A Study of Intismeran Autogene (V940)/Placebo + Pembrolizumab and Chemotherapy in Metastatic Squamous Non-Small Cell Lung Cancer (V940-013)

NCT07221474 | Recruiting Phase 2 FDA Drug

• 3 other identifiers: V940-013U1111-1318-24952025-520902-37-00
• Study Type: interventional
• Target: 180
• Locations: 11 countries
• Sites: 51

Brief Summary

Researchers want to know if intismeran autogene (the study treatment) given with pembrolizumab and chemotherapy can treat metastatic treatment-naive squamous non-small cell lung cancer (NSCLC). Intismeran autogene is designed to help a person's immune system attack their specific cancer. The goal of this study is to learn if people who receive intismeran autogene with pembrolizumab and chemotherapy live longer overall and without the cancer growing or spreading compared to people who receive placebo with pembrolizumab and chemotherapy. A placebo looks like the study treatment but has no study treatment in it. Using a placebo helps researchers better understand the effects of the study treatment.

Conditions

Squamous Non-small Cell Lung Cancer

Outcome Measures

Primary Outcomes (2)

• Progression Free Survival (PFS)

  PFS is defined as the time from randomization to the first documented progressive disease (PD) or death due to any cause, whichever occurs first as assessed by Response Criteria in Solid Tumors Version 1.1 (RECIST 1.1). PD is defined as ≥20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of ≥5 mm. The appearance of one or more new lesions is also considered PD. PFS as assessed by blinded independent central review (BICR) will be presented.

  Up to ~32 months

• Overall Survival (OS)

  OS, defined as the time from randomization to death due to any cause. OS will be presented.

  Up to ~42 months

Secondary Outcomes (4)

• Overall Response Rate (ORR)

  Up to ~26 months

• Duration of Response (DOR)

  Up to ~42 months

• Number of Participants who Experience an Adverse Event (AE)

  Up to ~42 months

• Number of Participants who Discontinue Study Intervention Due to an AE

  Up to ~24 months

Study Arms (2)

Intismeran Autogene + Pembrolizumab + Chemo

EXPERIMENTAL

Induction phase: Participants receive pembrolizumab 400 mg intravenous (IV) infusion on Day 1 of a six week cycle plus a platinum doublet chemotherapy regimen (carboplatin area under the curve (AUC) 6 or 5 mg/mL/min IV infusion every 3 weeks (Q3W) × 2 doses combined either with paclitaxel 200 or 175 mg/m\^2 IV infusion Q3W × 2 doses, OR with nab paclitaxel 100 mg/m\^2 IV infusion weekly × 6 doses). Intismeran Autogene 1 mg intramuscular (IM) injection is administered on Days 1 and 22 of Cycle 2 Induction (Q3W) for up to 2 doses. Maintenance phase: Participants receive pembrolizumab 400 mg IV infusion on Day 1 every 6 weeks (Q6W) for up to 15 doses. Intismeran Autogene 1 mg IM injection is administered on Days 1 and 22 (Q3W) for up to 7 doses during maintenance.

Biological: Intismeran Autogene; Biological: Pembrolizumab; Drug: Carboplatin; Drug: Paclitaxel; Drug: Nab-paclitaxel

Placebo + Pembrolizumab + Chemo

EXPERIMENTAL

Induction phase: Participants receive pembrolizumab 400 mg intravenous (IV) infusion on Day 1 of a six week cycle plus a platinum doublet chemotherapy regimen (carboplatin area under the curve (AUC) 6 or 5 mg/mL/min IV infusion every 3 weeks (Q3W) × 2 doses combined either with paclitaxel 200 or 175 mg/m\^2 IV infusion Q3W × 2 doses, OR with nab paclitaxel 100 mg/m\^2 IV infusion weekly × 6 doses). Placebo intramuscular (IM) injection is administered on Days 1 and 22 of Cycle 2 Induction (Q3W) for up to 2 doses. Maintenance phase: Participants receive pembrolizumab 400 mg IV infusion on Day 1 every 6 weeks (Q6W) for up to 15 doses. Placebo IM injection is administered on Days 1 and 22 (Q3W) for up to 7 doses during maintenance.

Biological: Pembrolizumab; Drug: Carboplatin; Drug: Paclitaxel; Drug: Nab-paclitaxel; Other: Placebo

Interventions

Pembrolizumab BIOLOGICAL

200 mg IV Infusion

Also known as: MK-3475, KEYTRUDA®

Intismeran Autogene + Pembrolizumab + Chemo; Placebo + Pembrolizumab + Chemo

Intismeran Autogene BIOLOGICAL

1 mg Intramuscular (IM) Injection

Also known as: mRNA-4157, V940

Intismeran Autogene + Pembrolizumab + Chemo

Carboplatin DRUG

Area Under the Curve (AUC) either 6 or 5 (mg/mL/min) IV Infusion

Intismeran Autogene + Pembrolizumab + Chemo; Placebo + Pembrolizumab + Chemo

Paclitaxel DRUG

200 or 175 mg/m\^2 IV Infusion

Intismeran Autogene + Pembrolizumab + Chemo; Placebo + Pembrolizumab + Chemo

Nab-paclitaxel DRUG

100 mg/m\^2 IV Infusion

Intismeran Autogene + Pembrolizumab + Chemo; Placebo + Pembrolizumab + Chemo

Placebo OTHER

Placebo matched to Intismeran Autogene IM injection

Placebo + Pembrolizumab + Chemo

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 or cytologically confirmed diagnosis of squamous non-small cell lung cancer (NSCLC) (Stage IV: M1a, M1b, M1c1, M1c2, AJCC Staging Manual, Version 9). NOTE: Mixed tumors will be characterized by the predominant cell type; however, small cell elements are not permitted.
• Has measurable disease per Response Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as assessed by the local site investigator/radiology
• 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
• Adverse events (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
• Human immunodeficiency virus (HIV)-infected participants must have well controlled HIV on antiretroviral therapy (ART)
• 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
• 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
• Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1 assessed within 7 days before randomization
• Has a life expectancy of at least 3 months
• Has adequate organ function

You may not qualify if:

• Is HIV-infected with a history of Kaposi's sarcoma and/or Multicentric Castleman's Disease
• Has received prior treatment with a cancer vaccine, including another personalized cancer vaccine (PCV)
• Has received prior systemic anticancer therapy for their metastatic NSCLC
• Has received prior therapy with an anti-programmed cell death 1 protein (anti-PD-1), anti-programmed cell death ligand 1 (anti-PD-L1), or anti-programmed cell death ligand 2 (anti-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
• Has received prior radiotherapy within 2 weeks of start of study intervention, or has radiation-related toxicities, requiring corticosteroids
• Has received radiation therapy to the lung that is \>30 gray within 6 months of start of study intervention
• Has received a live or live-attenuated vaccine within 30 days before the first dose of study intervention. Administration of killed vaccines is allowed
• 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 to the first dose of study intervention
• Has known additional malignancy that is progressing or has required active treatment within the past 3 years
• Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis
• Has severe hypersensitivity (≥Grade 3) to V940, pembrolizumab, or any of the protocol allowed chemotherapy agents and/or any of their excipients
• Has active autoimmune disease that has required systemic treatment in the past 2 years
• Has a history of (noninfectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease
• Has active infection requiring systemic therapy

Sponsors & Collaborators

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

Study Sites (51)

Moffitt Cancer Center ( Site 0021)

Tampa, Florida, 33612, United States

RECRUITING

Washington University School of Medicine ( Site 0024)

St Louis, Missouri, 63110, United States

RECRUITING

Valley Health Systems - Ridgewood Campus ( Site 0010)

Paramus, New Jersey, 07652, United States

RECRUITING

Cleveland Clinic - Ohio ( Site 0016)

Cleveland, Ohio, 44195, United States

RECRUITING

Tennessee Oncology, PLLC - Elliston Place Plaza Medical Oncology & Hematology ( Site 9000)

Nashville, Tennessee, 37203, United States

RECRUITING

Texas Oncology - Central/South Texas ( Site 8002)

Austin, Texas, 78745, United States

RECRUITING

Virginia Cancer Specialists ( Site 0003)

Fairfax, Virginia, 22031, United States

RECRUITING

Hospital Italiano de Buenos Aires ( Site 0200)

Ciudad Autonoma de Buenos Aires., Buenos Aires, C1199ABB, Argentina

RECRUITING

Instituto Alexander Fleming ( Site 0201)

Ciudad Autonoma de Buenos Aires, Buenos Aires, C1426ANZ, Argentina

RECRUITING

Instituto de Investigaciones Clínicas Mar del Plata ( Site 0205)

Mar del Plata, Buenos Aires, B7600FZO, Argentina

RECRUITING

Clinica Adventista Belgrano ( Site 0206)

Caba., Buenos Aires F.D., C1430EGF, Argentina

RECRUITING

Fundacion Estudios Clinicos ( Site 0207)

Rosario, Santa Fe Province, S2000DSV, Argentina

RECRUITING

Sanatorio Parque ( Site 0203)

Rosario, Santa Fe Province, S2000DSV, Argentina

RECRUITING

Westmead Hospital ( Site 0400)

Westmead, New South Wales, 2145, Australia

RECRUITING

Princess Alexandra Hospital ( Site 0403)

Woolloongabba, Queensland, 4102, Australia

RECRUITING

One Clinical Research ( Site 0402)

Nedlands, Western Australia, 6009, Australia

RECRUITING

Centro de Estudios Clínicos SAGA ( Site 0307)

Santiago, Region M. de Santiago, 7500653, Chile

RECRUITING

FALP ( Site 0300)

Santiago, Region M. de Santiago, 7500921, Chile

RECRUITING

Bradfordhill ( Site 0301)

Santiago, Region M. de Santiago, 8420383, Chile

RECRUITING

Bradford Hill Norte ( Site 0308)

Antofagasta, 1263521, Chile

RECRUITING

Centre Georges François Leclerc ( Site 0805)

Dijon, Cote-d Or, 21000, France

RECRUITING

Institut de Cancérologie de l'Ouest ( Site 0801)

Angers, Pays de la Loire Region, 49055, France

RECRUITING

CHU GABRIEL MONTPIED ( Site 0802)

Clermont-Ferrand, Puy-de-Dome, 63001, France

RECRUITING

Ospedale Santa Maria delle Croci-Dipartimento Oncoematologico ( Site 1004)

Ravenna, Emilia-Romagna, 48121, Italy

RECRUITING

Ospedale San Raffaele-Oncologia Medica ( Site 1002)

Milan, 20132, Italy

RECRUITING

Fondazione IRCCS Istituto Nazionale Dei Tumori ( Site 1000)

Milan, 20133, Italy

RECRUITING

Fondazione Policlinico Universitario Agostino Gemelli IRCCS - Università Cattolica del Sacro Cuore ( Site 1001)

Roma, 00168, Italy

RECRUITING

Wielkopolskie Centrum Pulmonologii i Torakochirurgii ( Site 1101)

Poznan, Greater Poland Voivodeship, 60-569, Poland

RECRUITING

Narodowy Instytut Onkologii im. Marii Sklodowskiej-Curie - Panstwowy Instytut Badawczy w Warszawie ( Site 1100)

Warsaw, Masovian Voivodeship, 02-781, Poland

RECRUITING

Wojewodzki Szpital im. Sw. Ojca Pio w Przemyslu ( Site 1102)

Przemyśl, Podkarpackie Voivodeship, 37-700, Poland

RECRUITING

National Cancer Center ( Site 0504)

Goyang-si, Kyonggi-do, 10408, South Korea

RECRUITING

Seoul National University Bundang Hospital ( Site 0500)

Seongnam-si, Kyonggi-do, 13620, South Korea

RECRUITING

Chungbuk National University Hospital-Internal medicine ( Site 0501)

Cheongju-si, North Chungcheong, 28644, South Korea

RECRUITING

Asan Medical Center ( Site 0503)

Seoul, 05505, South Korea

RECRUITING

Samsung Medical Center ( Site 0502)

Seoul, 06351, South Korea

RECRUITING

ICO L Hospitalet ( Site 1311)

Hospitalet, Barcelona, 08907, Spain

RECRUITING

Hospital Jerez de la Frontera-UGC Oncología ( Site 1315)

Jerez de la Frontera, Cadiz, 11407, Spain

RECRUITING

Hospital Universitari Vall d''Hebron ( Site 1310)

Barcelona, 08035, Spain

RECRUITING

Hospital Ramon y Cajal ( Site 1314)

Madrid, 28034, Spain

RECRUITING

Hospital Clinico San Carlos... ( Site 1313)

Madrid, 28040, Spain

RECRUITING

Hospital Universitario Virgen Macarena-Unidad de Investigación Oncológica ( Site 1312)

Seville, 41009, Spain

RECRUITING

China Medical University Hospital ( Site 0606)

Taichung, 404, Taiwan

RECRUITING

National Cheng Kung University Hospital ( Site 0601)

Tainan, 70403, Taiwan

RECRUITING

Mackay Memorial Hospital ( Site 0604)

Taipei, 104, Taiwan

RECRUITING

National Taiwan University Cancer Center (NTUCC) ( Site 0600)

Taipei, 106, Taiwan

RECRUITING

Taipei Veterans General Hospital ( Site 0602)

Taipei, 11217, Taiwan

RECRUITING

Chang Gung Medical Foundation-Linkou Branch ( Site 0605)

Taoyuan, 33305, Taiwan

RECRUITING

Hacettepe Universitesi Tıp Fakultesi ( Site 1400)

Ankara, 06230, Turkey (Türkiye)

RECRUITING

Memorial Ankara Hastanesi ( Site 1401)

Ankara, 06520, Turkey (Türkiye)

RECRUITING

Ankara Bilkent Şehir Hastanesi ( Site 1402)

Ankara, 06800, Turkey (Türkiye)

RECRUITING

Koç Üniversitesi Hastanesi ( Site 1403)

Istanbul, 34010, Turkey (Türkiye)

RECRUITING

Related Links

• Merck Clinical Trials Information
• Plain Language Summary

MeSH Terms

Interventions

pembrolizumab; Carboplatin; Paclitaxel; 130-nm albumin-bound paclitaxel

Intervention Hierarchy (Ancestors)

Coordination Complexes; Organic Chemicals; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Diterpenes; Terpenes

Study Officials

• Medical Director

  Merck Sharp & Dohme LLC

  STUDY DIRECTOR

Central Study Contacts

Toll Free Number

CONTACT

1-888-577-8839; Trialsites@msd.com

Study Design

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

Study Record Dates

• First Submitted: October 24, 2025
• First Posted: October 28, 2025
• Study Start: December 12, 2025
• Primary Completion (Estimated): July 2, 2029
• Study Completion (Estimated): May 6, 2031
• Last Updated: June 9, 2026

Record last verified: 2026-06

Data Sharing

• IPD Sharing: Will share

Locations

AR (6); ES (6); TU (4); PL (3); TW (6); KR (5); US (7); AU (3); FR (3); CL (4); IT (4)