Clinical trial • Phase II/III • Oncology
MRNA-4157 for Non-small cell lung cancer (stage IV) | Squamous non-small cell lung cancer
Phase II/III trial of MRNA-4157 for Non-small cell lung cancer (stage IV) | Squamous non-small cell lung cancer.
Overview
- Trial Therapeutic Area
- Oncology
- Trial Disease
- Non-small cell lung cancer (stage IV) | Squamous non-small cell lung cancer
- Trial Stage
- Phase II/III
- Drug Modality
- mRNA | Monoclonal antibody | Small molecule
Key dates
- Initial CTIS Submission Date
- 09-10-2025
- First CTIS Authorization Date
- 23-03-2026
Trial design
Randomised, placebo to v940 (placebo) combined with pembrolizumab and platinum-based chemotherapy (background regimen includes carboplatin and taxane agents such as paclitaxel/paclitaxel albumin-bound or docetaxel) — placebo arm compared versus v940 arm; specific v940 dose/schedule not provided in ctis data.-controlled Phase II/III trial in France, Italy, Spain and others.
- Randomised
- Yes
- Comparator
- Placebo to V940 (Placebo) combined with pembrolizumab and platinum-based chemotherapy (background regimen includes carboplatin and taxane agents such as paclitaxel/paclitaxel albumin-bound or docetaxel) — placebo arm compared versus V940 arm; specific V940 dose/schedule not provided in CTIS data.
- Target Sample Size
- 123
Eligibility
Recruits 123 No vulnerable population selected in the application. Participants must be ≥18 years at the time of providing informed consent. No assent or minor consent procedures are described in the available CTIS data..
- Vulnerable Population
- No vulnerable population selected in the application. Participants must be ≥18 years at the time of providing informed consent. No assent or minor consent procedures are described in the available CTIS data.
Inclusion criteria
- {"criterion_text":"- The participant must have a histologically or cytologically confirmed diagnosis of squamous non-small cell lung cancer (NSCLC) (Stage IV: M1a, M1b, M1c1, M1c2, American Joint Committee on Cancer (AJCC) Staging Manual, Version 9). NOTE: Mixed tumors will be characterized by the predominant cell type; however, small cell elements are not permitted.\n- Has a life expectancy of at least 3 months\n- Has adequate organ function\n- Is of any sex/gender, from 18 years at the time of providing the informed consent.\n- Has measurable disease per RECIST 1.1 as assessed by the local site investigator/radiology\n- Has provided a tissue sample that is collected either at the time of or after the diagnosis of metastatic disease AND is from a site not previously irradiated\n- Have AEs due to previous anticancer therapies must have recovered to ≤Grade 1. Participants with endocrine-related AEs who are adequately treated with hormone replacement or participants who have ≤Grade 2 neuropathy are eligible\n- Human immunodeficiency virus (HIV)-infected participants must have well controlled HIV on antiretroviral therapy (ART)\n- Hepatitis B surface antigen (HBsAg) positive participants are eligible if they have received hepatitis B virus (HBV) antiviral therapy for at least 4 weeks, and have undetectable HBV viral load prior to randomization\n- Participants with history of hepatitis C virus (HCV) infection are eligible if HCV viral load is undetectable. NOTE: Participants must have completed curative antiviral therapy at least 4 weeks prior to randomization\n- Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1 assessed within 7 days before randomization"}
Exclusion criteria
- {"criterion_text":"- Is a HIV-infected participant with a history of Kaposi’s sarcoma and/or Multicentric Castleman’s Disease\n- Has known additional malignancy that is progressing or has required active treatment within the past 3 years\n- Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis\n- Has severe hypersensitivity (≥Grade 3) to V940, pembrolizumab, or any of the protocol allowed chemotherapy agents and/or any of their excipients\n- Has active autoimmune disease that has required systemic treatment in the past 2 years\n- Has a history of (noninfectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease\n- Has active infection requiring systemic therapy\n- Has a history of stem cell/solid organ transplant\n- Has not adequately recovered from major surgery or have ongoing surgical complications\n- Has received prior treatment with a cancer vaccine, including another personalized cancer vaccine (PCV)\n- Has received prior systemic anticancer therapy for their metastatic NSCLC\n- Has received prior therapy with an anti-programmed cell death 1 protein (PD-1), anti-programmed cell death ligand 1 (PD-L1), or anti-programmed cell death ligand 2 (PD-L2) agent, or with an agent directed to another stimulatory or coinhibitory T-cell receptor. NOTE: Prior treatment with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent in the neoadjuvant or adjuvant setting for nonmetastatic NSCLC is allowed as long as therapy was completed at least 12 months before diagnosis of metastatic NSCLC\n- Has received prior radiotherapy within 2 weeks of start of study intervention, or has radiation-related toxicities, requiring corticosteroids\n- Has received radiation therapy to the lung that is >30 gray within 6 months of start of study intervention\n- Has received a live or live-attenuated vaccine within 30 days before the first dose of study intervention. Administration of killed vaccines is allowed\n- Has received an investigational agent or has used an investigational device within 4 weeks prior to study intervention administration\n- 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 to the first dose of study intervention"}
Endpoints
Primary endpoints
- {"endpoint_text":"- Progression-free survival (PFS)","definition_or_measurement_approach":"Progression-free survival (PFS) as per Response Evaluation Criteria In Solid Tumors (RECIST) 1.1, as assessed by blinded independent central review (BICR)"}
- {"endpoint_text":"- Overall survival (OS)","definition_or_measurement_approach":"Overall survival (OS); all-cause mortality measured from randomisation (no additional measurement detail provided)"}
Secondary endpoints
- {"endpoint_text":"- Objective response rate (ORR)","definition_or_measurement_approach":"Objective response rate (ORR) as per RECIST 1.1, as assessed by blinded independent central review (BICR)"}
- {"endpoint_text":"- Duration of response (DOR)","definition_or_measurement_approach":"Duration of response (DOR) as per RECIST 1.1, as assessed by blinded independent central review (BICR)"}
- {"endpoint_text":"- Number of Participants With ≥1 Adverse Event (AE)","definition_or_measurement_approach":"Count of participants experiencing ≥1 adverse event (AE) (safety/tolerability measure)"}
- {"endpoint_text":"- Number of Participants Discontinuing From Study Therapy Due to an AE","definition_or_measurement_approach":"Count of participants who discontinue study therapy because of an adverse event"}
Recruitment
- Planned Sample Size
- 123
- Recruitment Window Months
- 64
- Consent Approach
- Informed consent obtained from each participant; participants must be ≥18 years at the time of providing informed consent. Country-specific informed consent forms and documentation are present for France, Italy, Spain and Poland in the CTIS documents (subject information and ICF documents listed). No assent/minor consent procedures described.
Geography
- Total Number Of Sites
- 19
- Total Number Of Participants
- 59
France
- Earliest CTIS Part Ii Submission Date
- 09-12-2025
- Latest Decision Or Authorization Date
- 30-03-2026
- Processing Time Days
- 111
- Number Of Sites
- 3
- Number Of Participants
- 10
Sites
- Site Name
- University Hospital Of Clermont-Ferrand
- Department Name
- Oncology
- Principal Investigator Name
- Henri JANICOT
- Principal Investigator Email
- hjanicot@chu-clermontferrand.fr
- Contact Person Name
- Henri JANICOT
- Contact Person Email
- hjanicot@chu-clermontferrand.fr
- Site Name
- Centr Georges Francois Leclerc
- Department Name
- Oncology
- Principal Investigator Name
- Courèche Guillaume KADERBHAI
- Principal Investigator Email
- cgkaderbhai@cgfl.fr
- Contact Person Name
- Courèche Guillaume KADERBHAI
- Contact Person Email
- cgkaderbhai@cgfl.fr
- Site Name
- Institut De Cancerologie De L Ouest
- Department Name
- Oncology
- Principal Investigator Name
- Pierre BIGOT
- Principal Investigator Email
- Frederic.bigot@ico.unicancer.fr
- Contact Person Name
- Pierre BIGOT
- Contact Person Email
- Frederic.bigot@ico.unicancer.fr
Italy
- Earliest CTIS Part Ii Submission Date
- 23-01-2026
- Latest Decision Or Authorization Date
- 23-03-2026
- Processing Time Days
- 59
- Number Of Sites
- 5
- Number Of Participants
- 15
Sites
- Site Name
- Azienda Unita Sanitaria Locale Della Romagna
- Department Name
- Dipartimento Oncoematologico
- Principal Investigator Name
- Chaira Bennati
- Principal Investigator Email
- chiara.bennati@auslromagna.it
- Contact Person Name
- Chaira Bennati
- Contact Person Email
- chiara.bennati@auslromagna.it
- Site Name
- Istituto Europeo Di Oncologia S.r.l.
- Department Name
- Divisione di Oncologia Toracica Divisione Sviluppo di Nuovi Farmaci per Terapie Innovative
- Principal Investigator Name
- Filippo De Marinis
- Principal Investigator Email
- filippo.demarinis@ieo.it
- Contact Person Name
- Filippo De Marinis
- Contact Person Email
- filippo.demarinis@ieo.it
- Site Name
- Fondazione Policlinico Universitario Agostino Gemelli IRCCS
- Department Name
- UOC Oncologia Medica
- Principal Investigator Name
- Emilio Bria
- Principal Investigator Email
- emilio.bria@policlinicogemelli.it
- Contact Person Name
- Emilio Bria
- Contact Person Email
- emilio.bria@policlinicogemelli.it
- Site Name
- Ospedale San Raffaele S.r.l.
- Department Name
- Oncologia Medica
- Principal Investigator Name
- Roberto Ferrara
- Principal Investigator Email
- ferrara.roberto@hsr.it
- Contact Person Name
- Roberto Ferrara
- Contact Person Email
- ferrara.roberto@hsr.it
- Site Name
- Fondazione IRCCS Istituto Nazionale Dei Tumori
- Department Name
- Struttura Complessa Oncologica
- Principal Investigator Name
- Marta Brambilla
- Principal Investigator Email
- marta.brambilla2@istitutotumori.mi.it
- Contact Person Name
- Marta Brambilla
- Contact Person Email
- marta.brambilla2@istitutotumori.mi.it
Spain
- Earliest CTIS Part Ii Submission Date
- 22-01-2026
- Latest Decision Or Authorization Date
- 27-03-2026
- Processing Time Days
- 64
- Number Of Sites
- 6
- Number Of Participants
- 22
Sites
- Site Name
- Hospital Universitario Ramon Y Cajal
- Department Name
- Medical Oncology
- Principal Investigator Name
- Pilar Garrido López
- Principal Investigator Email
- pgarrido@salud.madrid.org
- Contact Person Name
- Pilar Garrido López
- Contact Person Email
- pgarrido@salud.madrid.org
- Site Name
- Hospital Universitario Virgen De La Macarena
- Department Name
- Oncology
- Principal Investigator Name
- David Vicente Baz
- Principal Investigator Email
- david.vbaz@gmail.com
- Contact Person Name
- David Vicente Baz
- Contact Person Email
- david.vbaz@gmail.com
- Site Name
- Institut Catala D'oncologia
- Department Name
- Medical Oncology
- Principal Investigator Name
- Ernest Nadal Alforja
- Principal Investigator Email
- contactfortrialsICOLH@iconcologia.net
- Contact Person Name
- Ernest Nadal Alforja
- Contact Person Email
- contactfortrialsICOLH@iconcologia.net
- Site Name
- Hospital Universitari Vall D Hebron
- Department Name
- Oncology
- Principal Investigator Name
- Enriqueta Felip Font
- Principal Investigator Email
- efelip@vhio.net
- Contact Person Name
- Enriqueta Felip Font
- Contact Person Email
- efelip@vhio.net
- Site Name
- Hospital De Jerez De La Frontera
- Department Name
- Oncology
- Principal Investigator Name
- Jesús Corral Jaime
- Principal Investigator Email
- jesus.corral.jaime.sspa@juntadeandalucia.es
- Contact Person Name
- Jesús Corral Jaime
- Contact Person Email
- jesus.corral.jaime.sspa@juntadeandalucia.es
- Site Name
- Hospital Clinico San Carlos
- Department Name
- Medical Oncology
- Principal Investigator Name
- Carlos Aguado de la Rosa
- Principal Investigator Email
- carlos.aguadodela@salud.madrid.org
- Contact Person Name
- Carlos Aguado de la Rosa
- Contact Person Email
- carlos.aguadodela@salud.madrid.org
Poland
- Earliest CTIS Part Ii Submission Date
- 14-01-2026
- Latest Decision Or Authorization Date
- 27-03-2026
- Processing Time Days
- 72
- Number Of Sites
- 5
- Number Of Participants
- 12
Sites
- Site Name
- Wielkopolskie Centrum Pulmonologii I Torakochirurgii Im. Eugenii I Janusza Zeylandow
- Department Name
- Odział Onkologii Klinicznej z Pododdziałem Dziennej Chemioterapii
- Principal Investigator Name
- Katarzyna Stencel
- Principal Investigator Email
- kstencel@wcpit.org
- Contact Person Name
- Katarzyna Stencel
- Contact Person Email
- kstencel@wcpit.org
- Site Name
- Uniwersyteckie Centrum Kliniczne
- Department Name
- Ośrodek Badań Klinicznych Wczesnych Faz
- Principal Investigator Name
- Natalia Cichowska-Cwalińska
- Principal Investigator Email
- obkwf@uck.gda.pl
- Contact Person Name
- Natalia Cichowska-Cwalińska
- Contact Person Email
- obkwf@uck.gda.pl
- Site Name
- Szpital Wojewodzki Im. Mikolaja Kopernika W Koszalinie
- Department Name
- Oddział Onkologii Klinicznej z Pododdziałem Chemioterapii Jednodniowej
- Principal Investigator Name
- Mariusz Kwiatkowski
- Principal Investigator Email
- sekretariat.odch@swk.med.pl
- Contact Person Name
- Mariusz Kwiatkowski
- Contact Person Email
- sekretariat.odch@swk.med.pl
- Site Name
- Narodowy Instytut Onkologii Im. Marii Sklodowskiej-Curie Panstwowy Instytut Badawczy
- Department Name
- Klinika Nowotworów Płuca i Klatki Piersiowej
- Principal Investigator Name
- Dariusz Kowalski
- Principal Investigator Email
- paulina.kukwa@nio.gov.pl
- Contact Person Name
- Dariusz Kowalski
- Contact Person Email
- paulina.kukwa@nio.gov.pl
- Site Name
- Wojewodzki Szpital Im. Sw.Ojca Pio W Przemyslu
- Department Name
- Oddział Onkologiczny z Pododdziałem Dziennej Chemioterapii
- Principal Investigator Name
- Kamil Kuć
- Principal Investigator Email
- kkuc@wszp.pl
- Contact Person Name
- Kamil Kuć
- Contact Person Email
- kkuc@wszp.pl
Sponsor
Primary sponsor
- Full Name
- Merck Sharp & Dohme LLC
- Organisation Type
- Pharmaceutical company
- Country Of Registered Address
- United States
Contract research organisations
- Name
- Parexel International Corp.
- Responsibilities
- EUB services (call center and medical services); sponsorDuties code 15
- Name
- Pharmaceutical Product Development LLC (PPD)
- Responsibilities
- sponsorDuties code 4
- Name
- Charles River Laboratories International Inc.
- Responsibilities
- sponsorDuties code 4
- Name
- Almac Clinical Technologies LLC
- Responsibilities
- sponsorDuties code 3
- Name
- Fortrea Inc.
- Responsibilities
- sponsorDuties code 1
- Name
- Bioclinica Inc.
- Responsibilities
- sponsorDuties code 7
Third parties
- {"country":"United States","full_name":"Reify Health Inc.","duties_or_roles":"sponsorDuties codes: 2","organisation_type":"Hospital/Clinic/Other health care facility"}
- {"country":"United States","full_name":"Personalis Inc.","duties_or_roles":"sponsorDuties codes: 4","organisation_type":"Laboratory/Research/Testing facility"}
- {"country":"United States","full_name":"Charles River Laboratories International Inc.","duties_or_roles":"sponsorDuties codes: 4","organisation_type":"Pharmaceutical company"}
- {"country":"United States","full_name":"Greenphire LLC","duties_or_roles":"sponsorDuties codes: 2","organisation_type":"Non-Pharmaceutical company"}
- {"country":"United States","full_name":"Parexel International Corp.","duties_or_roles":"sponsorDuties codes: 15; value: EUB services (call center and medical services)","organisation_type":"Pharmaceutical company"}
- {"country":"United States","full_name":"Hematogenix Laboratory Services LLC","duties_or_roles":"sponsorDuties codes: 4","organisation_type":"Laboratory/Research/Testing facility"}
- {"country":"United States","full_name":"Pharmaceutical Product Development LLC","duties_or_roles":"sponsorDuties codes: 4","organisation_type":"Pharmaceutical company"}
- {"country":"United States","full_name":"Infinity Biologix LLC","duties_or_roles":"sponsorDuties codes: 4","organisation_type":"Pharmaceutical company"}
- {"country":"United States","full_name":"Bioclinica Inc.","duties_or_roles":"sponsorDuties codes: 7","organisation_type":"Laboratory/Research/Testing facility"}
- {"country":"Belgium","full_name":"PPD Global Central Labs","duties_or_roles":"sponsorDuties codes: 4","organisation_type":"Pharmaceutical company"}
- {"country":"United States","full_name":"Fortrea Inc.","duties_or_roles":"sponsorDuties codes: 1","organisation_type":"Pharmaceutical company"}
- {"country":"United States","full_name":"Almac Clinical Technologies LLC","duties_or_roles":"sponsorDuties codes: 3","organisation_type":"Pharmaceutical company"}
- {"country":"United States","full_name":"Medidata Solutions Inc.","duties_or_roles":"sponsorDuties codes: 7","organisation_type":"Non-Pharmaceutical company"}
Investigational products
- Investigational Product Name
- mRNA-4157
- Active Substance
- MRNA-4157
- Modality
- mRNA
- Routes Of Administration
- INTRAMUSCULAR USE
- Route
- INTRAMUSCULAR USE
- Maximum Dose
- max daily 1 mg; max total 9 mg
- Investigational Product Name
- KEYTRUDA 25 mg/mL concentrate for solution for infusion.
- Active Substance
- PEMBROLIZUMAB
- Modality
- Monoclonal antibody
- Routes Of Administration
- INTRAVENOUS INFUSION
- Route
- INTRAVENOUS INFUSION
- Authorisation Status
- EU marketing authorisation EU/1/15/1024/002
- Maximum Dose
- max daily 400 mg; max total 6800 mg
- Investigational Product Name
- PACLITAXEL ALBUMIN-BOUND
- Active Substance
- PACLITAXEL ALBUMIN-BOUND
- Modality
- Small molecule
- Routes Of Administration
- INTRAVENOUS INFUSION
- Route
- INTRAVENOUS INFUSION
- Maximum Dose
- max daily 100 mg/m2; max total 1200 mg
- Investigational Product Name
- PACLITAXEL
- Active Substance
- PACLITAXEL
- Modality
- Small molecule
- Routes Of Administration
- INTRAVENOUS INFUSION
- Route
- INTRAVENOUS INFUSION
- Maximum Dose
- max daily 200 mg/m2; max total 800 mg/m2
- Investigational Product Name
- DOCETAXEL
- Active Substance
- DOCETAXEL
- Modality
- Small molecule
- Routes Of Administration
- INTRAVENOUS INFUSION
- Route
- INTRAVENOUS INFUSION
- Maximum Dose
- max daily 75 mg/m2; max total 225 mg
- Investigational Product Name
- CARBOPLATIN
- Active Substance
- CARBOPLATIN
- Modality
- Small molecule
- Routes Of Administration
- INTRAVENOUS INFUSION
- Route
- INTRAVENOUS INFUSION
- Maximum Dose
- max daily 900 mg; max total 3600 mg
- Investigational Product Name
- Placebo to V940
- Modality
- Other
- Combination Treatment
- Yes
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