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Combining Pembrolizumab with Chemotherapy and Other Treatments for Advanced Lung Cancer

KEYMAKER-U01 Substudy 01G: A Phase 2, Umbrella Study With Rolling Arms of Investigational Agents in Combination With Pembrolizumab With or Without Platinum-based Chemotherapy in Treatment-Naïve Participants With Stage IV Non-small Cell Lung Cancer (NSCLC)

Phase 2 Interventional Merck Sharp & Dohme LLC · NCT06731907

This study is testing if combining the immunotherapy drug pembrolizumab with chemotherapy and other treatments can help people with untreated advanced lung cancer feel better and live longer.

Quick facts

PhasePhase 2
Study typeInterventional
Enrollment90 (estimated)
Ages18 Years and up
SexAll
SponsorMerck Sharp & Dohme LLC Industry-sponsored
Drugs / interventionsradiation, pembrolizumab, patritumab, chemotherapy, immunotherapy
Locations41 sites (Lexington, Kentucky and 40 other locations)
Trial IDNCT06731907 on ClinicalTrials.gov

What this trial studies

This study investigates new treatment options for patients with untreated advanced non-small cell lung cancer (NSCLC), the most common type of lung cancer. Researchers are evaluating the effectiveness of pembrolizumab, an immunotherapy drug, in combination with chemotherapy and additional treatments like the HER3-directed antibody-drug conjugate patritumab deruxtecan. The primary focus is on assessing the safety and efficacy of these combinations in patients with Stage IV NSCLC. Participants will be monitored for their response to the treatments and any potential side effects.

Who should consider this trial

Good fit: Ideal candidates include individuals with Stage IV squamous or non-squamous NSCLC who have not received prior treatment.

Not a fit: Patients with early-stage lung cancer or those who have already undergone extensive treatment 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: Other studies have shown promise with similar immunotherapy and chemotherapy combinations, suggesting potential for success in this approach.

Eligibility criteria

Show full inclusion / exclusion criteria 
Inclusion Criteria:

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

* Histologically or cytologically confirmed diagnosis of Stage IV squamous or non-squamous non-small cell lung cancer (NSCLC) per American Joint Committee on Cancer (AJCC) Staging Manual Version 8.
* Has an Eastern Cooperative Oncology Group (ECOG) performance status of either 0 or 1 as assessed within 7 days before randomization.
* Has 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 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 prior to treatment randomization.

Exclusion Criteria:

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

* Has a diagnosis of small cell lung cancer or, for mixed tumors, presence of small cell elements.
* Participants with squamous histology are excluded if there is a known tumor-activating epidermal growth factor receptor (EGFR) mutation or anaplastic lymphoma kinase (ALK) or c ros oncogene 1 (ROS1) gene rearrangement.
* Is HIV-infected with a history of Kaposi's sarcoma and/or Multicentric Castleman's Disease
* Clinically severe pulmonary compromise resulting from intercurrent pulmonary illnesses including, but not limited to, any underlying pulmonary disorder, or any autoimmune, connective tissue, or inflammatory disorders with pulmonary involvement.
* Has evidence of any leptomeningeal disease.
* Has known history of, or active, neurologic paraneoplastic syndrome.
* Has clinically significant corneal disease.
* Has myocardial infarction within 6 months.
* Has New York Heart Association (NYHA) Classes 3 or 4 congestive heart failure.
* Has uncontrolled angina pectoris within 6 months.
* Has cardiac arrhythmia requiring ongoing antiarrhythmic treatment.
* Has history of clinically relevant ventricular arrhythmias, such as ventricular tachycardia, ventricular fibrillation, or Torsade de Pointes.
* Has bradycardia of less than 50 beats per minute (bpm) unless the participant has a pacemaker.
* Has history of second- or third-degree heart block. Candidates with a history of heart block may be eligible if they currently have pacemakers and have no history of fainting or clinically relevant arrhythmia with pacemakers.
* Has coronary/peripheral artery bypass graft within 6 months.
* Has complete left bundle branch block.
* Has inadequate washout period from prior concomitant therapy as specified in protocol before randomization.
* Has received prior treatment with a topoisomerase I inhibitor or an anti-HER3 antibody and/or ADC that consists of an exatecan derivative that is a topoisomerase I inhibitor.
* 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 protein (anti-PD-L1), or anti- programmed cell death ligand 2 protein (anti-PD-L2) agent, or with an agent directed to another stimulatory or coinhibitory T-cell receptor.
* Has received prior radiotherapy within 2 weeks of randomization, has radiation related toxicity requiring corticosteroids, or has had radiation pneumonitis.
* 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.
* Has diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy 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 to any of the study interventions and/or any of their excipients.
* Has active autoimmune disease that has required systemic treatment in the past 2 years.
* Has active infection requiring systemic therapy.
* Has concurrent active Hepatitis B and Hepatitis C virus infection.
* Have not adequately recovered from major surgery or have ongoing surgical complications.

Where this trial is running

Lexington, Kentucky and 40 other locations

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 CancerLung NeoplasmsLung CancerPulmonary NeoplasmsPulmonary CancerNon-Small Cell Lung Carcinoma
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.