A Study of Pembrolizumab With or Without Chemotherapy in Combination With Additional Treatments for Advanced Non-Small Cell Lung Cancer (NSCLC) (MK-3475-01G/KEYMAKER U01)

The film gives the main points. The full list below is copied from the registry; the study team makes the final decision.

• Age18 Years to no maximum
• SexAll
• Healthy volunteersNo

You may be able to join if

• 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.

You cannot join if

• 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.

This is how the treatment is meant to work. Whether it helps, and how safe it is, is what this trial is testing.

pembrolizumab. A humanized monoclonal immunoglobulin (Ig) G4 antibody directed against human cell surface receptor PD-1 (programmed death-1 or programmed cell death-1) with potential immune checkpoint inhibitory and antineoplastic activities. Upon administration, pembrolizumab binds to PD-1, an inhibitory signaling receptor expressed on the surface of activated T cells, and blocks the binding to and activation of PD-1 by its ligands, which results in the activation of T-cell-mediated immune responses against tumor cells. The ligands for PD-1 include programmed cell death ligand 1 (PD-L1), overexpressed on certain cancer cells, and programmed cell death ligand 2 (PD-L2), which is primarily expressed on APCs. Activated PD-1 negatively regulates T-cell activation and plays a key role in in tumor evasion from host immunity. NCI Drug Dictionary

patritumab deruxtecan. An antibody-drug conjugate (ADC) composed of patritumab, a monoclonal antibody directed against the human epidermal growth factor receptor HER3 (ErbB3),linked to the topoisomerase I inhibitor DX 8951, a semisynthetic, water-soluble derivative of camptothecin, with potential antineoplastic activity. Upon administration of patritumab deruxtecan, the patritumab moiety targets and binds to HER3. After internalization, DX 8951 inhibits topoisomerase I activity by stabilizing the complex between topoisomerase I and DNA and inhibiting religation of DNA breaks, thereby inhibiting DNA replication and triggering apoptotic cell death. HER3, a member of the epidermal growth factor receptor (EGFR) family of receptor tyrosine kinases, is frequently overexpressed in tumors. NCI Drug Dictionary

Treatments listed in the registry

• Pembrolizumab (Biological): Pembrolizumab 200mg IV Infusion.
• Carboplatin (Drug): Carboplatin IV infusion AUC5 or 6 mg/mL•min and not exceeding 900mg.
• Paclitaxel (Drug): Paclitaxel 200 mg/m^2 IV infusion.
• Nab-paclitaxel (Drug): Nab-paclitaxel 100mg/m^2 IV infusion.
• Pemetrexed (Drug): Pemetrexed 500mg/m^2 IV infusion.
• HER3-DXd (Biological): HER3-Dxd 5.6mg/kg IV infusion.

Randomized · Parallel · masking: Single

Main goals

• Overall Response Rate (ORR) (Up to ~ 5 years)
• Number of Participants with Adverse Events (AEs) (Up to ~ 5 years)
• Number of Participants Discontinuing Study Drug Due to AEs (Up to ~ 2 years)

Other goals

• Duration of Response (DOR)
• Progression-free Survival (PFS)
• Overall Survival (OS)

Planned enrollment: 90 (estimated).

• University of Kentucky ( Site 0019), Lexington, Kentucky
• MedStar Franklin Square Medical Center ( Site 0033), Baltimore, Maryland
• Sanford Fargo Medical Center ( Site 0039), Fargo, North Dakota
• Abramson Cancer Center ( Site 0010), Philadelphia, Pennsylvania
• Sanford Cancer Center ( Site 0038), Sioux Falls, South Dakota

32 recruiting sites outside the US. Site status as of Oct 30, 2026. Check the live record before contacting a site.

• ClinicalTrials.gov NCT06731907
• NCI Drug Dictionary: C106432
• NCI Drug Dictionary: C136987

Registry record reviewed as fetched Oct 30, 2026, last updated by the sponsor Oct 15, 2026. Public record; not medical advice.