Clinical trial NCT06295809: A Study of (Neo)Adjuvant Intismeran Autogene (V940) and Pembrolizumab in Cutaneous Squamous Cell Carcinoma (V940-007).
Official title: A Phase 2/3, Adaptive, Randomized, Open-label, Clinical Study to Evaluate Neoadjuvant and Adjuvant Intismeran Autogene (mRNA-4157) in Combination With Pembrolizumab (MK-3475) Versus Standard of Care, and Pembrolizumab Monotherapy in Participants With Resectable Locally Advanced Cutaneous Squamous Cell Carcinoma (LA cSCC) (INTerpath-007).
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
PHASE3
Conditions: Carcinoma, Squamous Cell
Skin Neoplasms
Keywords: pembrolizumab
Lead sponsor: Merck Sharp & Dohme LLC
Sponsor class: INDUSTRY
Collaborators: name: ModernaTX, Inc.
First posted: 2024-03-06
Enrollment: 1012
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: In the Phase 2 of the study design, approximately 600 participants will be randomly assigned into 3 arms in an approximate 5:5:2 ratio (250 to intismeran autogene plus pembrolizumab with SOC, 250 participants to SOC only, and 100 participants to pembrolizumab monotherapy with SOC). If the decision is made to expand the study to Phase 3, the 600 participants enrolled in Phase 2 will keep their originally assigned study intervention arms in the Phase 3 Expansion, and 412 new participants will be enrolled and randomly assigned in a 1:1 ratio to receive treatment with either intismeran autogene plus pembrolizumab with SOC or SOC only. New participants will not be randomized into the pembrolizumab monotherapy with SOC arm during the Phase 3 Expansion.
Primary purpose: TREATMENT

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.


Eligibility criteria: 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
* Has a 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
* Has a history of allogeneic tissue/solid organ transplant
* Has not adequately recovered from major surgery or have ongoing surgical complications

Primary outcomes:
measure: Event Free Survival (EFS)
timeFrame: Up to ~59 months
Secondary outcomes:
measure: Overall response rate (ORR)
timeFrame: Up to ~38 months
measure: Freedom from surgery (FFS) rate
timeFrame: Up to ~38 months
measure: Pathological complete response (pCR) rate
timeFrame: Up to ~38 months
measure: Major pathological response (mPR) rate
timeFrame: Up to ~38 months
measure: Disease-free survival (DFS)
timeFrame: Up to ~59 months
measure: Disease-specific survival (DSS)
timeFrame: Up to ~59 months
measure: Overall Survival (OS)
timeFrame: Up to ~59 months
measure: Percentage of participants who experience and adverse event (AE)
timeFrame: Up to ~59 months
measure: Percentage of participants who discontinue study intervention due to AEs
timeFrame: Up to ~19 months
measure: Change from baseline in Global health status/QoL score (QLQ-C30 Items 29 and 30)
timeFrame: Baseline and up to ~38 months
measure: Change from baseline in physical functioning score of QLQ (C30 Items 1-5)
timeFrame: Baseline and up to ~38 months
measure: Change from baseline in Role functioning score of QLQ-C30 Items 6-7
timeFrame: Baseline and up to ~38 months
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: USC/Norris Comprehensive Cancer Center ( Site 1112)
state: California
city: Newport Beach
country: United States
facility: Hoag Memorial Hospital Presbyterian ( Site 1122)
state: California
city: Palo Alto
country: United States
facility: Stanford Cancer Center ( Site 1109)
state: California
city: Sacramento
country: United States
facility: University of California Davis (UC Davis) Comprehensive Cancer Center ( Site 1103)
state: California
city: Atlanta
country: United States
facility: Winship Cancer Institute, Emory University ( Site 1151)
state: Georgia
city: Iowa City
country: United States
facility: University of Iowa-Holden Comprehensive Cancer Center ( Site 1118)
state: Iowa
city: Lexington
country: United States
facility: University of Kentucky Chandler Medical Center ( Site 1101)
state: Kentucky
city: New Orleans
country: United States
facility: Ochsner Clinic Foundation ( Site 1113)
state: Louisiana
city: Boston
country: United States
facility: Massachusetts General Hospital ( Site 1162)
state: Massachusetts
city: Boston
country: United States
facility: Dana-Farber Cancer Institute ( Site 1130)
state: Massachusetts
city: Saint Louis
country: United States
facility: Washington University School of Medicine-Internal Medicine/Oncology ( Site 1100)
state: Missouri
city: Hackensack
country: United States
facility: John Theurer Cancer Center at Hackensack University Medical Center ( Site 1125)
state: New Jersey
city: Morristown
country: United States
facility: Atlantic Health System Morristown Medical Center ( Site 1136)
state: New Jersey
city: Mineola
country: United States
facility: Perlmutter Cancer Center at NYU Langone Hospital - Long Island ( Site 1160)
state: New York
city: New York
country: United States
facility: Laura and Isaac Perlmutter Cancer Center ( Site 1121)
state: New York
city: Portland
country: United States
facility: Providence Portland Medical Center ( Site 1102)
state: Oregon
city: Pittsburgh
country: United States
facility: UPMC Hillman Cancer Center ( Site 1107)
state: Pennsylvania
city: Sioux Falls
country: United States
facility: Avera Cancer Institute- Research ( Site 1161)
state: South Dakota
city: Charlottesville
country: United States
facility: University of Virginia Health System ( Site 1115)
state: Virginia
city: Fairfax
country: United States
facility: Inova Schar Cancer Institute ( Site 1108)
state: Virginia
city: Madison
country: United States
facility: University Hospital and UW Health Clinics ( Site 1119)
state: Wisconsin
city: Mar del Plata
country: Argentina
facility: Instituto de Investigaciones Clínicas Mar del Plata ( Site 1213)
state: Buenos Aires
city: Rosario
country: Argentina
facility: Fundacion Estudios Clinicos-Oncology ( Site 1205)
state: Santa Fe
city: Buenos Aires
country: Argentina
facility: Sanatorio Finochietto ( Site 1202)
city: Caba
country: Argentina
facility: Investigaciones Clinicas Moleculares (ICM) ( Site 1212)
city: Cordoba
country: Argentina
facility: Hospital Italiano de Córdoba ( Site 1204)
city: Wollstonecraft
country: Australia
facility: Melanoma Institute Australia-Clinical Trials Unit ( Site 3205)
state: New South Wales
city: Birtinya
country: Australia
facility: Sunshine Coast University Hospital-Medical Oncology ( Site 3212)
state: Queensland
city: Brisbane
country: Australia
facility: Royal Brisbane and Women's Hospital-Medical Oncology Clinical Trials Unit, Cancer Care Services ( Si
state: Queensland
city: Gold Coast
country: Australia
facility: Gold Coast University Hospital-Cancer and Blood Disorders Clinical Trial Team ( Site 3207)
state: Queensland
city: Greenslopes
country: Australia
facility: Gallipoli Medical Research Ltd-GMRF CTU ( Site 3206)
state: Queensland
city: Heidelberg
country: Australia
facility: Austin Health ( Site 3209)
state: Victoria
city: Nedlands
country: Australia
facility: One Clinical Research ( Site 3211)
state: Western Australia
city: Brussels
country: Belgium
facility: Cliniques universitaires Saint-Luc ( Site 1701)
state: Bruxelles-Capitale, Region De
city: Gent
country: Belgium
facility: UZ Gent-Medical oncology ( Site 1702)
state: Oost-Vlaanderen
city: Salvador
country: Brazil
facility: Clinica Amo - Rio Vermelho-INSTITUTO ETICA ( Site 1315)
state: Bahia
city: Londrina
country: Brazil
facility: Hospital de Cancer de Londrina-Clinical Research Unit ( Site 1316)
state: Parana
city: Passo Fundo
country: Brazil
facility: Associação Hospitalar Beneficente São Vicente de Paulo-Instituto do Câncer ( Site 1309)
state: Rio Grande Do Sul
city: Porto Alegre
country: Brazil
facility: Hospital Nossa Senhora da Conceição-Centro Integrado de Pesquisa em Oncologia ( Site 1300)
state: Rio Grande Do Sul
city: Lages
country: Brazil
facility: ANIMI - Unidade de Tratamento Oncologico ( Site 1312)
state: Santa Catarina
city: São José do Rio Preto
country: Brazil
facility: Fundação Faculdade Regional de Medicina de São José do Rio Preto-Centro Integrado de Pesquisa ( Site
state: Sao Paulo
city: São Paulo
country: Brazil
facility: IPITEC ( Site 1313)
state: Sao Paulo
city: Montreal
country: Canada
facility: Jewish General Hospital ( Site 1009)
state: Quebec
city: Sherbrooke
country: Canada
facility: Centre intégré universitaire de santé et de services sociaux de l'Estrie - Centre Hospitalier Univer
state: Quebec
city: Temuco
country: Chile
facility: James Lind Centro de Investigacion del Cancer ( Site 1411)
state: Araucania
city: Temuco
country: Chile
facility: CIDO SpA-Oncology ( Site 1405)
state: Araucania
city: Santiago
country: Chile
facility: FALP-UIDO ( Site 1401)
state: Region M. De Santiago
city: Santiago
country: Chile
facility: Clínica Alemana de Santiago-Gynecology and Obstetrics ( Site 1410)
state: Region M. De Santiago
city: Medellín
country: Colombia
facility: Fundacion Colombiana de Cancerología Clinica Vida ( Site 1501)
state: Antioquia
city: Pereira
country: Colombia
facility: Oncologos del Occidente ( Site 1504)
state: Risaralda
city: Cali
country: Colombia
facility: Fundación Valle del Lili ( Site 1502)
state: Valle Del Cauca
city: Prague
country: Czechia
facility: Vseobecna fakultni nemocnice v Praze-Department of Dermatology ( Site 1800)
state: Praha 2
city: Bordeaux
country: France
facility: CHU de Bordeaux Hop St ANDRE ( Site 1902)
state: Aquitaine
city: Marseille
country: France
facility: Assistance Publique Hôpitaux de Marseille - Hôpital de la Timone ( Site 1903)
state: Bouches-du-Rhone
city: Dijon
country: France
facility: Centre Hospitalier Universitaire Dijon Bourgogne - Hôpital François Mitterrand ( Site 1904)
state: Bourgogne
city: Toulouse
country: France
facility: Institut Universitaire du Cancer Toulouse - Oncopole - CHU de TOULOUSE ( Site 1908)
state: Haute-Garonne
city: Villejuif
country: France
facility: Gustave Roussy ( Site 1909)
state: Ile-de-France
city: Nantes
country: France
facility: Centre Hospitalier Universitaire de Nantes - L' Hopital l'hôtel-Dieu-Onco-Dermatology ( Site 1910)
state: Loire-Atlantique
city: Lille
country: France
facility: Hopital Claude Huriez - CHU de Lille ( Site 1907)
state: Nord
city: Pierre-Bénite
country: France
facility: centre hospitalier lyon sud ( Site 1901)
state: Rhone
city: Paris
country: France
facility: Hôpital Saint-Louis ( Site 1906)
city: Heidelberg
country: Germany
facility: NCT ( Site 2002)
state: Baden-Wurttemberg
city: Tübingen
country: Germany
facility: Universitaetsklinikum Tuebingen-Hautklinik ( Site 2003)
state: Baden-Wurttemberg
city: München
country: Germany
facility: klinikum rechts der isar der technischen universität münchen ( Site 2009)
state: Bayern
city: Wuerzburg
country: Germany
facility: Universitaetsklinikum Wuerzburg-Department of Dermatology ( Site 2001)
state: Bayern
city: Dortmund
country: Germany
facility: Klinikum Dortmund Klinikzentrum Mitte ( Site 2008)
state: Nordrhein-Westfalen
city: Essen
country: Germany
facility: Universitaetsklinikum Essen-Klinik für Dermatologie, Venerologie und Allergologie ( Site 2005)
state: Nordrhein-Westfalen
city: Mainz
country: Germany
facility: Universitätsmedizin Johannes Gutenberg Universität Mainz ( Site 2007)
state: Rheinland-Pfalz
city: Lubeck
country: Germany
facility: Universitätsklinikum Schleswig-Holstein-Dermatology ( Site 2012)
state: Schleswig-Holstein
city: Pecs
country: Hungary
facility: Pécsi Tudományegyetem Klinikai Központ-Bőr-, Nemikórtani és Onkodermatológiai Klinika ( Site 2100)
state: Baranya
city: Szeged
country: Hungary
facility: Szegedi Tudományegyetem Szent-Györgyi Albert Klinikai Közpo-Department of Dermatology and Allergol
state: Csongrad
city: Debrecen
country: Hungary
facility: Debreceni Egyetem Klinikai Kozpont-Bőrgyógyászati Klinika ( Site 2102)
city: Gyor
country: Hungary
facility: Gyor-Moson-Sopron Varmegyei Petz Aladar Egyetemi Oktato Korhaz- Onkoradiologiai Osztaly ( Site 2110)
city: Afula
country: Israel
facility: Emek Medical Center ( Site 2203)
city: Jerusalem
country: Israel
facility: Hadassah Medical Center ( Site 2201)
city: Petah Tikva
country: Israel
facility: Rabin Medical Center ( Site 2202)
city: Ramat Gan
country: Israel
facility: Sheba Medical Center ( Site 2200)
city: Genova
country: Italy
facility: Ospedale San Martino-Oncologia Medica 2 ( Site 2303)
state: Liguria
city: Rozzano
country: Italy
facility: Istituto Clinico Humanitas-U.O di Oncologia medica ed Ematologia ( Site 2304)
state: Milano
city: Bari
country: Italy
facility: Instituto Tumori Giovanni Paolo II ( Site 2301)
state: Puglia
city: Siena
country: Italy
facility: Azienda Ospedaliero Universitaria Senese ( Site 2302)
state: Toscana
city: Bergamo
country: Italy
facility: Azienda Socio Sanitaria Territoriale Papa Giovanni XXIII-UOC Oncologia ( Site 2305)
city: Napoli
country: Italy
facility: Istituto Nazionale Tumori IRCCS Fondazione Pascale-s.c. melanoma, immunoterapia oncologica e terapi
city: Auckland
country: New Zealand
facility: Harbour Cancer & Wellness ( Site 3300)
city: Oslo
country: Norway
facility: Oslo universitetssykehus, Radiumhospitalet ( Site 2400)
city: Bydgoszcz
country: Poland
facility: Centrum Onkologii im. Prof. Franciszka Lukaszczyka-Ambulatorium Chemioterapii ( Site 2501)
state: Kujawsko-pomorskie
city: Warszawa
country: Poland
facility: Narodowy Instytut Onkologii im. Marii Sklodowskiej-Curie - Panstwowy Instytut Badawczy w Warszawie (
state: Mazowieckie
city: Gdansk
country: Poland
facility: Uniwersyteckie Centrum Kliniczne-Early Clinical Trials Unit ( Site 2506)
state: Pomorskie
city: Kielce
country: Poland
facility: Swietokrzyskie Centrum Onkologii, Samodzielny Publiczny Zakl-Klinika Onkologii Klinicznej, Dzial Ch
state: Swietokrzyskie
city: Poznań
country: Poland
facility: Centrum Medyczne HCP ( Site 2505)
state: Wielkopolskie
city: București
country: Romania
facility: Spitalul Universitar de Urgență Elias ( Site 2600)
state: Bucuresti
city: Florești
country: Romania
facility: SC Radiotherapy Center Cluj SRL-Oncologie Medicala ( Site 2602)
state: Cluj
city: Craiova
country: Romania
facility: Centrul de Oncologie Sfantul Nectarie-Medical ( Site 2601)
state: Dolj
city: Suceava
country: Romania
facility: Sigmedical Services SRL ( Site 2603)
city: Badalona
country: Spain
facility: Hospital Germans Trias i Pujol-Instituto Catalán de Oncología de Badalona ( Site 2804)
state: Barcelona
city: Barcelona
country: Spain
facility: HOSPITAL CLÍNIC DE BARCELONA-ICHMO- Clinic Institut of Haematological and Oncological diseases ( Sit
state: Cataluna
city: A Coruna
country: Spain
facility: Centro Oncologico de Galicia ( Site 2806)
state: Galicia
city: Madrid
country: Spain
facility: Hospital Universitario Ramón y Cajal-Medical Oncology ( Site 2801)
state: Madrid, Comunidad De
city: Málaga
country: Spain
facility: H.R.U Malaga - Hospital General ( Site 2805)
state: Malaga
city: Valencia
country: Spain
facility: Hospital General Universitario de Valencia-oncology service ( Site 2802)
state: Valenciana, Comunitat
city: Barcelona
country: Spain
facility: Hospital Universitari Vall d'Hebron-Departamento de Oncologia- VHIO ( Site 2803)
city: Madrid
country: Spain
facility: Clinica Universidad de Navarra-Medical Oncology ( Site 2807)
city: Cambridge
country: United Kingdom
facility: Addenbrooke's Hospital-Cambridge Cancer Trials Centre ( Site 3103)
state: Cambridgeshire
city: Plymouth
country: United Kingdom
facility: Derriford Hospital-Oncology ( Site 3104)
state: Devon
city: Cottingham
country: United Kingdom
facility: Castle Hill Hospital ( Site 3102)
state: East Riding Of Yorkshire
city: Swansea
country: United Kingdom
facility: Singleton Hospital-South West Wales Cancer Institute ( Site 3100)
Study officials:
affiliation: Merck Sharp & Dohme LLC
name: Medical Director
role: STUDY_DIRECTOR
References: