Actively Recruiting
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)
Led by Merck Sharp & Dohme LLC · Updated on 2026-02-18
90
Participants Needed
41
Research Sites
362 weeks
Total Duration
On this page
Sponsors
M
Merck Sharp & Dohme LLC
Lead Sponsor
D
Daiichi Sankyo
Collaborating Sponsor
AI-Summary
What this Trial Is About
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.
CONDITIONS
Official Title
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)
Who Can Participate
Eligibility Criteria
You may qualify if you...
- Histologically or cytologically confirmed diagnosis of Stage IV squamous or non-squamous non-small cell lung cancer (NSCLC) per AJCC Staging Manual Version 8
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 within 7 days before randomization
- Archival tumor tissue sample or newly obtained biopsy of a tumor lesion not previously irradiated provided
- HIV-infected participants must have well controlled HIV on antiretroviral therapy
- Hepatitis B surface antigen positive participants eligible if they have received antiviral therapy for at least 4 weeks and have undetectable viral load prior to treatment
You will not qualify if you...
- Diagnosis of small cell lung cancer or presence of small cell elements in mixed tumors
- Squamous histology with known tumor-activating EGFR mutation or ALK or ROS1 gene rearrangement
- HIV infection with history of Kaposi's sarcoma and/or Multicentric Castleman's Disease
- Severe pulmonary compromise from other lung illnesses or autoimmune/connective tissue disorders with lung involvement
- Evidence of leptomeningeal disease
- Known history of or active neurologic paraneoplastic syndrome
- Clinically significant corneal disease
- Myocardial infarction within 6 months
- New York Heart Association Class 3 or 4 congestive heart failure
- Uncontrolled angina pectoris within 6 months
- Cardiac arrhythmia requiring ongoing antiarrhythmic treatment
- History of clinically relevant ventricular arrhythmias
- Bradycardia less than 50 bpm unless pacemaker present
- History of second- or third-degree heart block without pacemaker or with history of fainting or arrhythmia
- Coronary/peripheral artery bypass graft within 6 months
- Complete left bundle branch block
- Inadequate washout period from prior therapy before randomization
- Prior treatment with topoisomerase I inhibitors or anti-HER3 antibodies/ADCs
- Prior systemic anticancer therapy for metastatic NSCLC
- Prior therapy with anti-PD-1, anti-PD-L1, anti-PD-L2, or other T-cell receptor agents
- Radiotherapy within 2 weeks before randomization or radiation-related toxicity requiring corticosteroids
- Radiation therapy to lung >30 gray within 6 months before study start
- Live or live-attenuated vaccine within 30 days before first dose
- Immunodeficiency or chronic systemic steroid or immunosuppressive therapy within 7 days before first dose
- Active malignancy progressing or requiring treatment within past 3 years
- Active central nervous system metastases or carcinomatous meningitis
- Severe hypersensitivity to study treatments or excipients
- Active autoimmune disease requiring systemic treatment in past 2 years
- Active infection requiring systemic therapy
- Concurrent active Hepatitis B and C infection
- Incomplete recovery from major surgery or ongoing surgical complications
AI-Screening
AI-Powered Screening
Complete this quick 3-step screening to check your eligibility
Trial Site Locations
Total: 41 locations
1
University of Kentucky ( Site 0019)
Lexington, Kentucky, United States, 40536
Actively Recruiting
2
MedStar Franklin Square Medical Center ( Site 0033)
Baltimore, Maryland, United States, 21237
Actively Recruiting
3
Sanford Fargo Medical Center ( Site 0039)
Fargo, North Dakota, United States, 58102
Actively Recruiting
4
Abramson Cancer Center ( Site 0010)
Philadelphia, Pennsylvania, United States, 19104
Actively Recruiting
5
Sanford Cancer Center ( Site 0038)
Sioux Falls, South Dakota, United States, 57104
Actively Recruiting
6
Centro de Estudios Clínicos SAGA ( Site 0162)
Santiago, Region M. de Santiago, Chile, 7500653
Actively Recruiting
7
FALP ( Site 0161)
Santiago, Region M. de Santiago, Chile, 7500921
Actively Recruiting
8
Bradfordhill ( Site 0160)
Santiago, Region M. de Santiago, Chile, 8420383
Actively Recruiting
9
THORACIC GENERAL HOSPITAL OF ATHENS "I SOTIRIA"-3rd Dept of Internal Medicine and Laboratory, Oncol ( Site 0204)
Athens, Attica, Greece, 115 27
Actively Recruiting
10
European Interbalkan Medical Center-Oncology Department ( Site 0205)
Thessaloniki, Greece, 570 01
Actively Recruiting
11
Petz Aladar Egyetemi Oktato Korhaz ( Site 0062)
Győr, Győr-Moson-Sopron, Hungary, 9024
Actively Recruiting
12
Jasz-Nagykun-Szolnok Megyei Hetenyi Gyula Korhaz-Rendelointezet ( Site 0061)
Szolnok, Jász-Nagykun-Szolnok, Hungary, 5000
Actively Recruiting
13
Országos Korányi Pulmonológiai Intézet ( Site 0060)
Budapest, Hungary, 1121
Actively Recruiting
14
Rambam Health Care Campus ( Site 0076)
Haifa, Israel, 3109601
Actively Recruiting
15
Shaare Zedek Medical Center ( Site 0075)
Jerusalem, Israel, 9103102
Actively Recruiting
16
Meir Medical Center ( Site 0071)
Kfar Saba, Israel, 4428164
Actively Recruiting
17
Rabin Medical Center ( Site 0074)
Petah Tikva, Israel, 4941492
Actively Recruiting
18
Sheba Medical Center ( Site 0070)
Ramat Gan, Israel, 5262000
Actively Recruiting
19
Sourasky Medical Center ( Site 0077)
Tel Aviv, Israel, 6423906
Actively Recruiting
20
Fondazione IRCCS Istituto Nazionale dei Tumori ( Site 0175)
Milan, Lombardy, Italy, 20133
Actively Recruiting
21
IRCCS Ospedale San Raffaele ( Site 0171)
Milan, Italy, 20132
Actively Recruiting
22
Fondazione Policlinico Universitario Agostino Gemelli IRCCS - Università Cattolica del Sacro Cuore ( Site 0174)
Roma, Italy, 00168
Actively Recruiting
23
Wielkopolskie Centrum Pulmonologii i Torakochirurgii-Oddzial Onkologii Klinicznej z Pododdzialem Dz ( Site 0153)
Poznan, Greater Poland Voivodeship, Poland, 60-569
Actively Recruiting
24
Narodowy Instytut Onkologii im. Marii Sklodowskiej-Curie - Panstwowy Instytut Badawczy w Warszawie ( Site 0151)
Warsaw, Masovian Voivodeship, Poland, 02-781
Actively Recruiting
25
Uniwersyteckie Centrum Kliniczne-Early Clinical Trials Unit ( Site 0150)
Gdansk, Pomeranian Voivodeship, Poland, 80-214
Actively Recruiting
26
Szpital Wojewódzki im. Mikoaja Kopernika w Koszalinie-Oddzial Dzienny Chemioterapii ( Site 0152)
Koszalin, West Pomeranian Voivodeship, Poland, 75-581
Actively Recruiting
27
Institut Català d'Oncologia - L'Hospitalet ( Site 0090)
L'Hospitalet de Llobregat, Barcelona, Spain, 08908
Actively Recruiting
28
HOSPITAL CLÍNIC DE BARCELONA ( Site 0092)
Barcelona, Spain, 08008
Actively Recruiting
29
Hospital Universitario Quiron Madrid ( Site 0091)
Madrid, Spain, 28223
Actively Recruiting
30
Changhua Christian Hospital ( Site 0181)
Changhua, Taiwan, 50006
Actively Recruiting
31
Taipei Medical University Hospital ( Site 0180)
Taipei, Taiwan, 110
Actively Recruiting
32
Chang Gung Medical Foundation-Linkou Branch ( Site 0182)
Taoyuan, Taiwan, 33305
Actively Recruiting
33
Baskent University Dr. Turgut Noyan Research and Training Center ( Site 0141)
Adana, Turkey (Türkiye), 01250
Active, Not Recruiting
34
Hacettepe Universite Hastaneleri ( Site 0140)
Ankara, Turkey (Türkiye), 06410
Actively Recruiting
35
Ankara Bilkent Şehir Hastanesi ( Site 0142)
Ankara, Turkey (Türkiye), 06530
Actively Recruiting
36
CNE CC of Oncology Hematol ( Site 0130)
Cherkasy, Cherkasy Oblast, Ukraine, 18009
Active, Not Recruiting
37
Municipal Enterprise "Bukovinian сlinical oncology сenter" ( Site 0136)
Chernivtsi, Chernivetska Oblast, Ukraine, 58013
Actively Recruiting
38
CNCE Precarpathian Clinical Oncologic Center ( Site 0131)
Ivano-Frankivsk, Ivano-Frankivsk Oblast, Ukraine, 76018
Actively Recruiting
39
VISION PARTNER Medical Centre ( Site 0134)
Kyiv, Kyivska Oblast, Ukraine, 03022
Active, Not Recruiting
40
Communal Noncommercial Enterprise "Podillia Regional Oncology Center Of Vinnytsia Regional Council" ( Site 0133)
Vinnytsia, Vinnytsia Oblast, Ukraine, 21029
Actively Recruiting
41
Shalimov Institute of Surgery and Transplantation ( Site 0135)
Kyiv, Ukraine, 03126
Actively Recruiting
Research Team
T
Toll Free Number
CONTACT
How is the study designed?
Study Type
INTERVENTIONAL
Masking
SINGLE
Allocation
RANDOMIZED
Model
PARALLEL
Primary Purpose
TREATMENT
Number of Arms
2
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