Non-Small Cell Lung CancerPhase 3NCT04956692
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 Phase 3 study testing Pembrolizumab SC, Pembrolizumab IV and Paclitaxel in people with Non-Small Cell Lung Cancer, run by Merck Sharp & Dohme LLC at 126 sites in 16 countries.
Trial summary
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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Non-Small Cell Lung Cancer
- What is being tested?
- Pembrolizumab SC, Pembrolizumab IV and Paclitaxel
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 531 participants
- Where
- 126 sitesin 16 countries
- Study dates
- 5 Aug 2021to 24 Aug 2026
- Phase
- Phase 3
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Show all 10Show fewer
- 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
Who cannot join
- 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
Show all 19Show fewer
- 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
Trial locations and contacts
126 sites in 16 countries.
126 sites in 16 countries
Japan20 sites
Chiba University Hospital ( Site 3008)
Chiba, 260-8677
National Hospital Organization Kyushu Medical Center ( Site 3001)
Fukuoka, 810-8563
National Hospital Organization Kyushu Cancer Center ( Site 3002)
Fukuoka, 811-1395
Kansai Medical University Hospital ( Site 3016)
Hirakata, Osaka, 573-1191
Kanazawa University Hospital ( Site 3004)
Kanazawa, Ishikawa-ken, 920-8641
Kurashiki Central Hospital ( Site 3013)
Kurashiki, Okayama-ken, 710-8602
Kurume University Hospital ( Site 3006)
Kurume, Fukuoka, 830-0011
Miyagi Cancer Center ( Site 3000)
Natori-shi, Miyagi, 981-1293
Okayama University Hospital ( Site 3012)
Okayama, 7008558
Osaka International Cancer Institute ( Site 3018)
Osaka, 541-8567
National Hospital Organization Kinki-chuo Chest Medical Center ( Site 3009)
Sakai, Osaka
National Hospital Organization Hokkaido Cancer Center ( Site 3014)
Sapporo, Hokkaido, 003-0804
Sendai Kousei Hospital ( Site 3015)
Sendai, Miyagi, 980-0873
Osaka Medical and Pharmaceutical University Hospital ( Site 3017)
Takatsuki, Osaka, 569-8686
Tokushima University Hospital ( Site 3019)
Tokushima, 770-8503
Juntendo University Hospital ( Site 3011)
Tokyo, 113-8431
Showa University Hospital ( Site 3010)
Tokyo, 142-8666
Ehime University Hospital ( Site 3005)
Tōon, Ehime, 791-0295
Fujita Health University Hospital ( Site 3007)
Toyoake, Aichi-ken, 4701192
Kanagawa Cardiovascular and Respiratory Center ( Site 3003)
Yokohama, Kanagawa, 236-0051
United States18 sites
St. Vincent Frontier Cancer Center ( Site 0058)
Billings, Montana, 59102
Oncology & Hematology Assoc. SW Virginia, Inc., DBA Blue Ridge Cancer Care ( Site 0100)
Blacksburg, Virginia, 24060
Holy Cross Hospital ( Site 0017)
Fort Lauderdale, Florida, 33308
Fort Wayne Medical Oncology and Hematology ( Site 0101)
Fort Wayne, Indiana, 46804
St Joseph Heritage Healthcare-Oncology ( Site 0102)
Fullerton, California, 92835
Memorial Regional Hospital-Memorial Cancer Institute ( Site 0104)
Hollywood, Florida, 33021
Oncology Consultants, PA ( Site 0052)
Houston, Texas, 77030
Millennium Physicians - Oncology ( Site 0097)
Houston, Texas, 77090
St. Bernards Medical Center ( Site 0103)
Jonesboro, Arkansas, 72401
St Luke's Hospital - Kansas City ( Site 0033)
Kansas City, Missouri, 64111
The University of Tennessee Medical Center ( Site 0050)
Knoxville, Tennessee, 37920
Baptist Health Lexington ( Site 0099)
Lexington, Kentucky, 40503
Cancer Blood and Specialty Clinic ( Site 0105)
Los Alamitos, California, 90720
West Virginia University ( Site 0056)
Morgantown, West Virginia, 26506
Tennessee Oncology ( Site 0051)
Nashville, Tennessee, 37203
Advent Health ( Site 0013)
Orlando, Florida, 32804
Montefiore Medical Center [Bronx, NY] ( Site 0040)
The Bronx, New York, 10461
PIH Health Hematology Medical Oncology ( Site 0106)
Whittier, California, 90602
France9 sites
CHU Limoges CHU Dupuytren ( Site 1011)
Limoges, Haute-Vienne, 87042
Institut Regional du Cancer de Montpellier - ICM ( Site 1003)
Montpellier, Herault, 34298
Hopital Cochin ( Site 1002)
Paris, 75014
Centre Hospitalier de Pau ( Site 1016)
Pau, Pyrenees-Atlantiques, 64000
CHU de Rouen ( Site 1013)
Rouen, Seine-Maritime, 76031
Hopital Guillaume & Rene Laennec ( Site 1007)
Saint-Herblain, Loire-Atlantique, 44800
Centre Hospitalier Sud Réunion ( Site 1020)
Saint-Pierre, La Reunion, 97448
Nouvel Hôpital Civil (NHC) ( Site 1018)
Strasbourg, Bas-Rhin, 67091
Hôpital Foch ( Site 1019)
Suresnes, Hauts-de-Seine, 92150
Romania9 sites
S.C.Focus Lab Plus S.R.L ( Site 1301)
Bucharest, 022548
Spitalul Universitar de Urgenta Bucuresti ( Site 1305)
Bucharest, 050098
Cardiomed SRL Cluj-Napoca ( Site 1313)
Cluj-Napoca, Cluj, 400015
Institutul Oncologic Prof.Dr. Ion Chiricuta Cluj-Napoca ( Site 1303)
Cluj-Napoca, Cluj, 400015
SC Radiotherapy Center Cluj SRL ( Site 1307)
Comuna Floresti, Cluj, 407280
S.C. Centrul de Oncologie Sf. Nectarie SRL ( Site 1304)
Craiova, Dolj, 200347
Centrul de Oncologie Oncolab-Medical Oncology ( Site 1312)
Craiova, Dolj, 200385
Spitalul Municipal Ploiesti ( Site 1308)
Ploieşti, Prahova, 100337
Policlinica Oncomed SRL ( Site 1302)
Timișoara, Timiș County, 300239
Hungary8 sites
Semmelweis University-Pulmonológiai Klinika ( Site 1114)
Budapest, 1083
Orszagos Koranyi Pulmonologiai Intezet ( Site 1104)
Budapest, 1121
Veszprem Megyei Tudogyogyintezet ( Site 1108)
Farkasgyepű, Veszprém megye, 8582
Petz Aladar Megyei Oktato Korhaz ( Site 1110)
Győr, Győr-Moson-Sopron, 9023
Bacs-Kiskun Megyei Korhaz-Onkoradiologiai Kozpont ( Site 1106)
Kecskemét, Bács-Kiskun county, 6000
Jasz Nagykun Szolnok Megyei Hetenyi Geza Korhaz Rendelointezet ( Site 1103)
Szolnok, Jász-Nagykun-Szolnok, 5000
Tudogyogyintezet Torokbalint ( Site 1105)
Törökbálint, Pest County, 2045
Zala Megyei Szent Rafael Korhaz ( Site 1111)
Zalagerszeg, Zalaegerszeg, 8900
Ukraine8 sites
Communal non profit enterprise Regional Clinical Oncology Center ( Site 1806)
Kharkiv, Kharkiv Oblast, 61070
Medical Center Asklepion LLC ( Site 1804)
Khodosovka, Kyivska Oblast, 08173
Kremenchuk Regional Oncology Center ( Site 1811)
Kremenchuk, Poltava Oblast, 39617
Ukrainian Center of Tomotherapy ( Site 1807)
Kropyvnytskyi, Kirovohrad Oblast, 25011
Medical Center Mriya Med-Service ( Site 1805)
Kryvyi Rih, Dnipropetrovsk Oblast, 50000
Kyiv City Clinical Oncology Centre ( Site 1809)
Kyiv, 03115
Medical Center Dobrobut Clinic ( Site 1808)
Kyiv, 03151
Municipal non-profit enterprise'Odesa Regional Clinical Hosp-Thoracic surgery department. ( Site 181
Odesa, Odesa Oblast, 65025
South Africa7 sites
The Oncology Centre ( Site 1507)
Durban, Limpopo, 4001
Wits Clinical Research ( Site 1510)
Johannesburg, Gauteng, 2193
Cape Town Oncology Trials Pty Ltd ( Site 1500)
Kraaifontein, Western Cape, 7570
Steve Biko Academic Hospital ( Site 1506)
Pretoria, Gauteng, 0002
Marry Potter Oncology Centre ( Site 1502)
Pretoria, Gauteng, 0181
Sandton Oncology Medical Group PTY LTD ( Site 1505)
Sandton, Gauteng, 2196
Chris Hani Baragwanath Academic Hospital-Wits Clinical Research Bara ( Site 1513)
Soweto, Gauteng, 2013
Taiwan7 sites
Changhua Christian Hospital ( Site 2104)
Changhua, 50006
National Taiwan University Hospital Hsin-Chu Branch ( Site 2103)
Hsinchu, 300
Kaohsiung Medical University Chung-Ho Memorial Hospital ( Site 2107)
Kaohsiung City, 807
National Cheng Kung University Hospital ( Site 2105)
Tainan, 704
National Taiwan University Hospital ( Site 2101)
Taipei, 10048
Taipei Veterans General Hospital ( Site 2106)
Taipei, 11217
Chang Gung Medical Foundation-Linkou Branch ( Site 2102)
Taoyuan, 333
Peru6 sites
Hospital Nacional Carlos Alberto Seguin Escobedo ESSALUD ( Site 0704)
Arequipa, Ariqipa, 04001
Oncosalud ( Site 0706)
Lima, Muni Metro de Lima, 15036
Clinica Internacional Sede San Borja ( Site 0705)
Lima, 15036
Instituto Nacional de Enfermedades Neoplasicas ( Site 0703)
Lima, 15038
Hospital Nacional Cayetano Heredia ( Site 0700)
Lima, 15102
Clínica Peruano-Americana de Trujillo ( Site 0701)
Trujillo, La Libertad, 13007
Poland6 sites
Centrum Onkologii im prof Franciszka Lukaszczyka ( Site 1201)
Bydgoszcz, Kuyavian-Pomeranian Voivodeship, 85-796
Centrum Pulmonologii i Torakochirurgii w Bystrej ( Site 1205)
Bystra, Silesian Voivodeship, 43-360
Przychodnia Lekarska KOMED ( Site 1202)
Konin, Greater Poland Voivodeship, 62-500
Szpital Wojewodzki im. Mikolaja Kopernika ( Site 1200)
Koszalin, West Pomeranian Voivodeship, 75-581
Mazowiecki Szpital Wojewódzki w Siedlcach-Siedleckie Centrum Onkologii ( Site 1206)
Siedlce, Masovian Voivodeship, 08-110
Narodowy Instytut Onkologii im. Marii Sklodowskiej-Curie - Panstwowy Instytut Badawczy w Warszawie (
Warsaw, Masovian Voivodeship, 02-781
Brazil5 sites
HOSPITAL EVANGÉLICO DE CACHOEIRO DE ITAPEMIRIM ( Site 0307)
Cachoeiro de Itapemirim, Espírito Santo, 29308-065
Instituto Joinvilense de Hematologia e Oncologia ( Site 0308)
Joinville, Santa Catarina, 89201260
Hospital Sao Vicente de Paulo ( Site 0311)
Passo Fundo, Rio Grande do Sul, 99010-080
Fundacao Faculdade Regional de Medicina de Sao Jose do Rio Preto ( Site 0305)
São José do Rio Preto, São Paulo, 15090-000
Núcleo de Pesquisa Clínica da Rede São Camilo ( Site 0304)
São Paulo, São Paulo, 04014-002
Guatemala5 sites
Centro de Investigaciones Clinicas de Latinoamerica S.A. - CELAN ( Site 0602)
Guatemala City, 01010
Clinica Privada Dr. Rixci Ramirez ( Site 0601)
Guatemala City, 01010
INTERVASC ( Site 0605)
Guatemala City, 01010
Grupo Angeles SA ( Site 0604)
Guatemala City, 01015
Centro Regional de Sub Especialidades Médicas SA ( Site 0600)
Quetzaltenango, 09001
Russia5 sites
Republican Clinical Oncology Dispensary-Chemotherapy #1 ( Site 1425)
Kazan', Tatarstan, Respublika, 420029
SPBU Clinic of Advanced medical technologies n.a. N. I. Pirogov ( Site 1406)
Saint Petersburg, Sankt-Peterburg, 190103
National Medical Research Center of Oncology N.A. N.N. Petrov ( Site 1407)
Saint Petersburg, Sankt-Peterburg, 197758
Saint-Petersburg Scientific-Practical Center of Specialized Kinds of Medical Care (o) ( Site 1424)
Saint Petersburg, Sankt-Peterburg, 197758
SPb SBHI City Clinical Oncological Dispensary ( Site 1409)
Saint Petersburg, 198255
Spain5 sites
H.U. Vall de Hebron ( Site 1600)
Barcelona, 08035
Hospital Juan Ramon Jimenez ( Site 1602)
Huelva, 21005
Hospital Insular de Gran Canaria-Oncology ( Site 1604)
Las Palmas de Gran Canaria, Las Palmas, 35001
Hospital Universitario Lucus Augusti ( Site 1603)
Lugo, 27003
Hospital Universitario La Paz ( Site 1601)
Madrid, 28046
Turkey (Türkiye)5 sites
Gulhane Egitim ve Arastirma Hastanesi ( Site 1704)
Ankara, 06010
Ankara Sehir Hastanesi ( Site 1702)
Ankara, 06800
TC Saglik Bakanligi Goztepe Prof. Dr. Suleyman Yalcin Sehir Hastanesi-oncology ( Site 1701)
Istanbul, 34722
Ege Universitesi Tip Fakultesi Hastanesi ( Site 1703)
Izmir, 35040
Inonu Universitesi Turgut Ozal Tip Merkezi ( Site 1707)
Malatya, 44280
South Korea3 sites
Chungnam National University Hospital ( Site 2002)
Daejeon, Chungcheongnam-do, 35015
Chonnam National University Hwasun Hospital-Pulmonology ( Site 2000)
Hwasun, Jeonranamdo, 58128
Korea University Guro Hospital ( Site 2003)
Seoul, 08308
About this study
Official title: 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.
- Conditions
- Non-Small Cell Lung Cancer
- Being tested
- Pembrolizumab SC, Pembrolizumab IV, Paclitaxel, Nab-Paclitaxel, Carboplatin
- Keywords
- Programmed Cell Death 1 (PD1, PD-1), Programmed Cell Death-Ligand 1 (PDL1, PD-L1), Programmed Cell Death-Ligand 2 (PDL2, PD-L2)
- Medical subject headings
- Carcinoma, Non-Small-Cell Lung, Parkinson Disease 4, Autosomal Dominant Lewy Body
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Pembrolizumab SCBiological
SC injection
Pembrolizumab IVBiological
Also called MK-3475, KEYTRUDA®, SCH 900475
IV injection
PaclitaxelDrug
Also called Nov-Onxol, Onxol, Paclitaxel Novaplus, Taxol
IV injection
Nab-PaclitaxelDrug
Also called Abraxane, Nanoparticle albumin-bound paclitaxel
IV infusion
CarboplatinDrug
Also called Paraplatin, Paraplatin NovaPlus
IV infusion
CisplatinDrug
Also called Platinol-AQ
IV infusion
PemetrexedDrug
Also called LY231514, Alimta, Pemetrexed Disodium
IV infusion
| Study group | Role | What they receive |
|---|---|---|
| Arm A: Pembrolizumab SC + Platinum Doublet Chemotherapy | Experimental | 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. Receives: Biological: Pembrolizumab SC; Drug: Paclitaxel; Drug: Nab-Paclitaxel; Drug: Carboplatin; Drug: Cisplatin; Drug: Pemetrexed |
| Arm B: Pembrolizumab IV + Platinum Doublet Chemotherapy | Active comparator | 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. Receives: Biological: Pembrolizumab IV; Drug: Paclitaxel; Drug: Nab-Paclitaxel; Drug: Carboplatin; Drug: Cisplatin; Drug: Pemetrexed |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: 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 outcomes (12)
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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: Predose Cycle 7 day 1. Each cycle is 21 days.
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.
Measured: 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.
Measured: Up to approximately 25 months
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.
Measured: Up to approximately 5 years
Overall Survival (OS)
OS is defined as the time from randomization to death due to any cause.
Measured: 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.
Measured: Up to approximately 5 years
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.
Measured: Up to approximately 26 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Jul 2021
- Study start5 Aug 2021
- Primary completion4 Apr 2023
- Study completion24 Aug 2026
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Non-Small Cell Lung CancerStudies of the same condition, open and under way.
- More trials run by Merck Sharp & Dohme LLCThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 531 participants (actual)
Sponsor and investigators
- Lead sponsor
- Merck Sharp & Dohme LLC
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Medical Director, Study director, Merck Sharp & Dohme LLC
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04956692
- Sponsor's protocol ID
- 3475-A86
- Other IDs
- MK-3475-A86, jRCT2021210032, 2023-508308-40-00, U1111-1298-0215, 2020-002729-27, 2023
- Status last verified
- Sep 2026
- First submitted
- 6 Jul 2021
- Last updated
- 7 Oct 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: https://trialstransparency.msdclinicaltrials.com/pdf/ProcedureAccessClinicalTrialData.pdf