RECRUITING Phase 2 ClinicalTrials.gov

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)

Sponsor: Merck Sharp & Dohme LLC • ClinicalTrials.gov ID: NCT06731907

Registry updated: 2026-10-16

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Description

Researchers are investigating new treatments for untreated advanced non-small cell lung cancer (NSCLC), which is the most common form of lung cancer and lung cancer that has spread beyond surgical removal. Standard treatments include immunotherapy, such as pembrolizumab, and chemotherapy. This study aims to determine the effectiveness of adding other treatments, including the human epidermal growth factor receptor 3-directed antibody-drug conjugate (HER3-DXd) patritumab deruxtecan, to pembrolizumab, with or without chemotherapy. The primary goals are to assess safety and efficacy of the treatments.

Interventions

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.

Eligibility 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.

Conditions

Non-small Cell Lung Cancer

Locations

University of Kentucky ( Site 0019) — Lexington, Kentucky, United States
MedStar Franklin Square Medical Center ( Site 0033) — Baltimore, Maryland, United States
Sanford Fargo Medical Center ( Site 0039) — Fargo, North Dakota, United States
Abramson Cancer Center ( Site 0010) — Philadelphia, Pennsylvania, United States
Sanford Cancer Center ( Site 0038) — Sioux Falls, South Dakota, United States
Centro de Estudios Clínicos SAGA ( Site 0162) — Santiago, Region M. de Santiago, Chile
Fundación Arturo López Pérez ( Site 0161) — Santiago, Region M. de Santiago, Chile
Bradfordhill ( Site 0160) — Santiago, Region M. de Santiago, Chile
THORACIC GENERAL HOSPITAL OF ATHENS "I SOTIRIA"-3rd Dept of Internal Medicine and Laboratory, Oncol ( Site 0204) — Athens, Attica, Greece
European Interbalkan Medical Center-Oncology Department ( Site 0205) — Thessaloniki, Greece
Petz Aladar Egyetemi Oktato Korhaz ( Site 0062) — Győr, Győr-Moson-Sopron, Hungary
Jasz-Nagykun-Szolnok Varmegyei Hetenyi Geza Korhaz-Rendelointezet ( Site 0061) — Szolnok, Jász-Nagykun-Szolnok, Hungary
Országos Korányi Pulmonológiai Intézet ( Site 0060) — Budapest, Hungary
Rambam Health Care Campus ( Site 0076) — Haifa, Israel
Shaare Zedek Medical Center ( Site 0075) — Jerusalem, Israel
Meir Medical Center ( Site 0071) — Kfar Saba, Israel
Rabin Medical Center ( Site 0074) — Petah Tikva, Israel
Sheba Medical Center ( Site 0070) — Ramat Gan, Israel
Sourasky Medical Center ( Site 0077) — Tel Aviv, Israel
Fondazione IRCCS Istituto Nazionale dei Tumori ( Site 0175) — Milan, Lombardy, Italy
IRCCS Ospedale San Raffaele ( Site 0171) — Milan, Italy
Fondazione Policlinico Universitario Agostino Gemelli IRCCS - Università Cattolica del Sacro Cuore ( Site 0174) — Roma, Italy
Wielkopolskie Centrum Pulmonologii i Torakochirurgii-Oddzial Onkologii Klinicznej z Pododdzialem Dz ( Site 0153) — Poznan, Greater Poland Voivodeship, Poland
Narodowy Instytut Onkologii im. Marii Sklodowskiej-Curie - Panstwowy Instytut Badawczy w Warszawie ( Site 0151) — Warsaw, Masovian Voivodeship, Poland
Uniwersyteckie Centrum Kliniczne-Early Clinical Trials Unit ( Site 0150) — Gdansk, Pomeranian Voivodeship, Poland
Szpital Wojewódzki im. Mikoaja Kopernika w Koszalinie-Oddzial Dzienny Chemioterapii ( Site 0152) — Koszalin, West Pomeranian Voivodeship, Poland
Institut Català d'Oncologia - L'Hospitalet ( Site 0090) — L'Hospitalet de Llobregat, Barcelona, Spain
Hospital Clinic de Barcelona ( Site 0092) — Barcelona, Spain
Hospital Universitario Quiron Madrid ( Site 0091) — Madrid, Spain
Changhua Christian Hospital ( Site 0181) — Changhua, Taiwan
Taipei Medical University Hospital ( Site 0180) — Taipei, Taiwan
Chang Gung Medical Foundation-Linkou Branch ( Site 0182) — Taoyuan, Taiwan
Baskent University Dr. Turgut Noyan Research and Training Center ( Site 0141) — Adana, Turkey (Türkiye)
Hacettepe Universite Hastaneleri ( Site 0140) — Ankara, Turkey (Türkiye)
Ankara Bilkent Şehir Hastanesi ( Site 0142) — Ankara, Turkey (Türkiye)
CNE CC of Oncology Hematol ( Site 0130) — Cherkasy, Cherkasy Oblast, Ukraine
Municipal Enterprise "Bukovinian сlinical oncology сenter" ( Site 0136) — Chernivtsi, Chernivetska Oblast, Ukraine
CNCE Precarpathian Clinical Oncologic Center ( Site 0131) — Ivano-Frankivsk, Ivano-Frankivsk Oblast, Ukraine
VISION PARTNER Medical Centre ( Site 0134) — Kyiv, Kyivska Oblast, Ukraine
Communal Noncommercial Enterprise "Podillia Regional Oncology Center Of Vinnytsia Regional Council" ( Site 0133) — Vinnytsia, Vinnytsia Oblast, Ukraine
Shalimov Institute of Surgery and Transplantation ( Site 0135) — Kyiv, Ukraine

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Data sourced from ClinicalTrials.gov, a service of the U.S. National Institutes of Health.

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