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Comparing two treatments for advanced non-small cell lung cancer

An Open-label, Multicenter, Phase 3 Randomized, Active-Comparator-Controlled Clinical Study of Pembrolizumab (MK-3475) in Combination With Sacituzumab Govitecan Versus MK-3475 Monotherapy as First-line Treatment in Participants With PD L1 TPS Greater Than or Equal to 50% Metastatic Non-small Cell Lung Cancer (KEYNOTE D46/EVOKE-03)

Phase 3 Interventional Merck Sharp & Dohme LLC · NCT05609968

This study is testing whether a combination of two cancer treatments works better than just one for people with advanced non-small cell lung cancer.

Quick facts

PhasePhase 3
Study typeInterventional
Enrollment614 (estimated)
Ages18 Years and up
SexAll
SponsorMerck Sharp & Dohme LLC Industry-sponsored
Drugs / interventionspembrolizumab, sacituzumab, chemotherapy, radiation
Locations166 sites (Mobile, Alabama and 165 other locations)
Trial IDNCT05609968 on ClinicalTrials.gov

What this trial studies

This study aims to evaluate the effectiveness of pembrolizumab alone versus pembrolizumab combined with sacituzumab govitecan in patients with metastatic non-small cell lung cancer (NSCLC) who have a PD-L1 tumor proportion score of 50% or higher. The primary focus is on measuring progression-free survival and overall survival using standardized assessment criteria. Participants will be monitored for their response to treatment through independent reviews of their tumor progression.

Who should consider this trial

Good fit: Ideal candidates are adults with metastatic non-small cell lung cancer and a PD-L1 tumor proportion score of 50% or higher.

Not a fit: Patients who have received prior systemic chemotherapy or targeted therapies for their metastatic NSCLC may not benefit from this study.

Why it matters

Potential benefit: If successful, this study could provide a more effective treatment option for patients with advanced non-small cell lung cancer.

How similar studies have performed: Previous studies have shown promising results with similar immunotherapy approaches in treating advanced lung cancer.

Eligibility criteria

Show full inclusion / exclusion criteria 
Inclusion Criteria:

The main inclusion criteria include but are not limited to the following:

* Has a histologically or cytologically confirmed diagnosis of metastatic non-small cell lung cancer (NSCLC)
* Has confirmation that epidermal growth factor receptor (EGFR), anaplastic lymphoma kinase 1 (ALK-1), or ROS proto-oncogene 1 (ROS-1)-directed therapy is not indicated as primary therapy
* Has provided tumor tissue that demonstrates PD-L1 tumor proportion score (TPS) ≥50% of tumor cells as assessed by immunohistochemistry (IHC) at a central laboratory
* Has a life expectancy of at least 3 months

Exclusion Criteria:

The main exclusion criteria include but are not limited to the following:

* Has history of a second malignancy, unless potentially curative treatment has been completed with no evidence of malignancy for 3 years
* Has received prior systemic chemotherapy or other targeted or biological antineoplastic therapy for their metastatic NSCLC
* Has previously received treatment with Topoisomerase 1 inhibitors or Trop-2 targeted therapy
* 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 anti- programmed cell death ligand 2 (PD-L2) agent or with an agent directed to another stimulatory or coinhibitory T-cell receptor
* 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 (Gy) within 6 months of the first dose of study intervention
* Has received a live or live-attenuated vaccine within 30 days before the first dose of study intervention
* Has received an investigational agent or has used an investigational device within 4 weeks before study intervention administration
* Has cardiac disease

  * Myocardial infarction or unstable angina pectoris within 6 months of enrollment
  * History of serious ventricular arrhythmia, high-grade atrioventricular block, or other cardiac arrhythmias requiring antiarrhythmic medications; history of QT interval prolongation
  * New York Heart Association (NYHA) Class III or greater congestive heart failure or left ventricular ejection fraction of \<40%
* Has active chronic inflammatory bowel disease
* Has diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior the first dose of study medication
* Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis
* Has severe hypersensitivity (≥Grade 3) to pembrolizumab or sacituzumab govitecan and/or any of their excipients
* Has active autoimmune disease that has required systemic treatment in past 2 years except replacement therapy
* History of (noninfectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease
* Has active infection requiring systemic therapy
* Has history of human immunodeficiency virus (HIV) infection
* History of hepatitis B or known active hepatitis C virus infection
* Has history or current evidence of any condition, therapy, laboratory abnormality, or other circumstance that might confound the results of the study or interfere with the participant's participation for the full duration of the study, such that it is not in the best interest of the participant to participate, in the opinion of the treating investigator
* Have not adequately recovered from major surgery or have ongoing surgical complications

Where this trial is running

Mobile, Alabama and 165 other locations

+116 more sites — see ClinicalTrials.gov for the full list.

Study contacts

How to participate

  1. Review the eligibility criteria above with your treating physician.
  2. Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
  3. Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.
View on ClinicalTrials.gov → Find more trials like this →
Conditions Carcinoma, Non-Small-Cell LungProgrammed Cell Death-1Programmed Death-Ligand 1Programmed Cell Death-2Programmed Death-Ligand 2Trophoblast Cell Surface Antigen-2Antibody-Drug Conjugate
Last reviewed 2026-06-13 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.