Recruiting
Phase 2

V940 with Pembrolizumab, Chemotherapy

Sponsor:

Merck Sharp & Dohme LLC

Code:

NCT07221474

Conditions

Squamous Non-small Cell Lung Cancer

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Interventions

Intismeran Autogene

Pembrolizumab

Carboplatin

Paclitaxel

Nab-paclitaxel

Study Details

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

Study ID

NCT07221474

Start date

Dec 12, 2025

Status verified date

Aug, 2026

Completion date

May 6, 2031

Anticipated

Primary completion date

Jul 2, 2029

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

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 Design

Enrollment

180 participants

Anticipated

Allocation

Randomized

Intervention Model

Parallel Assignment

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

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.

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.

Interventions

Intismeran Autogene

1 mg Intramuscular (IM) Injection

Pembrolizumab

200 mg IV Infusion

Carboplatin

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

Paclitaxel

200 or 175 mg/m\^2 IV Infusion

Nab-paclitaxel

100 mg/m\^2 IV Infusion

Placebo

Placebo matched to Intismeran Autogene IM injection

Primary outcome measure

  • Progression Free Survival (PFS) [ Time Frame: Up to ~32 months ]
  • Overall Survival (OS) [ Time Frame: Up to ~42 months ]

Central Contacts and Locations

Central contacts

Toll Free Number

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

Locations

Moffitt Cancer Center ( Site 0021)

Recruiting

Tampa, Florida, United States, 33612

Contacts

Study Coordinator

813-745-7363

VA Ann Arbor Healthcare System ( Site 0019)

Recruiting

Ann Arbor, Michigan, United States, 48105

Contacts

Study Coordinator

734-769-7100

Washington University School of Medicine ( Site 0024)

Recruiting

St Louis, Missouri, United States, 63110

Contacts

Study Coordinator

314-362-5000

Valley Health Systems - Ridgewood Campus ( Site 0010)

Recruiting

Paramus, New Jersey, United States, 07652

Contacts

Study Coordinator

201-634-5578

New York Oncology Hematology (NYOH) - Albany Medical Center ( Site 9001)

Recruiting

Albany, New York, United States, 12206

Contacts

Study Coordinator

518-489-0044

Cleveland Clinic - Ohio ( Site 0016)

Recruiting

Cleveland, Ohio, United States, 44195

Contacts

Study Coordinator

216-445-7855

Good Samaritan Regional Medical Center-Samaritan Pastega Regional Cancer Center ( Site 0025)

Recruiting

Corvallis, Oregon, United States, 97330

Contacts

Study Coordinator

541-768-4950

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

Recruiting

Nashville, Tennessee, United States, 37203

Contacts

Study Coordinator

615-961-9469

Texas Oncology - Central/South Texas ( Site 8002)

Recruiting

Austin, Texas, United States, 78745

Contacts

Study Coordinator

512-427-9400

Virginia Cancer Specialists ( Site 0003)

Recruiting

Fairfax, Virginia, United States, 22031

Contacts

Study Coordinator

730-280-5390

Swedish Medical Center-Swedish Cancer Institute ( Site 0023)

Recruiting

Seattle, Washington, United States, 98104

Contacts

Study Coordinator

855-922-6237

More Information

Sponsor

Merck Sharp & Dohme LLC

Last update posted

Aug 21, 2026

Last verified

Aug, 2026

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-08. This information was provided to ClinicalTrials.gov by Merck Sharp & Dohme LLC on 2026-08-21.