital de l'Enfant-Jésus ( Site 0001)
state: Quebec
city: Sherbrooke
country: Canada
facility: Centre intégré universitaire de santé et de services sociaux de l'Estrie - Centre Hospitalier Univer ( Site 0002)
state: Quebec
city: Temuco
country: Chile
facility: CIDO SpA ( Site 1509)
state: Araucania
city: Recoleta, Santiago
country: Chile
facility: Bradfordhill-Clinical Area ( Site 1501)
state: Region M. De Santiago
city: Santiago
country: Chile
facility: FALP ( Site 1500)
state: Region M. De Santiago
city: Santiago
country: Chile
facility: Pontificia Universidad Catolica de Chile-Centro del Cáncer ( Site 1503)
state: Region M. De Santiago
city: Viña del Mar
country: Chile
facility: ONCOCENTRO APYS-ACEREY ( Site 1506)
state: Valparaiso
city: Valledupar
country: Colombia
facility: Sociedad De Oncologia Y Hematologia Del Cesar-Oncology ( Site 1605)
state: Cesar
city: Bogota
country: Colombia
facility: Instituto Nacional De Cancerologia-Oncología Clínica ( Site 1606)
state: Cundinamarca
city: Bogotá
country: Colombia
facility: Clínica Universitaria Colombia ( Site 1600)
state: Distrito Capital De Bogota
city: Cali
country: Colombia
facility: Fundacion Valle del Lili- CIC-Oncology CIC ( Site 1608)
state: Valle Del Cauca
city: Toulouse
country: France
facility: Oncopole Claudius Regaud ( Site 0302)
state: Haute-Garonne
city: Villejuif
country: France
facility: Gustave Roussy ( Site 0303)
state: Ile-de-France
city: ANGERS cedex 02
country: France
facility: Institut de Cancérologie de l'Ouest ( Site 0300)
state: Maine-et-Loire
city: Lille
country: France
facility: Hopital Claude Huriez - CHU de Lille ( Site 0301)
state: Nord
city: Paris
country: France
facility: Hôpital Saint-Louis ( Site 0304)
city: Munich
country: Germany
facility: klinikum rechts der isar der technischen universität münchen-Urologische Klinik und Poliklinik ( Site 0401)
state: Bayern
city: Regensburg
country: Germany
facility: Caritas-Krankenhaus St. Josef-Klinik fuer Urologie ( Site 0404)
state: Bayern
city: Halle
country: Germany
facility: Universitätsklinikum Halle-Universitätsklinik und Poliklinik für Urologie ( Site 0402)
state: Sachsen-Anhalt
city: Dresden
country: Germany
facility: Universitaetsklinikum Carl Gustav Carus Dresden-Klinik und Poliklinik für Urologie ( Site 0405)
state: Sachsen
city: Berlin
country: Germany
facility: Charité Universitaetsmedizin Berlin - Campus Mitte ( Site 0400)
city: Roma
country: Italy
facility: Fondazione Policlinico Universitario Agostino Gemelli IRCCS -Medical Oncology ( Site 0504)
state: Lazio
city: Genova
country: Italy
facility: Ospedale San Martino-U.O. Oncologia Medica 1 ( Site 0500)
state: Liguria
city: Milan
country: Italy
facility: Fondazione IRCCS Istituto Nazionale dei Tumori-Struttura Complessa Oncologia Medica 1 ( Site 0502)
state: Lombardia
city: Naples
country: Italy
facility: Azienda Ospedaliera Di Rilievo Nazionale A. Cardarelli-UOSC Oncologia ( Site 0503)
state: Napoli
city: Milano
country: Italy
facility: Ospedale San Raffaele-Oncologia Medica ( Site 0501)
city: Seoul
country: Korea, Republic of
facility: Korea University Anam Hospital ( Site 2002)
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital-Urology ( Site 2000)
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center-Urology ( Site 2001)
city: Auckland
country: New Zealand
facility: Auckland City Hospital ( Site 1901)
city: Lima
country: Peru
facility: IPOR Instituto Peruano de Oncología & Radioterapia ( Site 1702)
city: Lima
country: Peru
facility: Oncosalud ( Site 1701)
city: Lima
country: Peru
facility: Hospital Militar Central Luis Arias Schereiber ( Site 1700)
city: Bydgoszcz
country: Poland
facility: Centrum Onkologii im. Prof. Franciszka Lukaszczyka-Ambulatorium Chemioterapii ( Site 0801)
state: Kujawsko-pomorskie
city: Warszawa
country: Poland
facility: Narodowy Instytut Onkologii im. Marii Sklodowskiej-Curie - P-Klinika Nowotworów Układu Moczowego ( Site 0800)
state: Mazowieckie
city: Kielce
country: Poland
facility: Swietokrzyskie Centrum Onkologii, Samodzielny Publiczny Zaklad Opieki Zdrowotnej ( Site 0806)
state: Swietokrzyskie
city: Poznan
country: Poland
facility: Clinical Research Center Spółka z ograniczoną odpowiedzialnością MEDIC-R Sp.k ( Site 0805)
state: Wielkopolskie
city: Koszalin
country: Poland
facility: Szpital Wojewódzki im. Mikoaja Kopernika w Koszalinie-Oddzial Dzienny Chemioterapii ( Site 0802)
state: Zachodniopomorskie
city: Badalona
country: Spain
facility: Hospital Germans Trias i Pujol-Instituto Catalán de Oncología de Badalona ( Site 1006)
state: Barcelona
city: Madrid
country: Spain
facility: Hospital Universitario Ramón y Cajal-Medical Oncology ( Site 1005)
state: Madrid, Comunidad De
city: Pozuelo de Alarcon
country: Spain
facility: HOSPITAL UNIVERSITARIO QUIRONSALUD MADRID-ONCOLOGIA MEDICA ( Site 1003)
state: Madrid
city: Barcelona
country: Spain
facility: Hospital Universitari Vall d'Hebron-Oncology ( Site 1002)
city: Sevilla
country: Spain
facility: HOSPITAL UNIVERSITARIO VIRGEN DEL ROCIO-Medical Oncology ( Site 1001)
city: Stockholm
country: Sweden
facility: Karolinska Universitetssjukhuset Solna ( Site 1101)
state: Stockholms Lan
city: Uppsala
country: Sweden
facility: Akademiska sjukhuset-Blod- och tumörsjukdomar ( Site 1102)
state: Uppsala Lan
city: Ankara
country: Turkey
facility: Hacettepe Universite Hastaneleri-oncology hospital ( Site 1200)
city: Ankara
country: Turkey
facility: Memorial Ankara Hastanesi-Medical Oncology ( Site 1204)
city: Ankara
country: Turkey
facility: Ankara Bilkent Şehir Hastanesi-Medical Oncology ( Site 1201)
city: Istanbul
country: Turkey
facility: Koc Universitesi Hastanesi ( Site 1206)
city: Istanbul
country: Turkey
facility: T.C. Saglik Bakanligi Turkiye Kamu Hastaneleri Kurumu - Baki-Istanbul Bakirkoy Sadi Konuk Training ( Site 1205)
city: Istanbul
country: Turkey
facility: TC Saglik Bakanligi Goztepe Prof. Dr. Suleyman Yalcin Sehir Hastanesi-oncology ( Site 1202)
city: Izmir
country: Turkey
facility: Ege Universitesi Hastanesi-Medical Oncology ( Site 1203)
city: Torquay
country: United Kingdom
facility: Torbay Hospital ( Site 1303)
state: Devon
city: London
country: United Kingdom
facility: Royal Free Hospital ( Site 1300)
state: England
city: Glasgow
country: United Kingdom
facility: Gartnavel General Hospital-Clinical Trials Unit ( Site 1301)
state: Glasgow City
city: London
country: United Kingdom
facility: St Bartholomew's Hospital-Centre for Experimental Cancer Medicine ( Site 1302)
state: London, City Of
city: Manchester
country: United Kingdom
facility: The Christie NHS Foundation Trust ( Site 1306)
Study officials:
affiliation: Merck Sharp & Dohme LLC
name: Medical Director
role: STUDY_DIRECTOR
References: