Study of Pembrolizumab (MK-3475) Subcutaneous (SC) Versus Pembrolizumab Intravenous (IV) Administered With Platinum Doublet Chemotherapy in Participants With Metastatic Squamous or Nonsquamous Non-Small Cell Lung Cancer (NSCLC) (MK-3475-A86)

A Randomized, Phase 3, Open-label Study to Investigate the Pharmacokinetics and Safety of Subcutaneous Pembrolizumab Versus Intravenous Pembrolizumab, Administered With Platinum Doublet Chemotherapy, in the First-Line Treatment of Participants With Metastatic Squamous or Nonsquamous Non-Small-Cell Lung Cancer

The purpose of this study is to evaluate pembrolizumab (MK-3475) subcutaneous (SC) administration as the first-line therapy in the treatment of metastatic squamous and nonsquamous NSCLC by assessing the pharmacokinetics (PK), safety, and efficacy of pembrolizumab SC injection in combination with standard-of-care chemotherapy. The primary hypothesis of the study is Pembrolizumab SC is noninferior to pembrolizumab intravenous (IV) for Cycle 1 Area Under Curve (AUC) and Cycle 6 minimal concentration (Ctrough) at steady state.

Participants who discontinue study treatment after receiving the first course of 35 administrations of pembrolizumab (approximately up to 2 years) for reasons other than disease progression or intolerability, may be eligible for a second course of pembrolizumab for up to approximately 1 additional year if they have experienced radiographic disease progression per RECIST 1.1 as assessed by BICR after stopping first course treatment.

Study Overview

• Status: Active, not recruiting
• Conditions: Non-Small Cell Lung Cancer
• Intervention / Treatment: Drug: Carboplatin; Drug: Pemetrexed; Drug: Cisplatin; Biological: Pembrolizumab SC; Drug: Paclitaxel; Drug: Nab-Paclitaxel; Biological: Pembrolizumab IV

• Study Type: Interventional
• Enrollment (Actual): 531
• Phase: Phase 3

Contacts and Locations

Study Locations

• Brazil
  • Espirito Santo
    • Cachoeiro de Itapemirim, Espirito Santo, Brazil, 29308-065
      • HOSPITAL EVANGÉLICO DE CACHOEIRO DE ITAPEMIRIM ( Site 0307)
  • Rio Grande Do Sul
    • Passo Fundo, Rio Grande Do Sul, Brazil, 99010-080
      • Hospital Sao Vicente de Paulo ( Site 0311)
  • Santa Catarina
    • Joinville, Santa Catarina, Brazil, 89201260
      • Instituto Joinvilense de Hematologia e Oncologia ( Site 0308)
  • Sao Paulo
    • Sao Jose do Rio Preto, Sao Paulo, Brazil, 15090-000
      • Fundacao Faculdade Regional de Medicina de Sao Jose do Rio Preto ( Site 0305)
    • São Paulo, Sao Paulo, Brazil, 04014-002
      • Núcleo de Pesquisa Clínica da Rede São Camilo ( Site 0304)
• France
  • Paris, France, 75014
    • Hopital Cochin ( Site 1002)
  • Bas-Rhin
    • Strasbourg, Bas-Rhin, France, 67091
      • Nouvel Hôpital Civil (NHC) ( Site 1018)
  • Haute-Vienne
    • Limoges, Haute-Vienne, France, 87042
      • CHU Limoges CHU Dupuytren ( Site 1011)
  • Hauts-de-Seine
    • Suresnes, Hauts-de-Seine, France, 92150
      • Hôpital Foch ( Site 1019)
  • Herault
    • Montpellier, Herault, France, 34298
      • Institut Regional du Cancer de Montpellier - ICM ( Site 1003)
  • La Reunion
    • Saint-Pierre, La Reunion, France, 97448
      • Centre Hospitalier Sud Réunion ( Site 1020)
  • Loire-Atlantique
    • Saint-Herblain, Loire-Atlantique, France, 44800
      • Hopital Guillaume & Rene Laennec ( Site 1007)
  • Pyrenees-Atlantiques
    • Pau, Pyrenees-Atlantiques, France, 64000
      • Centre Hospitalier de Pau ( Site 1016)
  • Seine-Maritime
    • Rouen, Seine-Maritime, France, 76031
      • CHU de Rouen ( Site 1013)
• Guatemala
  • Guatemala, Guatemala, 01010
    • Centro de Investigaciones Clinicas de Latinoamerica S.A. - CELAN ( Site 0602)
  • Guatemala, Guatemala, 01010
    • Clinica Privada Dr. Rixci Ramirez ( Site 0601)
  • Guatemala, Guatemala, 01010
    • INTERVASC ( Site 0605)
  • Guatemala, Guatemala, 01015
    • Grupo Angeles SA ( Site 0604)
  • Quetzaltenango, Guatemala, 09001
    • Centro Regional de Sub Especialidades Médicas SA ( Site 0600)
• Hungary
  • Budapest, Hungary, 1083
    • Semmelweis University-Pulmonológiai Klinika ( Site 1114)
  • Budapest, Hungary, 1121
    • Országos Korányi Pulmonológiai Intézet ( Site 1104)
  • Bacs-Kiskun
    • Kecskemét, Bacs-Kiskun, Hungary, 6000
      • Bacs-Kiskun Megyei Korhaz-Onkoradiologiai Kozpont ( Site 1106)
  • Gyor-Moson-Sopron
    • Gyor, Gyor-Moson-Sopron, Hungary, 9023
      • Petz Aladar Megyei Oktato Korhaz ( Site 1110)
  • Jasz-Nagykun-Szolnok
    • Szolnok, Jasz-Nagykun-Szolnok, Hungary, 5000
      • Jasz Nagykun Szolnok Megyei Hetenyi Geza Korhaz Rendelointezet ( Site 1103)
  • Pest
    • Torokbalint, Pest, Hungary, 2045
      • Tudogyogyintezet Torokbalint ( Site 1105)
  • Veszprem
    • Farkasgyepu, Veszprem, Hungary, 8582
      • Veszprem Megyei Tudogyogyintezet ( Site 1108)
  • Zalaegerszeg
    • Zalagerszeg, Zalaegerszeg, Hungary, 8900
      • Zala Megyei Szent Rafael Korhaz ( Site 1111)
• Japan
  • Chiba, Japan, 260-8677
    • Chiba University Hospital ( Site 3008)
  • Fukuoka, Japan, 810-8563
    • National Hospital Organization Kyushu Medical Center ( Site 3001)
  • Fukuoka, Japan, 811-1395
    • National Hospital Organization Kyushu Cancer Center ( Site 3002)
  • Okayama, Japan, 7008558
    • Okayama University Hospital ( Site 3012)
  • Osaka, Japan, 541-8567
    • Osaka International Cancer Institute ( Site 3018)
  • Tokushima, Japan, 770-8503
    • Tokushima University Hospital ( Site 3019)
  • Tokyo, Japan, 113-8431
    • Juntendo University Hospital ( Site 3011)
  • Tokyo, Japan, 142-8666
    • Showa University Hospital ( Site 3010)
  • Aichi
    • Toyoake, Aichi, Japan, 4701192
      • Fujita Health University Hospital ( Site 3007)
  • Ehime
    • Toon, Ehime, Japan, 791-0295
      • Ehime University Hospital ( Site 3005)
  • Fukuoka
    • Kurume, Fukuoka, Japan, 830-0011
      • Kurume University Hospital ( Site 3006)
  • Hokkaido
    • Sapporo, Hokkaido, Japan, 003-0804
      • National Hospital Organization Hokkaido Cancer Center ( Site 3014)
  • Ishikawa
    • Kanazawa, Ishikawa, Japan, 920-8641
      • Kanazawa University Hospital ( Site 3004)
  • Kanagawa
    • Yokohama, Kanagawa, Japan, 236-0051
      • Kanagawa Cardiovascular and Respiratory Center ( Site 3003)
  • Miyagi
    • Natori, Miyagi, Japan, 981-1293
      • Miyagi Cancer Center ( Site 3000)
    • Sendai, Miyagi, Japan, 980-0873
      • Sendai Kousei Hospital ( Site 3015)
  • Okayama
    • Kurashiki, Okayama, Japan, 710-8602
      • Kurashiki Central Hospital ( Site 3013)
  • Osaka
    • Hirakata, Osaka, Japan, 573-1191
      • Kansai Medical University Hospital ( Site 3016)
    • Sakai, Osaka, Japan
      • National Hospital Organization Kinki-chuo Chest Medical Center ( Site 3009)
    • Takatsuki, Osaka, Japan, 569-8686
      • Osaka Medical and Pharmaceutical University Hospital ( Site 3017)
• Korea, Republic of
  • Seoul, Korea, Republic of, 08308
    • Korea University Guro Hospital ( Site 2003)
  • Chungnam
    • Daejeon, Chungnam, Korea, Republic of, 35015
      • Chungnam National University Hospital ( Site 2002)
  • Jeonranamdo
    • Hwasun, Jeonranamdo, Korea, Republic of, 58128
      • Chonnam National University Hwasun Hospital-Pulmonology ( Site 2000)
• Peru
  • Lima, Peru, 15036
    • Clinica Internacional Sede San Borja ( Site 0705)
  • Lima, Peru, 15038
    • Instituto Nacional de Enfermedades Neoplasicas ( Site 0703)
  • Lima, Peru, 15102
    • Hospital Nacional Cayetano Heredia ( Site 0700)
  • Ariqipa
    • Arequipa, Ariqipa, Peru, 04001
      • Hospital Nacional Carlos Alberto Seguin Escobedo ESSALUD ( Site 0704)
  • La Libertad
    • Trujillo, La Libertad, Peru, 13007
      • Clínica Peruano-Americana de Trujillo ( Site 0701)
  • Muni Metro De Lima
    • Lima, Muni Metro De Lima, Peru, 15036
      • Oncosalud ( Site 0706)
• Poland
  • Kujawsko-pomorskie
    • Bydgoszcz, Kujawsko-pomorskie, Poland, 85-796
      • Centrum Onkologii im prof Franciszka Lukaszczyka ( Site 1201)
  • Mazowieckie
    • Siedlce, Mazowieckie, Poland, 08-110
      • Mazowiecki Szpital Wojewódzki w Siedlcach-Siedleckie Centrum Onkologii ( Site 1206)
    • Warszawa, Mazowieckie, Poland, 02-781
      • Narodowy Instytut Onkologii im. Marii Sklodowskiej-Curie - Panstwowy Instytut Badawczy w Warszawie (
  • Slaskie
    • Bystra, Slaskie, Poland, 43-360
      • Centrum Pulmonologii i Torakochirurgii w Bystrej ( Site 1205)
  • Wielkopolskie
    • Konin, Wielkopolskie, Poland, 62-500
      • Przychodnia Lekarska KOMED ( Site 1202)
  • Zachodniopomorskie
    • Koszalin, Zachodniopomorskie, Poland, 75-581
      • Szpital Wojewodzki im. Mikolaja Kopernika ( Site 1200)
• Romania
  • Bucuresti, Romania, 022548
    • S.C.Focus Lab Plus S.R.L ( Site 1301)
  • Bucuresti, Romania, 050098
    • Spitalul Universitar de Urgenta Bucuresti ( Site 1305)
  • Cluj
    • Cluj-Napoca, Cluj, Romania, 400015
      • Cardiomed SRL Cluj-Napoca ( Site 1313)
    • Cluj-Napoca, Cluj, Romania, 400015
      • Institutul Oncologic Prof.Dr. Ion Chiricuta Cluj-Napoca ( Site 1303)
    • Comuna Floresti, Cluj, Romania, 407280
      • SC Radiotherapy Center Cluj SRL ( Site 1307)
  • Dolj
    • Craiova, Dolj, Romania, 200347
      • S.C. Centrul de Oncologie Sf. Nectarie SRL ( Site 1304)
    • Craiova, Dolj, Romania, 200385
      • Centrul de Oncologie Oncolab-Medical Oncology ( Site 1312)
  • Prahova
    • Ploiesti, Prahova, Romania, 100337
      • Spitalul Municipal Ploiesti ( Site 1308)
  • Timis
    • Timisoara, Timis, Romania, 300239
      • Policlinica Oncomed SRL ( Site 1302)
• Russian Federation
  • Sankt-Peterburg, Russian Federation, 198255
    • SPb SBHI City Clinical Oncological Dispensary ( Site 1409)
  • Sankt-Peterburg
    • Saint-Petersburg, Sankt-Peterburg, Russian Federation, 190103
      • SPBU Clinic of Advanced medical technologies n.a. N. I. Pirogov ( Site 1406)
    • Saint-Petersburg, Sankt-Peterburg, Russian Federation, 197758
      • National Medical Research Center of Oncology N.A. N.N. Petrov ( Site 1407)
    • Saint-Petersburg, Sankt-Peterburg, Russian Federation, 197758
      • Saint-Petersburg Scientific-Practical Center of Specialized Kinds of Medical Care (o) ( Site 1424)
  • Tatarstan, Respublika
    • Kazan, Tatarstan, Respublika, Russian Federation, 420029
      • Republican Clinical Oncology Dispensary-Chemotherapy #1 ( Site 1425)
• South Africa
  • Gauteng
    • Johannesburg, Gauteng, South Africa, 2193
      • Wits Clinical Research ( Site 1510)
    • Pretoria, Gauteng, South Africa, 0002
      • Steve Biko Academic Hospital ( Site 1506)
    • Pretoria, Gauteng, South Africa, 0181
      • Marry Potter Oncology Centre ( Site 1502)
    • Sandton, Gauteng, South Africa, 2196
      • Sandton Oncology Medical Group PTY LTD ( Site 1505)
    • Soweto, Gauteng, South Africa, 2013
      • Chris Hani Baragwanath Academic Hospital-Wits Clinical Research Bara ( Site 1513)
  • Limpopo
    • Durban, Limpopo, South Africa, 4001
      • The Oncology Centre ( Site 1507)
  • Western Cape
    • Kraaifontein, Western Cape, South Africa, 7570
      • Cape Town Oncology Trials Pty Ltd ( Site 1500)
• Spain
  • Barcelona, Spain, 08035
    • H.U. Vall de Hebron ( Site 1600)
  • Huelva, Spain, 21005
    • Hospital Juan Ramon Jimenez ( Site 1602)
  • Lugo, Spain, 27003
    • Hospital Universitario Lucus Augusti ( Site 1603)
  • Madrid, Spain, 28046
    • Hospital Universitario La Paz ( Site 1601)
  • Las Palmas
    • Las Palmas de Gran Canaria, Las Palmas, Spain, 35001
      • Hospital Insular de Gran Canaria-Oncology ( Site 1604)
• Taiwan
  • Changhua, Taiwan, 50006
    • Changhua Christian Hospital ( Site 2104)
  • Hsinchu, Taiwan, 300
    • National Taiwan University Hospital Hsin-Chu Branch ( Site 2103)
  • Kaohsiung, Taiwan, 807
    • Kaohsiung Medical University Chung-Ho Memorial Hospital ( Site 2107)
  • Tainan, Taiwan, 704
    • National Cheng Kung University Hospital ( Site 2105)
  • Taipei, Taiwan, 10048
    • National Taiwan University Hospital ( Site 2101)
  • Taipei, Taiwan, 11217
    • Taipei Veterans General Hospital ( Site 2106)
  • Taoyuan, Taiwan, 333
    • Chang Gung Medical Foundation-Linkou Branch ( Site 2102)
• Turkey
  • Ankara, Turkey, 06010
    • Gulhane Egitim ve Arastirma Hastanesi ( Site 1704)
  • Ankara, Turkey, 06800
    • Ankara Sehir Hastanesi ( Site 1702)
  • Istanbul, Turkey, 34722
    • TC Saglik Bakanligi Goztepe Prof. Dr. Suleyman Yalcin Sehir Hastanesi-oncology ( Site 1701)
  • Izmir, Turkey, 35040
    • Ege Universitesi Tip Fakultesi Hastanesi ( Site 1703)
  • Malatya, Turkey, 44280
    • Inonu Universitesi Turgut Ozal Tip Merkezi ( Site 1707)
• Ukraine
  • Kyiv, Ukraine, 03115
    • Kyiv City Clinical Oncology Centre ( Site 1809)
  • Kyiv, Ukraine, 03151
    • Medical Center Dobrobut Clinic ( Site 1808)
  • Dnipropetrovska Oblast
    • Kryvyi Rih, Dnipropetrovska Oblast, Ukraine, 50000
      • Medical Center Mriya Med-Service ( Site 1805)
  • Kharkivska Oblast
    • Kharkiv, Kharkivska Oblast, Ukraine, 61070
      • Communal non profit enterprise Regional Clinical Oncology Center ( Site 1806)
  • Kirovohradska Oblast
    • Kropyvnytskyi, Kirovohradska Oblast, Ukraine, 25011
      • Ukrainian Center of Tomotherapy ( Site 1807)
  • Kyivska Oblast
    • Khodosivka, Kyivska Oblast, Ukraine, 08173
      • Medical Center Asklepion LLC ( Site 1804)
  • Odeska Oblast
    • Odesa, Odeska Oblast, Ukraine, 65025
      • Municipal non-profit enterprise'Odesa Regional Clinical Hosp-Thoracic surgery department. ( Site 181
  • Poltavska Oblast
    • Kremenchuk, Poltavska Oblast, Ukraine, 39617
      • Kremenchuk Regional Oncology Center ( Site 1811)
• United States
  • Arkansas
    • Jonesboro, Arkansas, United States, 72401
      • St. Bernards Medical Center ( Site 0103)
  • California
    • Fullerton, California, United States, 92835
      • St Joseph Heritage Healthcare-Oncology ( Site 0102)
    • Los Alamitos, California, United States, 90720
      • Cancer Blood and Specialty Clinic ( Site 0105)
    • Whittier, California, United States, 90602
      • PIH Health Hematology Medical Oncology ( Site 0106)
  • Florida
    • Fort Lauderdale, Florida, United States, 33308
      • Holy Cross Hospital ( Site 0017)
    • Hollywood, Florida, United States, 33021
      • Memorial Regional Hospital-Memorial Cancer Institute ( Site 0104)
    • Orlando, Florida, United States, 32804
      • Advent Health ( Site 0013)
  • Indiana
    • Fort Wayne, Indiana, United States, 46804
      • Fort Wayne Medical Oncology and Hematology ( Site 0101)
  • Kentucky
    • Lexington, Kentucky, United States, 40503
      • Baptist Health Lexington ( Site 0099)
  • Missouri
    • Kansas City, Missouri, United States, 64111
      • St Luke's Hospital - Kansas City ( Site 0033)
  • Montana
    • Billings, Montana, United States, 59102
      • St. Vincent Frontier Cancer Center ( Site 0058)
  • New York
    • Bronx, New York, United States, 10461
      • Montefiore Medical Center [Bronx, NY] ( Site 0040)
  • Tennessee
    • Knoxville, Tennessee, United States, 37920
      • The University of Tennessee Medical Center ( Site 0050)
    • Nashville, Tennessee, United States, 37203
      • Tennessee Oncology ( Site 0051)
  • Texas
    • Houston, Texas, United States, 77030
      • Oncology Consultants, PA ( Site 0052)
    • Houston, Texas, United States, 77090
      • Millennium Physicians - Oncology ( Site 0097)
  • Virginia
    • Blacksburg, Virginia, United States, 24060
      • Oncology & Hematology Assoc. SW Virginia, Inc., DBA Blue Ridge Cancer Care ( Site 0100)
  • West Virginia
    • Morgantown, West Virginia, United States, 26506
      • West Virginia University ( Site 0056)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Has pathologically (histologically or cytologically) confirmed diagnosis of squamous or nonsquamous non-small cell lung cancer (NSCLC)
• Has Stage IV (T any, N any, M1a, M1b, or M1c - American Joint Committee on Cancer 8th Edition) squamous or nonsquamous NSCLC
• Has confirmation that epidermal growth factor receptor (EGFR), Anaplastic lymphoma kinase (ALK), or ROS Proto-Oncogene 1, Receptor Tyrosine Kinase (ROS1)-directed therapy is not indicated in nonsquamous NSCLC as well as mixed nonsquamous/squamous NSCLC. Participants with purely squamous NSCLC do not require testing
• Has not received prior systemic treatment for their metastatic NSCLC. Participants who received adjuvant or neoadjuvant therapy are eligible if the adjuvant/neoadjuvant therapy was completed at least 12 months prior to the development of metastatic disease
• Has an Eastern Cooperative Oncology Group (ECOG) performance score (PS) of 0 or 1
• Male participants are eligible to participate if they agree to use contraception as per protocol unless confirmed to be azoospermic
• A female participant is eligible to participate if she is not pregnant or breastfeeding, and at least one of the following conditions applies: is not a woman of childbearing potential (WOCBP) or is a WOCBP who agrees of using a contraceptive method per protocol
• Has measurable disease per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as assessed by the local site investigator/radiology
• Submit an archival tumor tissue sample or newly obtained core or incisional biopsy of a tumor lesion not previously irradiated for PD-L1 status determination prior to randomization
• Has adequate organ function

Exclusion Criteria:

• Has a known additional malignancy that is progressing or has required active treatment within the past 3 years
• Has known central nervous system (ie, brain and/or spinal cord) metastases and/or carcinomatous meningitis. Participants with treated brain metastases may participate only if they satisfy all of the following: a) Have no evidence of new or enlarging brain metastases confirmed by post-treatment repeat brain imaging performed at least 4 weeks after pretreatment brain imaging, and b) Are neurologically stable without the need for steroids for at least 14 days before first dose of trial treatment as per local site assessment
• Has severe hypersensitivity to study intervention and/or any of its excipients
• Has an active autoimmune disease that has required systemic treatment in past 2 years
• Has a history of (noninfectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease
• Has an active infection requiring systemic therapy
• Has a known history of human immunodeficiency virus (HIV) infection and/or Hepatitis B infection or known active Hepatitis C infection
• Has a known psychiatric or substance abuse disorder that would interfere with the participant's ability to cooperate with the requirements of the study
• Has symptomatic ascites or pleural effusion. A participant who is clinically stable after treatment for these conditions is eligible
• Before the first dose of study intervention: a) Has received prior systemic cytotoxic chemotherapy for metastatic NSCLC b) Has received antineoplastic biological therapy for metastatic NSCLC c) Has had major surgery (<3 weeks prior to first dose) d) Has received prior therapy with an anti-programmed cell death 1 (anti-PD-1), anti-programmed cell death ligand 1 (anti-PD-L1), or anti-programmed cell death ligand 2 (anti-PD-L2) agent or with an agent directed to another stimulatory or coinhibitory T-cell receptor
• Received radiation therapy to the lung that is >30 Gray within 6 months of the first dose of study intervention
• Is expected to require any other form of antineoplastic therapy while on study
• For participants with nonsquamous histology: Is unable to interrupt aspirin or other Non-steroidal anti-inflammatory drugs (NSAIDs), other than an aspirin dose ≤1.3 g/day, for a 5-day period
• For participants with nonsquamous histology: Is unable or unwilling to take folic acid or vitamin B12 supplementation
• Has received prior radiotherapy within 2 weeks of start of study intervention or have had a history of radiation pneumonitis. Participants must have recovered from all radiation-related toxicities and not require corticosteroids. A 1-week washout is permitted for palliative radiation (≤2 weeks of radiotherapy) to non-CNS disease
• Has received a live or live attenuated vaccine within 30 days prior to the first dose of study intervention
• Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks prior to the first dose of study intervention
• Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior the first dose of study intervention
• Has had an allogenic tissue/solid organ transplant

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm A: Pembrolizumab SC + Platinum Doublet Chemotherapy; Participants receive pembrolizumab subcutaneous (SC) administration on Day 1 of each cycle (cycle length = 3 weeks) for up to 35 cycles (up to ~2 years) PLUS paclitaxel IV (on Day 1 of each cycle) OR nab-paclitaxel IV (on Days 1, 8, and 15 of each cycle) and carboplatin IV (on Day 1 of each cycle) for 4 cycles for squamous non-small cell lung cancer (NSCLC); PLUS carboplatin IV (on Day 1 of each cycle) Or cisplatin IV (on Day 1 of each cycle) for 4 cycles and pemetrexed IV (on Day 1 of each cycle) until progression, intolerable adverse events, or participant/physician decision for non-squamous NSCLC.	Drug: Carboplatin; IV infusion; Other Names: Paraplatin; Paraplatin NovaPlus; Drug: Pemetrexed; IV infusion; Other Names: Alimta; LY231514; Pemetrexed Disodium; Drug: Cisplatin; IV infusion; Other Names: Platinol-AQ; Biological: Pembrolizumab SC; SC injection; Drug: Paclitaxel; IV injection; Other Names: Taxol; Nov-Onxol; Onxol; Paclitaxel Novaplus; Drug: Nab-Paclitaxel; IV infusion; Other Names: Abraxane; Nanoparticle albumin-bound paclitaxel
Active Comparator: Arm B: Pembrolizumab IV + Platinum Doublet Chemotherapy; Participants receive pembrolizumab intravenous (IV) administration on Day 1 of each cycle (cycle length = 3 weeks) for up to 35 cycles (up to ~2 years) PLUS paclitaxel IV (on Day 1 of each cycle) OR nab-paclitaxel IV (on Days 1, 8, and 15 of each cycle) and carboplatin IV (on Day 1 of each cycle) for 4 cycles for squamous non-small cell lung cancer (NSCLC); PLUS carboplatin IV (on Day 1 of each cycle) Or cisplatin IV (on Day 1 of each cycle) for 4 cycles and pemetrexed IV (on Day 1 of each cycle) until progression, intolerable adverse events, or participant/physician decision for non-squamous NSCLC.	Drug: Carboplatin; IV infusion; Other Names: Paraplatin; Paraplatin NovaPlus; Drug: Pemetrexed; IV infusion; Other Names: Alimta; LY231514; Pemetrexed Disodium; Drug: Cisplatin; IV infusion; Other Names: Platinol-AQ; Drug: Paclitaxel; IV injection; Other Names: Taxol; Nov-Onxol; Onxol; Paclitaxel Novaplus; Drug: Nab-Paclitaxel; IV infusion; Other Names: Abraxane; Nanoparticle albumin-bound paclitaxel; Biological: Pembrolizumab IV; IV injection; Other Names: MK-3475; SCH 900475; KEYTRUDA®

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cycle 1 Area Under The Curve From 0-3 Weeks (AUC 0-3wks) of Pembrolizumab	Cycle 1 AUC0-3wks is defined as the area under the concentration-time curve for pembrolizumab in plasma over a 3-week dosing interval in Cycle 1. Each cycle is 21 days.	Cycle 1: predose and postdose day 1; days 2, 3, 4, 5, 6, 7, 10, and 15. Cycle 2: predose day 1. Each cycle is 21 days.
Cycle 6 Model-Based Minimal Concentration (Ctrough) of Pembrolizumab	Cycle 6 model-based Ctrough is defined as the lowest concentration of pembrolizumab in plasma at the end of the dosing interval in Cycle 6, as predicted by the pharmacokinetic (PK) model based on historical intravenous pembrolizumab PK data. Each cycle is 21 days.	Cycle 6: predose day 1; days 2, 3, 4, 5, 6, 7, 10, and 15. Cycle 7: predose day 1. Each cycle is 21 days.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival (OS)	OS is defined as the time from randomization to death due to any cause.	Up to approximately 5 years
Number of Participants Who Experienced an Adverse Event (AE)	An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention. The number of participants who experience an AE will be reported.	Up to approximately 28 months
Number of Participants Who Discontinued Study Treatment Due to an AE	An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of study intervention. The number of participants who discontinue study treatment due to an AE will be presented.	Up to approximately 25 months
Anti-Drug Antibodies (ADAs) Incidence After Administration of Pembrolizumab	ADA incidence will be assessed by analyzing the development of ADAs following administration of pembrolizumab SC and pembrolizumab IV.	Up to approximately 26 months
Objective Response (OR) Per Response Evaluation Criteria In Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by Blinded Independent Central Review (BICR)	The OR rate is defined as the percentage of participants who achieve a confirmed complete response (CR: disappearance of all target lesions) or Partial Response (PR: at least a 30% decrease in the sum of diameters of target lesions) per RECIST 1.1 as assessed by BICR.	Up to approximately 5 years
Cycle 1 Observed Ctrough of Pembrolizumab	Cycle 1 observed Ctrough is defined as the lowest observed concentration of pembrolizumab in plasma at the end of the dosing interval in Cycle 1. Each cycle is 21 days.	Predose Cycle 2 day 1. Each cycle is 21 days.
Cycle 1 Maximum Concentration (Cmax) of Pembrolizumab	Cycle 1 Cmax is defined as the observed peak concentration of pembrolizumab in plasma over the dosing interval in Cycle 1. Each cycle is 21 days.	Cycle 1: predose day 1; days 2, 3, 4, 5, 6, 7, 10, and 15. Cycle 2: predose day 1. Each cycle is 21 days.
Cycle 6 AUC 0-3wks of Pembrolizumab	Cycle 6 AUC0-3wks is defined as the area under the concentration-time curve for pembrolizumab in plasma over a 3-week dosing interval in Cycle 6. Each cycle is 21 days.	Cycle 6: predose and postdose day 1; days 2, 3, 4, 5, 6, 7, 10, and 15. Cycle 7: predose day 1. Each cycle is 21 days.
Cycle 6 Cmax of Pembrolizumab	Cmax in Cycle 6 is defined as the observed peak concentration of pembrolizumab in plasma over the dosing interval in Cycle 6. Each cycle is 21 days.	Cycle 6: predose and postdose day 1; days 2, 3, 4, 5, 6, 7, 10, and 15. Cycle 7: predose day 1. Each cycle is 21 days.
Cycle 6 Observed Ctrough of Pembrolizumab	Cycle 6 observed Ctrough is defined as the lowest observed concentration of pembrolizumab in plasma at the end of the dosing interval in Cycle 6. Each cycle is 21 days.	Predose Cycle 7 day 1. Each cycle is 21 days.
Progression-Free Survival (PFS) Per RECIST 1.1 as Assessed by BICR	PFS is defined as the time from randomization to the first documented PD per RECIST 1.1 by BICR or death due to any cause, whichever occurs first. PD is defined as ≥20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of ≥5 mm. The appearance of one or more new lesions is also considered PD.	Up to approximately 5 years
Duration of Response (DOR) Per RECIST 1.1 as Assessed by BICR	For participants who show confirmed CR (disappearance of all target lesions) or PR (at least a 30% decrease in the sum of diameters of target lesions) per RECIST 1.1, duration of response is defined as the time from the first documented evidence of CR or PR until disease progression (PD) per RECIST 1.1 by BICR or death due to any cause, whichever occurs first. PD is defined as at least a 20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of one or more new lesions is also considered PD.	Up to approximately 5 years

Collaborators and Investigators

• Sponsor: Merck Sharp & Dohme LLC
• Investigators: Study Director: Medical Director, Merck Sharp & Dohme LLC

Publications and helpful links

Helpful Links

• Merck Clinical Trials Information
• Plain Language Summary

Study record dates

Study Major Dates

• Study Start (Actual): August 5, 2021
• Primary Completion (Actual): April 4, 2023
• Study Completion (Estimated): October 14, 2026

Study Registration Dates

• First Submitted: July 6, 2021
• First Submitted That Met QC Criteria: July 6, 2021
• First Posted (Actual): July 9, 2021

Study Record Updates

• Last Update Posted (Actual): December 3, 2024
• Last Update Submitted That Met QC Criteria: November 14, 2024
• Last Verified: November 1, 2024

More Information

Terms related to this study

• Keywords: Programmed Cell Death 1 (PD1, PD-1); Programmed Cell Death-Ligand 1 (PDL1, PD-L1); Programmed Cell Death-Ligand 2 (PDL2, PD-L2)
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Respiratory Tract Diseases; Lung Diseases; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Antineoplastic Agents, Immunological; Immune Checkpoint Inhibitors; Antineoplastic Agents; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Folic Acid Antagonists; Nucleic Acid Synthesis Inhibitors; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Phytogenic; Albumin-Bound Paclitaxel; Pemetrexed; Carboplatin; Pembrolizumab; Paclitaxel
• Other Study ID Numbers: 3475-A86; MK-3475-A86 (Other Identifier: MSD); jRCT2021210032 (Registry Identifier: jRCT (Japan Registry of Clinical Trials)); 2020-002729-27 (EudraCT Number); 2023-508308-40 (Registry Identifier: EU CT); U1111-1298-0215 (Other Identifier: UTN)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No