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Combining pembrolizumab with or without sacituzumab tirumotecan for advanced lung cancer treatment

Phase 3 Study of Pembrolizumab in Combination With Carboplatin/Taxane (Paclitaxel or Nab-paclitaxel) Followed by Pembrolizumab With or Without Maintenance MK-2870 in the First-line Treatment of Metastatic Squamous Non-small Cell Lung Cancer

Phase 3 Interventional Merck Sharp & Dohme LLC · NCT06422143

This study is testing if adding a new drug called sacituzumab tirumotecan to the standard treatment with pembrolizumab can help people with advanced lung cancer live longer.

Quick facts

PhasePhase 3
Study typeInterventional
Enrollment851 (estimated)
Ages18 Years and up
SexAll
SponsorMerck Sharp & Dohme LLC Industry-sponsored
Drugs / interventionschemotherapy, radiation, pembrolizumab, sacituzumab
Locations207 sites (Little Rock, Arkansas and 206 other locations)
Trial IDNCT06422143 on ClinicalTrials.gov

What this trial studies

This phase 3 study investigates the effectiveness of pembrolizumab combined with carboplatin and paclitaxel or nab-paclitaxel as a first-line treatment for metastatic squamous non-small cell lung cancer (NSCLC). Participants will undergo an initial induction phase followed by random assignment to receive either pembrolizumab alone or pembrolizumab with maintenance sacituzumab tirumotecan. The primary goal is to determine if the combination therapy improves overall survival compared to pembrolizumab alone. The study aims to provide insights into the potential benefits of adding sacituzumab tirumotecan to standard treatment.

Who should consider this trial

Good fit: Ideal candidates are adults with histologically confirmed metastatic squamous non-small cell lung cancer who have a good performance status and measurable disease.

Not a fit: Patients with non-squamous NSCLC or those with a poor performance status may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment approach could significantly improve survival rates for patients with metastatic squamous NSCLC.

How similar studies have performed: Other studies have shown promising results with similar immunotherapy combinations, suggesting potential for success in this approach.

Eligibility criteria

Show full inclusion / exclusion criteria 
Inclusion Criteria:

* Histologically or cytologically confirmed diagnosis of squamous non-small cell lung cancer (NSCLC) \[Stage IV: M1a, M1b, M1c, American Joint Committee on Cancer Staging Manual, version 8\]
* Measurable disease per Response Evaluation Criteria in Solid Tumours (RECIST) 1.1 as assessed by the local site investigator/radiology
* Has life expectancy ≥3 months
* Has Eastern Cooperative Oncology Group Performance Status (ECOG PS) score of 0 or 1 assessed within 7 days prior to allocation
* Archival tumor tissue sample or newly obtained core, incisional, or excisional biopsy of a tumor lesion not previously irradiated has been provided
* Human immunodeficiency virus (HIV)-infected participants must have well controlled HIV on antiretroviral therapy (ART)
* Participants who are hepatitis B surface antigen (HBsAg)-positive are eligible if they have received hepatitis B virus (HBV) antiviral therapy for at least 4 weeks and have undetectable HBV viral load before allocation
* Participants with history of hepatitis C virus (HCV) infection are eligible if HCV viral load is undetectable at screening
* Participants who have adverse events (AEs) due to previous anticancer therapies must have recovered to Grade ≤1 or baseline (participants with endocrine-related AEs who are adequately treated with hormone replacement are eligible)
* Has adequate organ function
* For Maintenance only (prior to randomization): is without disease progression of their NSCLC, as determined by BICR using RECIST 1.1 after completion of study-specified Induction with an evaluable scan at Week 12 or most recent scan before randomization
* For Maintenance only (prior to randomization): has ECOG PS of 0 or 1 as assessed at the Prerandomization Visit
* For Maintenance only (prior to randomization): all AEs (with the exception of alopecia, Grade ≤2 fatigue, Grade ≤2 peripheral neuropathy, and Grade ≤2 endocrine-related AEs requiring treatment or hormone replacement) have recovered
* For Maintenance only (prior to randomization): has not experienced a pneumonitis/interstitial lung disease (ILD) event during the study-specified induction

Exclusion Criteria:

* Diagnosis of small cell lung cancer or, for mixed tumors, presence of small cell elements
* History of documented severe dry eye syndrome, severe Meibomian gland disease and/or blepharitis, or severe corneal disease that prevents/delays corneal healing
* Active inflammatory bowel disease requiring immunosuppressive medication or previous history of inflammatory bowel disease (eg, Crohn's disease, ulcerative colitis, or chronic diarrhea)
* Has uncontrolled, significant cardiovascular disease or cerebrovascular disease including New York Heart Association Class III or IV congestive heart failure, unstable angina, myocardial infarction, uncontrolled symptomatic arrhythmia, prolongation of QTcF interval to \>480 ms, and other serious cardiovascular and cerebrovascular diseases within 6 months before study intervention
* HIV-infected participants who have been newly diagnosed or with a history of Kaposi's sarcoma and/or Multicentric Castleman's Disease
* Received prior systemic chemotherapy or other targeted or biological antineoplastic therapy for their metastatic NSCLC. Note: Prior treatment with chemotherapy and/or radiation as a part of neoadjuvant or adjuvant therapy or chemoradiation therapy for nonmetastatic NSCLC is allowed as long as therapy was completed at least 12 months before diagnosis of metastatic NSCLC
* 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 (eg, cytotoxic T lymphocyte-associated protein 4, OX-40, CD137). Note: Prior treatment with an anti-PD-1 or anti-PD-L1 agent for nonmetastatic NSCLC is allowed as long as therapy was completed at least 12 months before diagnosis of metastatic NSCLC
* Received prior treatment with a trophoblast cell-surface antigen 2 (TROP2)-targeted antidrug conjugate (ADC)
* Received radiation therapy to the lung that is \>30 Gray within 6 months of start of study intervention
* Received prior radiotherapy within 2 weeks of start of study intervention, or radiation-related toxicities, requiring corticosteroids
* Received a live or live-attenuated vaccine within 30 days before the first dose of study intervention
* Participants who have not adequately recovered from major surgery or have ongoing surgical complications
* Received prior treatment with a topoisomerase I inhibitor-containing ADC
* Is currently receiving a strong inducer/inhibitor of CYP3A4 that cannot be discontinued for the duration of the study (the required washout period before starting sac-TMT is 2 weeks)
* Has a known additional malignancy that is progressing or has required active treatment within the past 3 years.
* Has known central nervous system (CNS) metastases/carcinomatous meningitis
* Severe hypersensitivity (≥Grade 3) to study intervention and/or any of its excipients or to another biologic therapy
* Active autoimmune disease that has required systemic treatment in the past 2 years (replacement therapy \[eg, thyroxine, insulin, or physiologic corticosteroid\] is allowed)
* Has a history of (noninfectious)pneumonitis/ILD that required steroids, has current pneumonitis/ILD, or has suspected ILD or pneumonitis that cannot be ruled out by standard diagnostic assessments at Screening
* Active infection requiring systemic therapy
* History of allogeneic tissue/solid organ transplant

Where this trial is running

Little Rock, Arkansas and 206 other locations

+157 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 Non-small Cell Lung CancerNSCLC
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.