A Study of Intismeran Autogene (V940)/Placebo + Pembrolizumab and Chemotherapy in Metastatic Squamous Non-Small Cell Lung Cancer (V940-013) (INTerpath-13)

A Phase 2, Randomized, Double-Blind, Placebo-Controlled Study of V940 in Combination With Pembrolizumab and Chemotherapy as First-Line Treatment for Participants With Metastatic Squamous NSCLC (INTerpath-013)

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.

Study Overview

• Status: Recruiting
• Conditions: Squamous Non-small Cell Lung Cancer
• Intervention / Treatment: Biological: Pembrolizumab; Drug: Nab-paclitaxel; Biological: Intismeran Autogene; Other: Placebo; Drug: Carboplatin; Drug: Paclitaxel

• Study Type: Interventional
• Enrollment (Estimated): 180
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Toll Free Number; Phone Number: 1-888-577-8839; Email: Trialsites@msd.com

Study Locations

• Argentina
  • Buenos Aires
    • Ciudad Autonoma de Buenos Aires, Buenos Aires, Argentina, C1426ANZ
      • Recruiting
      • Instituto Alexander Fleming ( Site 0201)
      • Contact: Study Coordinator; Phone Number: +541132218956
    • Ciudad Autonoma de Buenos Aires., Buenos Aires, Argentina, C1199ABB
      • Recruiting
      • Hospital Italiano de Buenos Aires ( Site 0200)
      • Contact: Study Coordinator; Phone Number: +541149590497
    • Mar del Plata, Buenos Aires, Argentina, B7600FZO
      • Recruiting
      • Instituto de Investigaciones Clínicas Mar del Plata ( Site 0205)
      • Contact: Study Coordinator; Phone Number: +5492235937663
  • Buenos Aires F.D.
    • Caba., Buenos Aires F.D., Argentina, C1430EGF
      • Recruiting
      • Clinica Adventista Belgrano ( Site 0206)
      • Contact: Study Coordinator; Phone Number: +5491140141500
  • Santa Fe Province
    • Rosario, Santa Fe Province, Argentina, S2000DSV
      • Recruiting
      • Fundacion Estudios Clinicos ( Site 0207)
      • Contact: Study Coordinator; Phone Number: +5493413168137
    • Rosario, Santa Fe Province, Argentina, S2000DSV
      • Recruiting
      • Sanatorio Parque ( Site 0203)
      • Contact: Study Coordinator; Phone Number: +543874044942
• Australia
  • New South Wales
    • Westmead, New South Wales, Australia, 2145
      • Recruiting
      • Westmead Hospital ( Site 0400)
      • Contact: Study Coordinator; Phone Number: +61298455555
  • Queensland
    • Woolloongabba, Queensland, Australia, 4102
      • Recruiting
      • Princess Alexandra Hospital ( Site 0403)
      • Contact: Study Coordinator; Phone Number: +61731762111
  • Western Australia
    • Nedlands, Western Australia, Australia, 6009
      • Recruiting
      • One Clinical Research ( Site 0402)
      • Contact: Study Coordinator; Phone Number: +6186279 9466
• Chile
  • Antofagasta, Chile, 1263521
    • Recruiting
    • Bradford Hill Norte ( Site 0308)
    • Contact: Study Coordinator; Phone Number: 56442023631
  • Region M. de Santiago
    • Santiago, Region M. de Santiago, Chile, 7500653
      • Recruiting
      • Centro de Estudios Clínicos SAGA ( Site 0307)
      • Contact: Study Coordinator; Phone Number: +56991612199
    • Santiago, Region M. de Santiago, Chile, 8420383
      • Recruiting
      • Bradfordhill ( Site 0301)
      • Contact: Study Coordinator; Phone Number: +56 2 29490970
    • Santiago, Region M. de Santiago, Chile, 7500921
      • Recruiting
      • FALP ( Site 0300)
      • Contact: Study Coordinator; Phone Number: 56224205098
• France
  • Cote-d Or
    • Dijon, Cote-d Or, France, 21000
      • Recruiting
      • Centre Georges François Leclerc ( Site 0805)
      • Contact: Study Coordinator; Phone Number: +33345348051
  • Pays de la Loire Region
    • Angers, Pays de la Loire Region, France, 49055
      • Recruiting
      • Institut de Cancérologie de l'Ouest ( Site 0801)
      • Contact: Study Coordinator; Phone Number: +33 (0)2.44 85 35 54
  • Puy-de-Dome
    • Clermont-Ferrand, Puy-de-Dome, France, 63001
      • Recruiting
      • CHU GABRIEL MONTPIED ( Site 0802)
      • Contact: Study Coordinator; Phone Number: +33473754440
• Italy
  • Roma, Italy, 00168
    • Recruiting
    • Fondazione Policlinico Universitario Agostino Gemelli IRCCS - Università Cattolica del Sacro Cuore ( Site 1001)
    • Contact: Study Coordinator; Phone Number: 00390630154277
• Poland
  • Greater Poland Voivodeship
    • Poznan, Greater Poland Voivodeship, Poland, 60-569
      • Recruiting
      • Wielkopolskie Centrum Pulmonologii i Torakochirurgii ( Site 1101)
      • Contact: Study Coordinator; Phone Number: +48616654242
  • Masovian Voivodeship
    • Warsaw, Masovian Voivodeship, Poland, 02-781
      • Recruiting
      • Narodowy Instytut Onkologii im. Marii Sklodowskiej-Curie - Panstwowy Instytut Badawczy w Warszawie ( Site 1100)
      • Contact: Study Coordinator; Phone Number: +48225463066
  • Podkarpackie Voivodeship
    • Przemyśl, Podkarpackie Voivodeship, Poland, 37-700
      • Recruiting
      • Wojewodzki Szpital im. Sw. Ojca Pio w Przemyslu ( Site 1102)
      • Contact: Study Coordinator; Phone Number: +48166775000
• South Korea
  • Seoul, South Korea, 05505
    • Recruiting
    • Asan Medical Center ( Site 0503)
    • Contact: Study Coordinator; Phone Number: +82230103215
  • Seoul, South Korea, 06351
    • Recruiting
    • Samsung Medical Center ( Site 0502)
    • Contact: Study Coordinator; Phone Number: +82234101132
  • Kyonggi-do
    • Goyang-si, Kyonggi-do, South Korea, 10408
      • Recruiting
      • National Cancer Center ( Site 0504)
      • Contact: Study Coordinator; Phone Number: +82319200114
    • Seongnam-si, Kyonggi-do, South Korea, 13620
      • Recruiting
      • Seoul National University Bundang Hospital ( Site 0500)
      • Contact: Study Coordinator; Phone Number: +82317877071
  • North Chungcheong
    • Cheongju-si, North Chungcheong, South Korea, 28644
      • Recruiting
      • Chungbuk National University Hospital-Internal medicine ( Site 0501)
      • Contact: Study Coordinator; Phone Number: 043-269-6015
• Spain
  • Barcelona, Spain, 08035
    • Recruiting
    • Hospital Universitari Vall d''Hebron ( Site 1310)
    • Contact: Study Coordinator; Phone Number: +34 93 254 3450
  • Madrid, Spain, 28034
    • Recruiting
    • Hospital Ramon y Cajal ( Site 1314)
    • Contact: Study Coordinator; Phone Number: +34 91 336 82 63
  • Madrid, Spain, 28040
    • Recruiting
    • Hospital Clinico San Carlos... ( Site 1313)
    • Contact: Study Coordinator; Phone Number: +34 913303000
  • Seville, Spain, 41009
    • Recruiting
    • Hospital Universitario Virgen Macarena-Unidad de Investigación Oncológica ( Site 1312)
    • Contact: Study Coordinator; Phone Number: +34 671560092
  • Barcelona
    • Hospitalet, Barcelona, Spain, 08907
      • Recruiting
      • ICO L Hospitalet ( Site 1311)
      • Contact: Study Coordinator; Phone Number: +34 93 260 77 44
  • Cadiz
    • Jerez de la Frontera, Cadiz, Spain, 11407
      • Recruiting
      • Hospital Jerez de la Frontera-UGC Oncología ( Site 1315)
      • Contact: Study Coordinator; Phone Number: 956 03 22 44
• Taiwan
  • Tainan, Taiwan, 70403
    • Recruiting
    • National Cheng Kung University Hospital ( Site 0601)
    • Contact: Study Coordinator; Phone Number: +88662353535
  • Taipei, Taiwan, 104
    • Recruiting
    • Mackay Memorial Hospital ( Site 0604)
    • Contact: Study Coordinator; Phone Number: +886225433535
  • Taipei, Taiwan, 11217
    • Recruiting
    • Taipei Veterans General Hospital ( Site 0602)
    • Contact: Study Coordinator; Phone Number: +88628712121
  • Taipei, Taiwan, 106
    • Recruiting
    • National Taiwan University Cancer Center (NTUCC) ( Site 0600)
    • Contact: Study Coordinator; Phone Number: +886223220322
  • Taoyuan, Taiwan, 33305
    • Recruiting
    • Chang Gung Medical Foundation-Linkou Branch ( Site 0605)
    • Contact: Study Coordinator; Phone Number: +88633281200
• Turkey (Türkiye)
  • Ankara, Turkey (Türkiye), 06230
    • Recruiting
    • Hacettepe Universitesi Tıp Fakultesi ( Site 1400)
    • Contact: Study Coordinator; Phone Number: +905436067759
  • Ankara, Turkey (Türkiye), 06800
    • Recruiting
    • Ankara Bilkent Şehir Hastanesi ( Site 1402)
    • Contact: Study Coordinator; Phone Number: +905384724282
  • Ankara, Turkey (Türkiye), 06520
    • Recruiting
    • Memorial Ankara Hastanesi ( Site 1401)
    • Contact: Study Coordinator; Phone Number: +9005321332009
  • Istanbul, Turkey (Türkiye), 34010
    • Recruiting
    • Koç Üniversitesi Hastanesi ( Site 1403)
    • Contact: Study Coordinator; Phone Number: +905369410661
• United States
  • Florida
    • Tampa, Florida, United States, 33612
      • Recruiting
      • Moffitt Cancer Center ( Site 0021)
      • Contact: Study Coordinator; Phone Number: 813-745-7363
  • Missouri
    • St Louis, Missouri, United States, 63110
      • Recruiting
      • Washington University School of Medicine ( Site 0024)
      • Contact: Study Coordinator; Phone Number: 314-362-5000
  • New Jersey
    • Paramus, New Jersey, United States, 07652
      • Recruiting
      • Valley Health Systems - Ridgewood Campus ( Site 0010)
      • Contact: Study Coordinator; Phone Number: 201-634-5578
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • Recruiting
      • Cleveland Clinic - Ohio ( Site 0016)
      • Contact: Study Coordinator; Phone Number: 216-445-7855
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • Recruiting
      • Tennessee Oncology, PLLC - Elliston Place Plaza Medical Oncology & Hematology ( Site 9000)
      • Contact: Study Coordinator; Phone Number: 615-961-9469
  • Texas
    • Austin, Texas, United States, 78745
      • Recruiting
      • Texas Oncology - Central/South Texas ( Site 8002)
      • Contact: Study Coordinator; Phone Number: 512-427-9400
  • Virginia
    • Fairfax, Virginia, United States, 22031
      • Recruiting
      • Virginia Cancer Specialists ( Site 0003)
      • Contact: Study Coordinator; Phone Number: 730-280-5390

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

Inclusion Criteria include, but are not limited to:

• 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

Exclusion Criteria:

Exclusion Criteria include, but are not limited to:

• 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
• Has a history of stem cell/solid organ transplant
• Has not adequately recovered from major surgery or has ongoing surgical complications

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Intismeran Autogene + Pembrolizumab + Chemo; 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: Pembrolizumab; 200 mg IV Infusion; Other Names: MK-3475; KEYTRUDA®; Drug: Nab-paclitaxel; 100 mg/m^2 IV Infusion; Biological: Intismeran Autogene; 1 mg Intramuscular (IM) Injection; Other Names: mRNA-4157; V940; Drug: Carboplatin; Area Under the Curve (AUC) either 6 or 5 (mg/mL/min) IV Infusion; Drug: Paclitaxel; 200 or 175 mg/m^2 IV Infusion
Experimental: Placebo + Pembrolizumab + Chemo; 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; 200 mg IV Infusion; Other Names: MK-3475; KEYTRUDA®; Drug: Nab-paclitaxel; 100 mg/m^2 IV Infusion; Other: Placebo; Placebo matched to Intismeran Autogene IM injection; Drug: Carboplatin; Area Under the Curve (AUC) either 6 or 5 (mg/mL/min) IV Infusion; Drug: Paclitaxel; 200 or 175 mg/m^2 IV Infusion

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Response Rate (ORR)	ORR is defined as the percentage of participants with Complete Response (CR: disappearance of all target lesions) or Partial Response (PR: at least a 30% decrease in the sum of diameters of target lesions) per RECIST 1.1. The percentage of participants who experience CR or PR as assessed by BICR will be presented.	Up to ~26 months
Duration of Response (DOR)	For participants who demonstrate a confirmed Complete Response (CR: disappearance of all target lesions) or Partial Response (PR: at least a 30% decrease in the sum of diameters of target lesions) per RECIST 1.1, DOR is defined as the time from first documented evidence of CR or PR until progressive disease (PD) or death. Per RECIST 1.1, PD is defined as at least a 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 at least 5 mm. The appearance of one or more new lesions is also considered PD. DOR as assessed by BICR will be presented.	Up to ~42 months
Number of Participants who Experience an Adverse Event (AE)	An AE is defined as any unfavorable and unintended sign, symptom, disease, or worsening of preexisting condition temporally associated with study treatment and irrespective of causality to study treatment. The number of participants who experience an AE will be presented.	Up to ~42 months
Number of Participants who Discontinue Study Intervention Due to an AE	An AE is defined as any unfavorable and unintended sign, symptom, disease, or worsening of preexisting condition temporally associated with study treatment and irrespective of causality to study treatment. The number of participants who discontinue study intervention due to an AE will be presented.	Up to ~24 months

Collaborators and Investigators

• Sponsor: Merck Sharp & Dohme LLC
• Collaborators: ModernaTX, Inc.
• Investigators: Study Director: Medical Director, Merck Sharp & Dohme LLC

Publications and helpful links

Helpful Links

• Merck Clinical Trials Information
• Plain Language Summary

Study record dates

Study Major Dates

• Study Start (Actual): December 12, 2025
• Primary Completion (Estimated): July 2, 2029
• Study Completion (Estimated): May 6, 2031

Study Registration Dates

• First Submitted: October 24, 2025
• First Submitted That Met QC Criteria: October 24, 2025
• First Posted (Actual): October 28, 2025

Study Record Updates

• Last Update Posted (Actual): May 28, 2026
• Last Update Submitted That Met QC Criteria: May 27, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Organic Chemicals; Hydrocarbons; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Terpenes; Coordination Complexes; Taxoids; Cyclodecanes; Diterpenes; Carboplatin; Paclitaxel; pembrolizumab; 130-nm albumin-bound paclitaxel
• Other Study ID Numbers: V940-013 (Other Identifier: MSD); U1111-1318-2495 (Registry Identifier: UTN); 2025-520902-37-00 (Registry Identifier: EU CT)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: https://trialstransparency.msdclinicaltrials.com/pdf/ProcedureAccessClinicalTrialData.pdf

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No