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

NCT06295809 | Completed Phase 2 FDA Drug

• 4 other identifiers: V940-0072023-505712-37-00U1111-1292-3589V940
• Study Type: interventional
• Target: 46
• Locations: 20 countries
• Sites: 106

Brief Summary

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.

Conditions

Skin Neoplasms; Carcinoma, Squamous Cell

Keywords

pembrolizumab

Outcome Measures

Primary Outcomes (1)

• Event Free Survival (EFS)

  EFS is defined as the time from randomization to any of the following events as assessed by the investigator: progression of disease that precludes surgery, or inability to undergo R0 or R1 surgical resection; disease recurrence (local, regional, or distant); new primary high-risk cSCC; death due to any cause. EFS will be presented.

  Up to ~22 months

Secondary Outcomes (8)

• Overall response rate (ORR)

  Up to ~22 months

• Freedom from surgery (FFS) rate

  Up to ~22 months

• Pathologic complete response (pCR) rate

  Up to ~22 months

• Major pathologic response (mPR) rate

  Up to ~22 months

• Disease-specific survival (DSS)

  Up to ~22 months

Study Arms (3)

Pembrolizumab plus Intismeran autogene with SOC

EXPERIMENTAL

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.

Biological: Pembrolizumab; Biological: Intismeran autogene; Procedure: Surgery

Standard of Care (SOC)

ACTIVE COMPARATOR

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

Procedure: Surgery

Pembrolizumab with SOC

EXPERIMENTAL

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

Biological: Pembrolizumab; Procedure: Surgery

Interventions

Pembrolizumab BIOLOGICAL

IV Infusion

Also known as: MK-3475, Keytruda®

Pembrolizumab plus Intismeran autogene with SOC; Pembrolizumab with SOC

Intismeran autogene BIOLOGICAL

IM injection

Also known as: mRNA-4157, V940

Pembrolizumab plus Intismeran autogene with SOC

Surgery PROCEDURE

Local resection of cancerous lesions of the skin

Pembrolizumab plus Intismeran autogene with SOC; Pembrolizumab with SOC; Standard of Care (SOC)

Eligibility Criteria

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

You may qualify if:

• 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)

You may not qualify if:

• 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

Sponsors & Collaborators

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

Study Sites (106)

USC/Norris Comprehensive Cancer Center ( Site 1112)

Los Angeles, California, 90033, United States

Location

Hoag Memorial Hospital Presbyterian ( Site 1122)

Newport Beach, California, 92663, United States

Location

Stanford Cancer Center ( Site 1109)

Palo Alto, California, 94304, United States

Location

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

Sacramento, California, 95817, United States

Location

Winship Cancer Institute, Emory University ( Site 1151)

Atlanta, Georgia, 30322, United States

Location

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

Iowa City, Iowa, 52242, United States

Location

University of Kentucky Chandler Medical Center ( Site 1101)

Lexington, Kentucky, 40536, United States

Location

Ochsner Clinic Foundation ( Site 1113)

New Orleans, Louisiana, 70121, United States

Location

Massachusetts General Hospital ( Site 1162)

Boston, Massachusetts, 02114, United States

Location

Dana-Farber Cancer Institute ( Site 1130)

Boston, Massachusetts, 02215, United States

Location

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

St Louis, Missouri, 63110, United States

Location

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

Hackensack, New Jersey, 07601, United States

Location

Atlantic Health System Morristown Medical Center ( Site 1136)

Morristown, New Jersey, 07960, United States

Location

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

Mineola, New York, 11501, United States

Location

Laura and Isaac Perlmutter Cancer Center ( Site 1121)

New York, New York, 10016, United States

Location

Providence Portland Medical Center ( Site 1102)

Portland, Oregon, 97213, United States

Location

UPMC Hillman Cancer Center ( Site 1107)

Pittsburgh, Pennsylvania, 15232, United States

Location

Avera Cancer Institute- Research ( Site 1161)

Sioux Falls, South Dakota, 57105, United States

Location

University of Virginia Health System ( Site 1115)

Charlottesville, Virginia, 22908, United States

Location

Inova Schar Cancer Institute ( Site 1108)

Fairfax, Virginia, 22031, United States

Location

University Hospital and UW Health Clinics ( Site 1119)

Madison, Wisconsin, 53792, United States

Location

Instituto de Investigaciones Clínicas Mar del Plata ( Site 1213)

Mar del Plata, Buenos Aires, 7600, Argentina

Location

Fundacion Estudios Clinicos-Oncology ( Site 1205)

Rosario, Santa Fe Province, S2000DEJ, Argentina

Location

Sanatorio Finochietto ( Site 1202)

Buenos Aires, C1187AAN, Argentina

Location

Investigaciones Clinicas Moleculares (ICM) ( Site 1212)

CABA, C1425BGH, Argentina

Location

Hospital Italiano de Córdoba ( Site 1204)

Córdoba, X5004BAL, Argentina

Location

Melanoma Institute Australia-Clinical Trials Unit ( Site 3205)

Wollstonecraft, New South Wales, 2065, Australia

Location

Sunshine Coast University Hospital-Medical Oncology ( Site 3212)

Birtinya, Queensland, 4575, Australia

Location

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

Brisbane, Queensland, 4029, Australia

Location

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

Gold Coast, Queensland, 4215, Australia

Location

Gallipoli Medical Research Ltd-GMRF CTU ( Site 3206)

Greenslopes, Queensland, 4120, Australia

Location

Austin Health ( Site 3209)

Heidelberg, Victoria, 3084, Australia

Location

One Clinical Research ( Site 3211)

Nedlands, Western Australia, 6009, Australia

Location

Cliniques universitaires Saint-Luc ( Site 1701)

Brussels, Bruxelles-Capitale, Region de, 1200, Belgium

Location

UZ Gent-Medical oncology ( Site 1702)

Ghent, Oost-Vlaanderen, 9000, Belgium

Location

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

Salvador, Estado de Bahia, 41950-640, Brazil

Location

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

Londrina, Paraná, 86015-520, Brazil

Location

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

Passo Fundo, Rio Grande do Sul, 99010-080, Brazil

Location

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

Porto Alegre, Rio Grande do Sul, 91350-200, Brazil

Location

ANIMI - Unidade de Tratamento Oncologico ( Site 1312)

Lages, Santa Catarina, 88501001, Brazil

Location

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

São José do Rio Preto, São Paulo, 15090-000, Brazil

Location

IPITEC ( Site 1313)

São Paulo, São Paulo, 01223-001, Brazil

Location

Jewish General Hospital ( Site 1009)

Montreal, Quebec, H3T 1E2, Canada

Location

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

Sherbrooke, Quebec, J1H 5H4, Canada

Location

FALP-UIDO ( Site 1401)

Santiago, Region M. de Santiago, 7500921, Chile

Location

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

Santiago, Region M. de Santiago, 7650568, Chile

Location

James Lind Centro de Investigacion del Cancer ( Site 1411)

Temuco, Región de la Araucanía, 4800827, Chile

Location

CIDO SpA-Oncology ( Site 1405)

Temuco, Región de la Araucanía, 4810218, Chile

Location

Fundacion Colombiana de Cancerología Clinica Vida ( Site 1501)

Medellín, Antioquia, 050030, Colombia

Location

Oncologos del Occidente ( Site 1504)

Pereira, Risaralda Department, 660001, Colombia

Location

Fundación Valle del Lili ( Site 1502)

Cali, Valle del Cauca Department, 760032, Colombia

Location

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

Prague, Praha 2, 12808, Czechia

Location

CHU de Bordeaux Hop St ANDRE ( Site 1902)

Bordeaux, Aquitaine, 33075, France

Location

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

Marseille, Bouches-du-Rhone, 13005, France

Location

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

Dijon, Bourgogne-Franche-Comté, 21000, France

Location

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

Toulouse, Haute-Garonne, 31059, France

Location

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

Nantes, Loire-Atlantique, 44093, France

Location

Hopital Claude Huriez - CHU de Lille ( Site 1907)

Lille, Nord, 59037, France

Location

centre hospitalier lyon sud ( Site 1901)

Pierre-Bénite, Rhone, 69310, France

Location

Hôpital Saint-Louis ( Site 1906)

Paris, 75475, France

Location

Gustave Roussy ( Site 1909)

Villejuif, Île-de-France Region, 94800, France

Location

NCT ( Site 2002)

Heidelberg, Baden-Wurttemberg, 69120, Germany

Location

Universitaetsklinikum Tuebingen-Hautklinik ( Site 2003)

Tübingen, Baden-Wurttemberg, 72076, Germany

Location

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

München, Bavaria, 81675, Germany

Location

Universitaetsklinikum Wuerzburg-Department of Dermatology ( Site 2001)

Würzburg, Bavaria, 97080, Germany

Location

Klinikum Dortmund Klinikzentrum Mitte ( Site 2008)

Dortmund, North Rhine-Westphalia, 44137, Germany

Location

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

Essen, North Rhine-Westphalia, 45147, Germany

Location

Universitätsmedizin Johannes Gutenberg Universität Mainz ( Site 2007)

Mainz, Rhineland-Palatinate, 55131, Germany

Location

Universitätsklinikum Schleswig-Holstein-Dermatology ( Site 2012)

Lübeck, Schleswig-Holstein, 23538, Germany

Location

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

Pécs, Baranya, 7632, Hungary

Location

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

Szeged, Csongrád megye, 6720, Hungary

Location

Debreceni Egyetem Klinikai Kozpont-Bőrgyógyászati Klinika ( Site 2102)

Debrecen, 4032, Hungary

Location

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

Győr, 9024, Hungary

Location

Emek Medical Center ( Site 2203)

Afula, 1834111, Israel

Location

Hadassah Medical Center ( Site 2201)

Jerusalem, 9112001, Israel

Location

Rabin Medical Center ( Site 2202)

Petah Tikva, 4941492, Israel

Location

Sheba Medical Center ( Site 2200)

Ramat Gan, 5265601, Israel

Location

Instituto Tumori Giovanni Paolo II ( Site 2301)

Bari, Apulia, 70124, Italy

Location

Ospedale San Martino-Oncologia Medica 2 ( Site 2303)

Genoa, Liguria, 16132, Italy

Location

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

Rozzano, Milano, 20089, Italy

Location

Azienda Ospedaliero Universitaria Senese ( Site 2302)

Siena, Tuscany, 53100, Italy

Location

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

Bergamo, 24127, Italy

Location

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

Naples, 80131, Italy

Location

Harbour Cancer & Wellness ( Site 3300)

Auckland, 1023, New Zealand

Location

Oslo universitetssykehus, Radiumhospitalet ( Site 2400)

Oslo, 0379, Norway

Location

Centrum Medyczne HCP ( Site 2505)

Poznan, Greater Poland Voivodeship, 61-485, Poland

Location

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

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

Location

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

Warsaw, Masovian Voivodeship, 02-781, Poland

Location

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

Gdansk, Pomeranian Voivodeship, 80-952, Poland

Location

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

Kielce, Świętokrzyskie Voivodeship, 25-734, Poland

Location

Spitalul Universitar de Urgență Elias ( Site 2600)

Bucharest, București, 011461, Romania

Location

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

Florești, Cluj, 407280, Romania

Location

Centrul de Oncologie Sfantul Nectarie-Medical ( Site 2601)

Craiova, Dolj, 200542, Romania

Location

Sigmedical Services SRL ( Site 2603)

Suceava, 720214, Romania

Location

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

Badalona, Barcelona, 08916, Spain

Location

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

Barcelona, Catalonia, 08036, Spain

Location

Centro Oncologico de Galicia ( Site 2806)

A Coruña, Galicia, 15009, Spain

Location

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

Madrid, Madrid, Comunidad de, 28034, Spain

Location

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

Málaga, Malaga, 29010, Spain

Location

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

Valencia, Valenciana, Comunitat, 46014, Spain

Location

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

Barcelona, 08035, Spain

Location

Clinica Universidad de Navarra-Medical Oncology ( Site 2807)

Madrid, 28027, Spain

Location

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

Cambridge, Cambridgeshire, CB2 2QQ, United Kingdom

Location

Derriford Hospital-Oncology ( Site 3104)

Plymouth, Devon, Pl6 8DH, United Kingdom

Location

Castle Hill Hospital ( Site 3102)

Cottingham, East Riding Of Yorkshire, HU16 5JQ, United Kingdom

Location

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

Swansea, SA2 8QA, United Kingdom

Location

Related Links

• Merck Clinical Trials Information
• Plain Language Summary

MeSH Terms

Conditions

Carcinoma, Squamous Cell; Skin Neoplasms

Interventions

pembrolizumab; Surgical Procedures, Operative

Condition Hierarchy (Ancestors)

Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Squamous Cell; Neoplasms by Site; Skin Diseases; Skin and Connective Tissue Diseases

Study Officials

• Medical Director

  Merck Sharp & Dohme LLC

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 29, 2024
• First Posted: March 6, 2024
• Study Start: April 18, 2024
• Primary Completion: March 5, 2026
• Study Completion: March 5, 2026
• Last Updated: March 27, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will share

Locations

AU (7); IL (4); NO (1); HU (4); DE (8); CA (2); CO (3); PL (5); NZ (1); CZ (1); AR (5); FR (9); US (21); CL (4); BE (2); RO (4); ES (8); IT (6); BR (7); GB (4)