A Study of (Neo)Adjuvant Intismeran Autogene (V940) and Pembrolizumab in Cutaneous Squamous Cell Carcinoma (V940-007)

NCT ID: NCT06295809

Last Updated: 2025-12-09

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

ACTIVE_NOT_RECRUITING

Clinical Phase

PHASE2/PHASE3

Total Enrollment

46 participants

Study Classification

INTERVENTIONAL

Study Start Date

2024-04-18

Study Completion Date

2026-03-05

Brief Summary

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This is a two-part (Phase 2/Phase 3) study of intismeran autogene, an individualized neoantigen therapy (INT), plus pembrolizumab in participants with locally resectable advanced cutaneous squamous cell carcinoma (LA cSCC). Phase 2 has three arms intismeran autogene plus pembrolizumab given as neoadjuvant and adjuvant treatment with standard of care (SOC), standard of care (surgical resection with/without adjuvant radiation therapy (RT) only at investigator's discretion) and pembrolizumab monotherapy given as neoadjuvant and adjuvant treatment with SOC. This phase will assess the safety and efficacy of intismeran autogene in combination with pembrolizumab as neoadjuvant and adjuvant therapy in participants with resectable LA cSCC as compared to standard of care SOC only. The primary hypothesis is that intismeran autogene plus pembrolizumab with SOC is superior to SOC only with respect to event free survival (EFS) as assessed by the investigator. Phase 3 expansion will be determined by prespecified Go-No-Go decision in which 412 additional participants will be randomized to intismeran autogene plus pembrolizumab with SOC and SOC only, without changing the inclusion/exclusion criteria for the additional enrollment or study endpoints.

As of Amendment 04, enrollment was stopped and there will be no Phase 3 expansion.

Detailed Description

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Conditions

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Carcinoma, Squamous Cell Skin Neoplasms

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

SINGLE

Outcome Assessors

Study Groups

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Pembrolizumab plus Intismeran autogene with SOC

Participants will receive intismeran autogene 1 mg intramuscular (IM) injection every 3 weeks (q3w) for up to 6 weeks and pembrolizumab 400 mg intravenous (IV) infusion every 6 weeks (q6w) up to 12 weeks as neoadjuvant therapy prior to surgery; followed by intismeran autogene 1 mg IM injection q3w up to 21 weeks.

Group Type EXPERIMENTAL

Pembrolizumab

Intervention Type BIOLOGICAL

IV Infusion

Intismeran autogene

Intervention Type BIOLOGICAL

IM injection

Surgery

Intervention Type PROCEDURE

Local resection of cancerous lesions of the skin

Standard of Care (SOC)

Participants will receive surgical resection as per local guidelines with/without adjuvant radiation therapy (RT) at investigator's discretion.

Group Type ACTIVE_COMPARATOR

Surgery

Intervention Type PROCEDURE

Local resection of cancerous lesions of the skin

Pembrolizumab with SOC

Participants will receive pembrolizumab 400 mg IV infusion q6w up to 12 weeks as neoadjuvant therapy prior to surgery.

Group Type EXPERIMENTAL

Pembrolizumab

Intervention Type BIOLOGICAL

IV Infusion

Surgery

Intervention Type PROCEDURE

Local resection of cancerous lesions of the skin

Interventions

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Pembrolizumab

IV Infusion

Intervention Type BIOLOGICAL

Intismeran autogene

IM injection

Intervention Type BIOLOGICAL

Surgery

Local resection of cancerous lesions of the skin

Intervention Type PROCEDURE

Other Intervention Names

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MK-3475 Keytruda® mRNA-4157 V940

Eligibility Criteria

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Inclusion Criteria

* Has a histologically confirmed diagnosis of resectable cSCC as the primary site of malignancy (metastatic skin involvement from another primary cancer or from an unknown primary cancer is not permitted).
* Has LA Stage II-IV (M0) cSCC without distant metastases.
* cSCC must be amenable to surgery (resectable) with curative intent.
* Has a formalin-fixed, paraffin-embedded (FFPE) tumor sample available or is able to provide one that is suitable for the Next-generation Sequencing (NGS) required for this study.
* For males, agrees to be abstinent from penile-vaginal intercourse OR agrees to use a highly effective contraceptive method while receiving adjuvant radiation therapy (RT), and for ≥3 months after the last dose of study intervention
* Is female and not pregnant/breastfeeding and at least one of the following applies during the study : is not a woman of childbearing potential (WOCBP), is a WOCBP and uses highly effective contraception (low user dependency method OR a user dependent hormonal method in combination with a barrier method) at least during use of intismeran autogene: 15 days, Pembrolizumab: 120 days, Adjuvant RT, if performed: 90 days after last exposure or is a WOCBP who is abstinent from heterosexual intercourse.
* Has measurable disease per RECIST 1.1 as assessed by the local site investigator/radiology.
* Has a life expectancy of \>3 months per investigator assessment.
* Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1 assessed within 14 days before randomization.
* Has adequate organ function.
* If hepatitis B surface antigen (HBsAg) positive, must have received hepatitis B virus (HBV) antiviral therapy for at least 4 weeks and have undetectable HBV viral load prior to randomization
* If there is a history of hepatitis C virus (HCV) infection, HCV viral load must be undetectable at screening
* If human immunodeficiency virus (HIV)-infected, must have well controlled HIV on antiretroviral therapy (ART)

Exclusion Criteria

* Has any other histologic type of skin cancer other than invasive cSCC as well as mixed histology, eg, basal cell carcinoma that has not been definitively treated with surgery or radiation, Bowen's disease, Merkel cell carcinoma (MCC), or melanoma
* Has distant metastatic disease (M1), visceral and/or distant nodal
* Has received prior therapy with an anti-programmed cell death receptor 1 (anti-PD-1), anti-programmed cell death receptor ligand 1 (anti-PD-L1), or anti-programmed cell death receptor ligand 2 (anti-PD-L2) agent, or with an agent directed to another stimulatory or coinhibitory T-cell receptor (e.g., cytotoxic T-lymphocyte associated protein 4 (CTLA-4), OX-40, CD137)
* Has received prior systemic anticancer therapy including investigational agents for cSCC before randomization
* Has received prior radiotherapy within 2 weeks of start of study intervention, or has radiation-related toxicities, requiring corticosteroids
* Has received a live or live-attenuated vaccine within 30 days before the first dose of study intervention
* Has received transfusion of blood products (including platelets or red blood cells) or administration of colony stimulating factors (including granulocyte colony-stimulating factor, granulocyte macrophage colony-stimulating factor, or recombinant erythropoietin) within 2 weeks of the screening blood sample (including the NGS blood sample)
* Has received prior treatment with another cancer vaccine
* Has received prior radiotherapy to the index lesion (in-field lesion). Must have recovered from all radiation-related toxicities prior to randomization and not have had radiation pneumonitis
* Has received an investigational agent or has used an investigational device within 4 weeks prior to study intervention administration
* Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior the first dose of study medication
* Has a known additional malignancy that is progressing or has required active treatment within the past 2 years
* History of chronic lymphocytic leukemia (CLL)
* History of central nervous system (CNS) metastases and/or carcinomatous meningitis
* Has severe hypersensitivity (≥Grade 3) to either intismeran autogene or pembrolizumab and/or any of its excipients
* Has an active autoimmune disease that has required systemic treatment in the past 2 years. Replacement therapy (eg, thyroxine, insulin, or physiologic corticosteroid) is allowed
* History of (noninfectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease
* Has an active infection requiring systemic therapy
* Has HIV with a history of Kaposi's sarcoma and/or Multicentric Castleman's Disease
* Has concurrent active Hepatitis B (defined as HBsAg positive and/or detectable HBV DNA) and Hepatitis C virus (defined as anti-HCV Ab positive and detectable HCV RNA) infection
* Has had a myocardial infarction within 6 months of randomization
* History of allogeneic tissue/solid organ transplant
* Has not adequately recovered from major surgery or have ongoing surgical complications
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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ModernaTX, Inc.

INDUSTRY

Sponsor Role collaborator

Merck Sharp & Dohme LLC

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Medical Director

Role: STUDY_DIRECTOR

Merck Sharp & Dohme LLC

Locations

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USC/Norris Comprehensive Cancer Center ( Site 1112)

Los Angeles, California, United States

Site Status

Hoag Memorial Hospital Presbyterian ( Site 1122)

Newport Beach, California, United States

Site Status

Stanford Cancer Center ( Site 1109)

Palo Alto, California, United States

Site Status

University of California Davis (UC Davis) Comprehensive Cancer Center ( Site 1103)

Sacramento, California, United States

Site Status

Winship Cancer Institute, Emory University ( Site 1151)

Atlanta, Georgia, United States

Site Status

University of Iowa-Holden Comprehensive Cancer Center ( Site 1118)

Iowa City, Iowa, United States

Site Status

University of Kentucky Chandler Medical Center ( Site 1101)

Lexington, Kentucky, United States

Site Status

Ochsner Clinic Foundation ( Site 1113)

New Orleans, Louisiana, United States

Site Status

Massachusetts General Hospital ( Site 1162)

Boston, Massachusetts, United States

Site Status

Dana-Farber Cancer Institute ( Site 1130)

Boston, Massachusetts, United States

Site Status

Washington University School of Medicine-Internal Medicine/Oncology ( Site 1100)

St Louis, Missouri, United States

Site Status

John Theurer Cancer Center at Hackensack University Medical Center ( Site 1125)

Hackensack, New Jersey, United States

Site Status

Atlantic Health System Morristown Medical Center ( Site 1136)

Morristown, New Jersey, United States

Site Status

Perlmutter Cancer Center at NYU Langone Hospital - Long Island ( Site 1160)

Mineola, New York, United States

Site Status

Laura and Isaac Perlmutter Cancer Center ( Site 1121)

New York, New York, United States

Site Status

Providence Portland Medical Center ( Site 1102)

Portland, Oregon, United States

Site Status

UPMC Hillman Cancer Center ( Site 1107)

Pittsburgh, Pennsylvania, United States

Site Status

Avera Cancer Institute- Research ( Site 1161)

Sioux Falls, South Dakota, United States

Site Status

University of Virginia Health System ( Site 1115)

Charlottesville, Virginia, United States

Site Status

Inova Schar Cancer Institute ( Site 1108)

Fairfax, Virginia, United States

Site Status

University Hospital and UW Health Clinics ( Site 1119)

Madison, Wisconsin, United States

Site Status

Instituto de Investigaciones Clínicas Mar del Plata ( Site 1213)

Mar del Plata, Buenos Aires, Argentina

Site Status

Fundacion Estudios Clinicos-Oncology ( Site 1205)

Rosario, Santa Fe Province, Argentina

Site Status

Sanatorio Finochietto ( Site 1202)

Buenos Aires, , Argentina

Site Status

Investigaciones Clinicas Moleculares (ICM) ( Site 1212)

CABA, , Argentina

Site Status

Hospital Italiano de Córdoba ( Site 1204)

Córdoba, , Argentina

Site Status

Melanoma Institute Australia-Clinical Trials Unit ( Site 3205)

Wollstonecraft, New South Wales, Australia

Site Status

Sunshine Coast University Hospital-Medical Oncology ( Site 3212)

Birtinya, Queensland, Australia

Site Status

Royal Brisbane and Women's Hospital-Medical Oncology Clinical Trials Unit, Cancer Care Services ( Si

Brisbane, Queensland, Australia

Site Status

Gold Coast University Hospital-Cancer and Blood Disorders Clinical Trial Team ( Site 3207)

Gold Coast, Queensland, Australia

Site Status

Gallipoli Medical Research Ltd-GMRF CTU ( Site 3206)

Greenslopes, Queensland, Australia

Site Status

Austin Health ( Site 3209)

Heidelberg, Victoria, Australia

Site Status

One Clinical Research ( Site 3211)

Nedlands, Western Australia, Australia

Site Status

Cliniques universitaires Saint-Luc ( Site 1701)

Brussels, Bruxelles-Capitale, Region de, Belgium

Site Status

UZ Gent-Medical oncology ( Site 1702)

Ghent, Oost-Vlaanderen, Belgium

Site Status

Clinica Amo - Rio Vermelho-INSTITUTO ETICA ( Site 1315)

Salvador, Estado de Bahia, Brazil

Site Status

Hospital de Cancer de Londrina-Clinical Research Unit ( Site 1316)

Londrina, Paraná, Brazil

Site Status

Associação Hospitalar Beneficente São Vicente de Paulo-Instituto do Câncer ( Site 1309)

Passo Fundo, Rio Grande do Sul, Brazil

Site Status

Hospital Nossa Senhora da Conceição-Centro Integrado de Pesquisa em Oncologia ( Site 1300)

Porto Alegre, Rio Grande do Sul, Brazil

Site Status

ANIMI - Unidade de Tratamento Oncologico ( Site 1312)

Lages, Santa Catarina, Brazil

Site Status

Fundação Faculdade Regional de Medicina de São José do Rio Preto-Centro Integrado de Pesquisa ( Site

São José do Rio Preto, São Paulo, Brazil

Site Status

IPITEC ( Site 1313)

São Paulo, São Paulo, Brazil

Site Status

Jewish General Hospital ( Site 1009)

Montreal, Quebec, Canada

Site Status

Centre intégré universitaire de santé et de services sociaux de l'Estrie - Centre Hospitalier Univer

Sherbrooke, Quebec, Canada

Site Status

FALP-UIDO ( Site 1401)

Santiago, Region M. de Santiago, Chile

Site Status

Clínica Alemana de Santiago-Gynecology and Obstetrics ( Site 1410)

Santiago, Region M. de Santiago, Chile

Site Status

James Lind Centro de Investigacion del Cancer ( Site 1411)

Temuco, Región de la Araucanía, Chile

Site Status

CIDO SpA-Oncology ( Site 1405)

Temuco, Región de la Araucanía, Chile

Site Status

Fundacion Colombiana de Cancerología Clinica Vida ( Site 1501)

Medellín, Antioquia, Colombia

Site Status

Oncologos del Occidente ( Site 1504)

Pereira, Risaralda Department, Colombia

Site Status

Fundación Valle del Lili ( Site 1502)

Cali, Valle del Cauca Department, Colombia

Site Status

Vseobecna fakultni nemocnice v Praze-Department of Dermatology ( Site 1800)

Prague, Praha 2, Czechia

Site Status

CHU de Bordeaux Hop St ANDRE ( Site 1902)

Bordeaux, Aquitaine, France

Site Status

Assistance Publique Hôpitaux de Marseille - Hôpital de la Timone ( Site 1903)

Marseille, Bouches-du-Rhone, France

Site Status

Centre Hospitalier Universitaire Dijon Bourgogne - Hôpital François Mitterrand ( Site 1904)

Dijon, Bourgogne-Franche-Comté, France

Site Status

Institut Universitaire du Cancer Toulouse - Oncopole - CHU de TOULOUSE ( Site 1908)

Toulouse, Haute-Garonne, France

Site Status

Centre Hospitalier Universitaire de Nantes - L' Hopital l'hôtel-Dieu-Onco-Dermatology ( Site 1910)

Nantes, Loire-Atlantique, France

Site Status

Hopital Claude Huriez - CHU de Lille ( Site 1907)

Lille, Nord, France

Site Status

centre hospitalier lyon sud ( Site 1901)

Pierre-Bénite, Rhone, France

Site Status

Hôpital Saint-Louis ( Site 1906)

Paris, , France

Site Status

Gustave Roussy ( Site 1909)

Villejuif, Île-de-France Region, France

Site Status

NCT ( Site 2002)

Heidelberg, Baden-Wurttemberg, Germany

Site Status

Universitaetsklinikum Tuebingen-Hautklinik ( Site 2003)

Tübingen, Baden-Wurttemberg, Germany

Site Status

klinikum rechts der isar der technischen universität münchen ( Site 2009)

München, Bavaria, Germany

Site Status

Universitaetsklinikum Wuerzburg-Department of Dermatology ( Site 2001)

Würzburg, Bavaria, Germany

Site Status

Klinikum Dortmund Klinikzentrum Mitte ( Site 2008)

Dortmund, North Rhine-Westphalia, Germany

Site Status

Universitaetsklinikum Essen-Klinik für Dermatologie, Venerologie und Allergologie ( Site 2005)

Essen, North Rhine-Westphalia, Germany

Site Status

Universitätsmedizin Johannes Gutenberg Universität Mainz ( Site 2007)

Mainz, Rhineland-Palatinate, Germany

Site Status

Universitätsklinikum Schleswig-Holstein-Dermatology ( Site 2012)

Lübeck, Schleswig-Holstein, Germany

Site Status

Pécsi Tudományegyetem Klinikai Központ-Bőr-, Nemikórtani és Onkodermatológiai Klinika ( Site 2100)

Pécs, Baranya, Hungary

Site Status

Szegedi Tudományegyetem Szent-Györgyi Albert Klinikai Közpo-Department of Dermatology and Allergol

Szeged, Csongrád megye, Hungary

Site Status

Debreceni Egyetem Klinikai Kozpont-Bőrgyógyászati Klinika ( Site 2102)

Debrecen, , Hungary

Site Status

Gyor-Moson-Sopron Varmegyei Petz Aladar Egyetemi Oktato Korhaz- Onkoradiologiai Osztaly ( Site 2110)

Győr, , Hungary

Site Status

Emek Medical Center ( Site 2203)

Afula, , Israel

Site Status

Hadassah Medical Center ( Site 2201)

Jerusalem, , Israel

Site Status

Rabin Medical Center ( Site 2202)

Petah Tikva, , Israel

Site Status

Sheba Medical Center ( Site 2200)

Ramat Gan, , Israel

Site Status

Instituto Tumori Giovanni Paolo II ( Site 2301)

Bari, Apulia, Italy

Site Status

Ospedale San Martino-Oncologia Medica 2 ( Site 2303)

Genoa, Liguria, Italy

Site Status

Istituto Clinico Humanitas-U.O di Oncologia medica ed Ematologia ( Site 2304)

Rozzano, Milano, Italy

Site Status

Azienda Ospedaliero Universitaria Senese ( Site 2302)

Siena, Tuscany, Italy

Site Status

Azienda Socio Sanitaria Territoriale Papa Giovanni XXIII-UOC Oncologia ( Site 2305)

Bergamo, , Italy

Site Status

Istituto Nazionale Tumori IRCCS Fondazione Pascale-s.c. melanoma, immunoterapia oncologica e terapi

Napoli, , Italy

Site Status

Harbour Cancer & Wellness ( Site 3300)

Auckland, , New Zealand

Site Status

Oslo universitetssykehus, Radiumhospitalet ( Site 2400)

Oslo, , Norway

Site Status

Centrum Medyczne HCP ( Site 2505)

Poznan, Greater Poland Voivodeship, Poland

Site Status

Centrum Onkologii im. Prof. Franciszka Lukaszczyka-Ambulatorium Chemioterapii ( Site 2501)

Bydgoszcz, Kuyavian-Pomeranian Voivodeship, Poland

Site Status

Narodowy Instytut Onkologii im. Marii Sklodowskiej-Curie - Panstwowy Instytut Badawczy w Warszawie (

Warsaw, Masovian Voivodeship, Poland

Site Status

Uniwersyteckie Centrum Kliniczne-Early Clinical Trials Unit ( Site 2506)

Gdansk, Pomeranian Voivodeship, Poland

Site Status

Swietokrzyskie Centrum Onkologii, Samodzielny Publiczny Zakl-Klinika Onkologii Klinicznej, Dzial Ch

Kielce, Świętokrzyskie Voivodeship, Poland

Site Status

Spitalul Universitar de Urgență Elias ( Site 2600)

Bucharest, București, Romania

Site Status

SC Radiotherapy Center Cluj SRL-Oncologie Medicala ( Site 2602)

Florești, Cluj, Romania

Site Status

Centrul de Oncologie Sfantul Nectarie-Medical ( Site 2601)

Craiova, Dolj, Romania

Site Status

Sigmedical Services SRL ( Site 2603)

Suceava, , Romania

Site Status

Hospital Germans Trias i Pujol-Instituto Catalán de Oncología de Badalona ( Site 2804)

Badalona, Barcelona, Spain

Site Status

HOSPITAL CLÍNIC DE BARCELONA-ICHMO- Clinic Institut of Haematological and Oncological diseases ( Sit

Barcelona, Catalonia, Spain

Site Status

Centro Oncologico de Galicia ( Site 2806)

A Coruña, Galicia, Spain

Site Status

Hospital Universitario Ramón y Cajal-Medical Oncology ( Site 2801)

Madrid, Madrid, Comunidad de, Spain

Site Status

H.R.U Malaga - Hospital General ( Site 2805)

Málaga, Malaga, Spain

Site Status

Hospital General Universitario de Valencia-oncology service ( Site 2802)

Valencia, Valenciana, Comunitat, Spain

Site Status

Hospital Universitari Vall d'Hebron-Departamento de Oncologia- VHIO ( Site 2803)

Barcelona, , Spain

Site Status

Clinica Universidad de Navarra-Medical Oncology ( Site 2807)

Madrid, , Spain

Site Status

Addenbrooke's Hospital-Cambridge Cancer Trials Centre ( Site 3103)

Cambridge, Cambridgeshire, United Kingdom

Site Status

Derriford Hospital-Oncology ( Site 3104)

Plymouth, Devon, United Kingdom

Site Status

Castle Hill Hospital ( Site 3102)

Cottingham, East Riding Of Yorkshire, United Kingdom

Site Status

Singleton Hospital-South West Wales Cancer Institute ( Site 3100)

Swansea, , United Kingdom

Site Status

Countries

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United States Argentina Australia Belgium Brazil Canada Chile Colombia Czechia France Germany Hungary Israel Italy New Zealand Norway Poland Romania Spain United Kingdom

Related Links

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Other Identifiers

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2023-505712-37-00

Identifier Type: REGISTRY

Identifier Source: secondary_id

U1111-1292-3589

Identifier Type: REGISTRY

Identifier Source: secondary_id

V940

Identifier Type: OTHER

Identifier Source: secondary_id

V940-007

Identifier Type: -

Identifier Source: org_study_id

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