KEYMAKER-U01 Substudy 01A: Efficacy and Safety Study of Pembrolizumab (MK-3475) With or Without Chemotherapy When Used With Investigational Agents in Treatment-naïve Participants With Stage IV Non-small Cell Lung Cancer (NSCLC) (MK-3475-01A/KEYMAKER-U01A)
NCT ID: NCT04165070
Last Updated: 2025-11-10
Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
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RECRUITING
PHASE1/PHASE2
450 participants
INTERVENTIONAL
2019-12-19
2032-02-13
Brief Summary
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This study is one of the pembrolizumab substudies being conducted under one pembrolizumab umbrella master protocol (MK-3475-U01/KEYMAKER-U01).
Detailed Description
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Conditions
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Keywords
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Study Design
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RANDOMIZED
PARALLEL
TREATMENT
NONE
Study Groups
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Part A: Pembrolizumab+Vibostolimab+Carboplatin + Paclitaxel
On Day 1 of each 3-week cycle, participants with squamous NSCLC receive pembrolizumab 200 mg intravenously (IV) PLUS vibostolimab IV PLUS carboplatin Area Under the Concentration-Time Curve (AUC) 6 IV PLUS paclitaxel 200 mg/m\^2 IV in Cycles 1-4, followed by maintenance treatment of pembrolizumab 200 mg IV PLUS vibostolimab IV in Cycles 5-35 (total treatment duration: up to approximately 2 years).
Pembrolizumab
IV infusion
Carboplatin
IV infusion
Paclitaxel
IV infusion
Vibostolimab
IV infusion
Part A: Pembrolizumab+Vibostolimab+Carboplatin + Pemetrexed
On Day 1 of each 3-week cycle, participants with nonsquamous NSCLC receive pembrolizumab 200 mg IV PLUS vibostolimab IV PLUS carboplatin AUC 5 IV PLUS pemetrexed 500 mg/m\^2 IV in Cycles 1-4, followed by maintenance treatment of pembrolizumab 200 mg IV PLUS vibostolimab IV PLUS pemetrexed 500 mg/m\^2 IV in Cycles 5-35 (total treatment duration: up to approximately 2 years).
Pembrolizumab
IV infusion
Carboplatin
IV infusion
Pemetrexed
IV infusion
Vibostolimab
IV infusion
Part A: Pembrolizumab+Boserolimab+Carboplatin+Paclitaxel
On Day 1 of each 3-week cycle, participants with squamous NSCLC receive pembrolizumab 200 mg IV PLUS carboplatin AUC 6 IV PLUS paclitaxel 200 mg/m\^2 IV PLUS boserolimab IV on Day 1 every 6 weeks (every other 3-week cycle) (Q6W) in Cycles 1-4, followed by maintenance treatment of pembrolizumab 200 mg IV Q3W PLUS boserolimab IV Q6W from Cycles 5 up to Cycle 35 (total treatment duration: up to approximately 2 years).
Pembrolizumab
IV infusion
Carboplatin
IV infusion
Paclitaxel
IV infusion
Boserolimab
IV infusion
Part A: Pembrolizumab+Boserolimab+Carboplatin+Pemetrexed
On Day 1 of each 3-week cycle, participants with nonsquamous NSCLC receive pembrolizumab 200 mg IV PLUS carboplatin AUC 5 IV PLUS pemetrexed 500 mg/m\^2 IV PLUS boserolimab IV on Day 1 every 6 weeks (every other 3-week cycle) (Q6W) in Cycles 1-4, followed by maintenance treatment of pembrolizumab 200 mg IV Q3W PLUS pemetrexed 500 mg/m\^2 IV Q3W PLUS boserolimab IV Q6W from Cycles 5 up to Cycle 35 (total treatment duration: up to approximately 2 years).
Pembrolizumab
IV infusion
Carboplatin
IV infusion
Pemetrexed
IV infusion
Boserolimab
IV infusion
Part A: Pembrolizumab+MK-4830+Carboplatin+Paclitaxel
On Day 1 of each 3-week cycle, participants with squamous NSCLC receive pembrolizumab 200 mg IV PLUS MK-4830 IV PLUS carboplatin AUC 6 IV PLUS paclitaxel 200 mg/m\^2 IV in Cycles 1-4, followed by maintenance treatment of pembrolizumab 200 mg IV PLUS MK-4830 IV in Cycles 5-35 (total treatment duration: up to approximately 2 years).
Pembrolizumab
IV infusion
Carboplatin
IV infusion
Paclitaxel
IV infusion
MK-4830
IV infusion
Part A: Pembrolizumab+MK-4830+Carboplatin+Pemetrexed
On Day 1 of each 3-week cycle, participants with nonsquamous NSCLC receive pembrolizumab 200 mg IV PLUS MK-4830 IV PLUS carboplatin AUC 5 IV PLUS pemetrexed 500 mg/m\^2 IV in Cycles 1-4, followed by maintenance treatment of pembrolizumab 200 mg IV PLUS MK-4830 IV PLUS pemetrexed 500 mg/m\^2 IV in Cycles 5-35 (total treatment duration: up to approximately 2 years).
Pembrolizumab
IV infusion
Carboplatin
IV infusion
Pemetrexed
IV infusion
MK-4830
IV infusion
Part A: Pembrolizumab+MK-0482+Carboplatin+Paclitaxel
On Day 1 of each 3-week cycle, participants with squamous NSCLC receive pembrolizumab 200 mg IV PLUS MK-0482 IV PLUS carboplatin AUC 6 IV PLUS paclitaxel 200 mg/m\^2 IV in Cycles 1-4, followed by maintenance treatment of pembrolizumab 200 mg IV PLUS MK-0482 IV in Cycles 5-35 (total treatment duration: up to approximately 2 years).
Pembrolizumab
IV infusion
Carboplatin
IV infusion
MK-0482
IV Infusion
Part A: Pembrolizumab+MK-0482+Carboplatin+Pemetrexed
On Day 1 of each 3-week cycle, participants with nonsquamous NSCLC receive pembrolizumab 200 mg IV PLUS MK-0482 IV PLUS carboplatin AUC 5 IV PLUS pemetrexed 500 mg/m\^2 IV in Cycles 1-4, followed by maintenance treatment of pembrolizumab 200 mg IV PLUS MK-0482 IV PLUS pemetrexed 500 mg/m\^2 IV in Cycles 5-35 (total treatment duration: up to approximately 2 years).
Pembrolizumab
IV infusion
Carboplatin
IV infusion
MK-0482
IV Infusion
Part B: Pembrolizumab + I-DXd
On Day 1 of each 3-week cycle, participants with squamous and nonsquamous NSCLC will receive pembrolizumab 200 mg IV for up to 2 years, PLUS I-DXd in escalating doses until progressive disease or toxicity.
Pembrolizumab
IV infusion
Ifinatamab Deruxtecan (I-DXd)
IV infusion
Part B: Pembrolizumab + Carboplatin + I-DXd
On Day 1 of each 3-week cycle, participants will receive pembrolizumab 200 mg IV for up to 2 years, PLUS carboplatin AUC 5-6 up to 4 cycles PLUS I-DXd IV in escalating doses until PD or toxicity.
Pembrolizumab
IV infusion
Carboplatin
IV infusion
Ifinatamab Deruxtecan (I-DXd)
IV infusion
Part B: Pembrolizumab + Carboplatin + HER3-DXd
On Day 1 of each 3-week cycle, participants will receive pembrolizumab 200 mg IV for up to 2 years, PLUS carboplatin AUC 5-6 up to 4 cycles PLUS HER3-DXd IV in escalating doses until PD or toxicity.
Pembrolizumab
IV infusion
Carboplatin
IV infusion
HER3-DXd
IV Infusion
Interventions
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Pembrolizumab
IV infusion
Carboplatin
IV infusion
Paclitaxel
IV infusion
Pemetrexed
IV infusion
Vibostolimab
IV infusion
Boserolimab
IV infusion
MK-4830
IV infusion
MK-0482
IV Infusion
Ifinatamab Deruxtecan (I-DXd)
IV infusion
HER3-DXd
IV Infusion
Other Intervention Names
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Eligibility Criteria
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Inclusion Criteria
* Participants with nonsquamous NSCLC who are not eligible for an approved targeted therapy
* Is able to provide archival tumor tissue sample collected either within 5 years or within the interval from completion of last treatment but before entering the screening period or newly obtained core or excisional biopsy of a tumor lesion not previously irradiated obtained within 90 days of treatment initiation
* Has not received prior systemic treatment for their metastatic NSCLC
* Is able to complete all screening procedures within the 35-day screening window for Part A and 28-day screening window for Part B
Exclusion Criteria
* Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days before the first dose of study treatment
* Has a known additional malignancy that is progressing or has required active treatment within the past 2 years
* Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis
* Has an active autoimmune disease that has required systemic treatment in the past 2 years
* Has a history of (noninfectious) pneumonitis that required steroids or has current pneumonitis
* Has an active infection requiring systemic therapy
* Has clinically significant cardiac disease, including unstable angina, acute myocardial infarction within 6 months from Day 1 of study treatment administration, or New York Heart Association Class III or IV congestive heart failure
* Has a known history of human immunodeficiency virus (HIV) infection. Well-controlled HIV with anti-retroviral therapy (ART) is not excluded
* Has a known history of Hepatitis B (HPV) or known active Hepatitis C virus infection. Hepatitis B surface antigen (HBsAg) positive is eligible if on HBV antiviral therapy for at least 4 weeks and HBV viral load is undetectable prior to randomization
* Has had major surgery \<3 weeks before the first dose of study treatment
* Is expected to require any other form of antineoplastic therapy while on study
* Has a history or current evidence of a gastrointestinal (GI) condition (e.g. inflammatory bowel disease, Crohn's disease, ulcerative colitis) or impaired liver function or diseases that in the opinion of the investigator may significantly alter the absorption or metabolism of oral medications
* Is getting chemotherapy and has clinically active diverticulitis, intra-abdominal abscess, GI obstruction, or peritoneal carcinomatosis
* Has preexisting neuropathy that is moderate in intensity
* Has received prior systemic cytotoxic chemotherapy or other targeted or biological antineoplastic therapy for metastatic disease
* Is unable or unwilling to take folic acid or vitamin B12 supplementation, for participants who will receive pemetrexed
* Has a known sensitivity to any component of carboplatin, paclitaxel, pemetrexed or any of their excipients
* Has received prior radiation therapy to the lung that is \>30 Gray (Gy) within 6 months of the first dose of study treatment
* Has received a live vaccine within 30 days before the first dose of study treatment. Any licensed COVID-19 vaccine (including for Emergency Use) in a particular country is allowed as long as they are messenger ribonucleic acid (mRNA) vaccines, adenoviral vaccines, or inactivated vaccines. Investigational vaccines (ie, those not licensed or approved for Emergency Use) are not allowed
* Has received any prior immunotherapy and was discontinued from that treatment due to a severe or worse immune-related adverse event (irAE)
* Has had chemotherapy or biological cancer therapy within 4 weeks before the first dose of study treatment or has not recovered to Common Terminology Criteria for Adverse Events (CTCAE) Grade 1 or better from the AEs due to cancer therapeutics administered more than 4 weeks before the first dose of study treatment (including participants who had previous immunomodulatory therapy with residual irAEs)
* Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks before the first dose of study treatment
* Previously had a severe hypersensitivity reaction to treatment with monoclonal antibodies (including pembrolizumab) and/or any of their excipients
* Has had an allogenic tissue/solid organ transplant
18 Years
ALL
No
Sponsors
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Daiichi Sankyo
INDUSTRY
Merck Sharp & Dohme LLC
INDUSTRY
Responsible Party
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Principal Investigators
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Medical Director
Role: STUDY_DIRECTOR
Merck Sharp & Dohme LLC
Locations
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Banner MD Anderson Cancer Center ( Site 0001)
Gilbert, Arizona, United States
City of Hope ( Site 0014)
Duarte, California, United States
UCSF Medical Center at Mission Bay ( Site 0007)
San Francisco, California, United States
Georgetown University ( Site 0036)
Washington D.C., District of Columbia, United States
University of Kentucky Markey Cancer Center ( Site 0019)
Lexington, Kentucky, United States
MedStar Franklin Square Medical Center ( Site 0033)
Baltimore, Maryland, United States
Massachusetts General Hospital ( Site 0003)
Boston, Massachusetts, United States
Dana Farber Cancer Institute ( Site 0002)
Boston, Massachusetts, United States
Oncology Hematology West, PC DBA Nebraska Cancer Specialists ( Site 0031)
Omaha, Nebraska, United States
Dartmouth Hitchcock Medical Center ( Site 0016)
Lebanon, New Hampshire, United States
John Theurer Cancer Center at Hackensack University Medical Center ( Site 0037)
Hackensack, New Jersey, United States
Laura and Isaac Perlmutter Cancer Center ( Site 0034)
New York, New York, United States
Sanford Fargo Medical Center ( Site 0039)
Fargo, North Dakota, United States
Cleveland Clinic Main ( Site 0006)
Cleveland, Ohio, United States
Abramson Cancer Center of the University of Pennsylvania ( Site 0010)
Philadelphia, Pennsylvania, United States
Sanford Cancer Center ( Site 0038)
Sioux Falls, South Dakota, United States
The University of Texas MD Anderson Cancer Center ( Site 0009)
Houston, Texas, United States
Petz Aladar Megyei Oktato Korhaz ( Site 0062)
Győr, Győr-Moson-Sopron, Hungary
Jász-Nagykun-Szolnok Vármegyei Hetényi Géza Kórház ( Site 0061)
Szolnok, Jász-Nagykun-Szolnok, Hungary
Orszagos Koranyi Pulmonologiai Intezet ( Site 0060)
Budapest, , Hungary
Soroka Medical Center ( Site 0072)
Beersheba, , Israel
Rambam Health Care Campus-Oncology ( 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
Chaim Sheba Medical Center ( Site 0070)
Ramat Gan, , Israel
Sourasky Medical Center ( Site 0077)
Tel Aviv, , Israel
Azienda Ospedaliera Universitaria Careggi ( Site 0173)
Florence, Firenze, Italy
IRCCS Ospedale San Raffaele ( Site 0171)
Milan, , Italy
Policlinico Gemelli di Roma ( Site 0174)
Roma, , Italy
Narodowy Instytut Onkologii im. Marii Sklodowskiej-Curie - P-Klinika Nowotworow Pluca i Klatki Pier ( 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
Seoul National University Bundang Hospital ( Site 0081)
Seongnam-si, Kyonggi-do, South Korea
Severance Hospital ( Site 0080)
Seoul, , South Korea
Samsung Medical Center ( Site 0082)
Seoul, , South Korea
ICO L Hospitalet ( Site 0090)
L'Hospitalet de Llobregat, Barcelona, Spain
Hospital Universitario Quiron Madrid ( Site 0091)
Madrid, , Spain
Countries
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Central Contacts
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Facility Contacts
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Study Coordinator
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Study Coordinator
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Study Coordinator
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Study Coordinator
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Study Coordinator
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Study Coordinator
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Study Coordinator
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Study Coordinator
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Related Links
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Merck Clinical Trials Information
Plain Language Summary
Other Identifiers
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MK-3475-01A
Identifier Type: OTHER
Identifier Source: secondary_id
KEYMAKER-U01A
Identifier Type: OTHER
Identifier Source: secondary_id
2023-506932-33-00
Identifier Type: REGISTRY
Identifier Source: secondary_id
U1111-1294-6474
Identifier Type: REGISTRY
Identifier Source: secondary_id
2020-001626-56
Identifier Type: EUDRACT_NUMBER
Identifier Source: secondary_id
3475-01A
Identifier Type: -
Identifier Source: org_study_id