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)

NCT ID: NCT04956692

Last Updated: 2024-12-03

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE3
• Total Enrollment: 531 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-08-05
• Study Completion Date: 2026-10-14

Brief 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 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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

Pembrolizumab SC

Intervention Type: BIOLOGICAL

SC injection

Paclitaxel

Intervention Type: DRUG

IV injection

Nab-Paclitaxel

Intervention Type: DRUG

IV infusion

Carboplatin

Intervention Type: DRUG

IV infusion

Cisplatin

Intervention Type: DRUG

IV infusion

Pemetrexed

Intervention Type: DRUG

IV infusion

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.

Group Type: ACTIVE_COMPARATOR

Pembrolizumab IV

Intervention Type: BIOLOGICAL

IV injection

Paclitaxel

Intervention Type: DRUG

IV injection

Nab-Paclitaxel

Intervention Type: DRUG

IV infusion

Carboplatin

Intervention Type: DRUG

IV infusion

Cisplatin

Intervention Type: DRUG

IV infusion

Pemetrexed

Intervention Type: DRUG

IV infusion

Interventions

Pembrolizumab SC

SC injection

Intervention Type: BIOLOGICAL

Pembrolizumab IV

IV injection

Intervention Type: BIOLOGICAL

Paclitaxel

IV injection

Intervention Type: DRUG

Nab-Paclitaxel

IV infusion

Intervention Type: DRUG

Carboplatin

IV infusion

Intervention Type: DRUG

Cisplatin

IV infusion

Intervention Type: DRUG

Pemetrexed

IV infusion

Intervention Type: DRUG

Other Intervention Names

MK-3475; KEYTRUDA®; SCH 900475; Nov-Onxol; Onxol; Paclitaxel Novaplus; Taxol; Abraxane; Nanoparticle albumin-bound paclitaxel; Paraplatin; Paraplatin NovaPlus; Platinol-AQ; LY231514; Alimta; Pemetrexed Disodium

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Merck Sharp & Dohme LLC

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Medical Director

Role: STUDY_DIRECTOR

Merck Sharp & Dohme LLC

Locations

Fujita Health University Hospital ( Site 3007)

Toyoake, Aichi-ken, Japan

Ehime University Hospital ( Site 3005)

Tōon, Ehime, Japan

Kurume University Hospital ( Site 3006)

Kurume, Fukuoka, Japan

National Hospital Organization Hokkaido Cancer Center ( Site 3014)

Sapporo, Hokkaido, Japan

Kanazawa University Hospital ( Site 3004)

Kanazawa, Ishikawa-ken, Japan

Kanagawa Cardiovascular and Respiratory Center ( Site 3003)

Yokohama, Kanagawa, Japan

Miyagi Cancer Center ( Site 3000)

Natori-shi, Miyagi, Japan

Sendai Kousei Hospital ( Site 3015)

Sendai, Miyagi, Japan

Kurashiki Central Hospital ( Site 3013)

Kurashiki, Okayama-ken, Japan

Kansai Medical University Hospital ( Site 3016)

Hirakata, Osaka, Japan

National Hospital Organization Kinki-chuo Chest Medical Center ( Site 3009)

Sakai, Osaka, Japan

Osaka Medical and Pharmaceutical University Hospital ( Site 3017)

Takatsuki, Osaka, Japan

Chiba University Hospital ( Site 3008)

Chiba, , Japan

National Hospital Organization Kyushu Medical Center ( Site 3001)

Fukuoka, , Japan

St. Bernards Medical Center ( Site 0103)

Jonesboro, Arkansas, United States

St Joseph Heritage Healthcare-Oncology ( Site 0102)

Fullerton, California, United States

Cancer Blood and Specialty Clinic ( Site 0105)

Los Alamitos, California, United States

PIH Health Hematology Medical Oncology ( Site 0106)

Whittier, California, United States

Holy Cross Hospital ( Site 0017)

Fort Lauderdale, Florida, United States

Memorial Regional Hospital-Memorial Cancer Institute ( Site 0104)

Hollywood, Florida, United States

Advent Health ( Site 0013)

Orlando, Florida, United States

Fort Wayne Medical Oncology and Hematology ( Site 0101)

Fort Wayne, Indiana, United States

Baptist Health Lexington ( Site 0099)

Lexington, Kentucky, United States

St Luke's Hospital - Kansas City ( Site 0033)

Kansas City, Missouri, United States

St. Vincent Frontier Cancer Center ( Site 0058)

Billings, Montana, United States

Montefiore Medical Center [Bronx, NY] ( Site 0040)

The Bronx, New York, United States

National Hospital Organization Kyushu Cancer Center ( Site 3002)

Fukuoka, , Japan

Okayama University Hospital ( Site 3012)

Okayama, , Japan

Osaka International Cancer Institute ( Site 3018)

Osaka, , Japan

The University of Tennessee Medical Center ( Site 0050)

Knoxville, Tennessee, United States

Tennessee Oncology ( Site 0051)

Nashville, Tennessee, United States

Oncology Consultants, PA ( Site 0052)

Houston, Texas, United States

Millennium Physicians - Oncology ( Site 0097)

Houston, Texas, United States

Tokushima University Hospital ( Site 3019)

Tokushima, , Japan

Juntendo University Hospital ( Site 3011)

Tokyo, , Japan

Showa University Hospital ( Site 3010)

Tokyo, , Japan

Hospital Nacional Carlos Alberto Seguin Escobedo ESSALUD ( Site 0704)

Arequipa, Ariqipa, Peru

Clínica Peruano-Americana de Trujillo ( Site 0701)

Trujillo, La Libertad, Peru

Oncosalud ( Site 0706)

Lima, Muni Metro de Lima, Peru

Clinica Internacional Sede San Borja ( Site 0705)

Lima, , Peru

Instituto Nacional de Enfermedades Neoplasicas ( Site 0703)

Lima, , Peru

Hospital Nacional Cayetano Heredia ( Site 0700)

Lima, , Peru

Przychodnia Lekarska KOMED ( Site 1202)

Konin, Greater Poland Voivodeship, Poland

Oncology & Hematology Assoc. SW Virginia, Inc., DBA Blue Ridge Cancer Care ( Site 0100)

Blacksburg, Virginia, United States

West Virginia University ( Site 0056)

Morgantown, West Virginia, United States

HOSPITAL EVANGÉLICO DE CACHOEIRO DE ITAPEMIRIM ( Site 0307)

Cachoeiro de Itapemirim, Espírito Santo, Brazil

Hospital Sao Vicente de Paulo ( Site 0311)

Passo Fundo, Rio Grande do Sul, Brazil

Instituto Joinvilense de Hematologia e Oncologia ( Site 0308)

Joinville, Santa Catarina, Brazil

Fundacao Faculdade Regional de Medicina de Sao Jose do Rio Preto ( Site 0305)

São José do Rio Preto, São Paulo, Brazil

Núcleo de Pesquisa Clínica da Rede São Camilo ( Site 0304)

São Paulo, São Paulo, Brazil

Nouvel Hôpital Civil (NHC) ( Site 1018)

Strasbourg, Bas-Rhin, France

CHU Limoges CHU Dupuytren ( Site 1011)

Limoges, Haute-Vienne, France

Hôpital Foch ( Site 1019)

Suresnes, Hauts-de-Seine, France

Institut Regional du Cancer de Montpellier - ICM ( Site 1003)

Montpellier, Herault, France

Centre Hospitalier Sud Réunion ( Site 1020)

Saint-Pierre, La Reunion, France

Hopital Guillaume & Rene Laennec ( Site 1007)

Saint-Herblain, Loire-Atlantique, France

Centre Hospitalier de Pau ( Site 1016)

Pau, Pyrenees-Atlantiques, France

CHU de Rouen ( Site 1013)

Rouen, Seine-Maritime, France

Hopital Cochin ( Site 1002)

Paris, , France

Centro de Investigaciones Clinicas de Latinoamerica S.A. - CELAN ( Site 0602)

Guatemala City, , Guatemala

Clinica Privada Dr. Rixci Ramirez ( Site 0601)

Guatemala City, , Guatemala

INTERVASC ( Site 0605)

Guatemala City, , Guatemala

Grupo Angeles SA ( Site 0604)

Guatemala City, , Guatemala

Centro Regional de Sub Especialidades Médicas SA ( Site 0600)

Quetzaltenango, , Guatemala

Bacs-Kiskun Megyei Korhaz-Onkoradiologiai Kozpont ( Site 1106)

Kecskemét, Bács-Kiskun county, Hungary

Petz Aladar Megyei Oktato Korhaz ( Site 1110)

Győr, Győr-Moson-Sopron, Hungary

Jasz Nagykun Szolnok Megyei Hetenyi Geza Korhaz Rendelointezet ( Site 1103)

Szolnok, Jász-Nagykun-Szolnok, Hungary

Tudogyogyintezet Torokbalint ( Site 1105)

Törökbálint, Pest County, Hungary

Veszprem Megyei Tudogyogyintezet ( Site 1108)

Farkasgyepű, Veszprém megye, Hungary

Zala Megyei Szent Rafael Korhaz ( Site 1111)

Zalagerszeg, Zalaegerszeg, Hungary

Semmelweis University-Pulmonológiai Klinika ( Site 1114)

Budapest, , Hungary

Orszagos Koranyi Pulmonologiai Intezet ( Site 1104)

Budapest, , Hungary

Centrum Onkologii im prof Franciszka Lukaszczyka ( Site 1201)

Bydgoszcz, Kuyavian-Pomeranian Voivodeship, Poland

Mazowiecki Szpital Wojewódzki w Siedlcach-Siedleckie Centrum Onkologii ( Site 1206)

Siedlce, Masovian Voivodeship, Poland

Narodowy Instytut Onkologii im. Marii Sklodowskiej-Curie - Panstwowy Instytut Badawczy w Warszawie (

Warsaw, Masovian Voivodeship, Poland

Centrum Pulmonologii i Torakochirurgii w Bystrej ( Site 1205)

Bystra, Silesian Voivodeship, Poland

Szpital Wojewodzki im. Mikolaja Kopernika ( Site 1200)

Koszalin, West Pomeranian Voivodeship, Poland

Cardiomed SRL Cluj-Napoca ( Site 1313)

Cluj-Napoca, Cluj, Romania

Institutul Oncologic Prof.Dr. Ion Chiricuta Cluj-Napoca ( Site 1303)

Cluj-Napoca, Cluj, Romania

SC Radiotherapy Center Cluj SRL ( Site 1307)

Comuna Floresti, Cluj, Romania

S.C. Centrul de Oncologie Sf. Nectarie SRL ( Site 1304)

Craiova, Dolj, Romania

Centrul de Oncologie Oncolab-Medical Oncology ( Site 1312)

Craiova, Dolj, Romania

Spitalul Municipal Ploiesti ( Site 1308)

Ploieşti, Prahova, Romania

Policlinica Oncomed SRL ( Site 1302)

Timișoara, Timiș County, Romania

S.C.Focus Lab Plus S.R.L ( Site 1301)

Bucharest, , Romania

Spitalul Universitar de Urgenta Bucuresti ( Site 1305)

Bucharest, , Romania

SPBU Clinic of Advanced medical technologies n.a. N. I. Pirogov ( Site 1406)

Saint Petersburg, Sankt-Peterburg, Russia

National Medical Research Center of Oncology N.A. N.N. Petrov ( Site 1407)

Saint Petersburg, Sankt-Peterburg, Russia

Saint-Petersburg Scientific-Practical Center of Specialized Kinds of Medical Care (o) ( Site 1424)

Saint Petersburg, Sankt-Peterburg, Russia

Republican Clinical Oncology Dispensary-Chemotherapy #1 ( Site 1425)

Kazan', Tatarstan, Respublika, Russia

SPb SBHI City Clinical Oncological Dispensary ( Site 1409)

Saint Petersburg, , Russia

Wits Clinical Research ( Site 1510)

Johannesburg, Gauteng, South Africa

Steve Biko Academic Hospital ( Site 1506)

Pretoria, Gauteng, South Africa

Marry Potter Oncology Centre ( Site 1502)

Pretoria, Gauteng, South Africa

Sandton Oncology Medical Group PTY LTD ( Site 1505)

Sandton, Gauteng, South Africa

Chris Hani Baragwanath Academic Hospital-Wits Clinical Research Bara ( Site 1513)

Soweto, Gauteng, South Africa

The Oncology Centre ( Site 1507)

Durban, Limpopo, South Africa

Cape Town Oncology Trials Pty Ltd ( Site 1500)

Kraaifontein, Western Cape, South Africa

Chungnam National University Hospital ( Site 2002)

Daejeon, Chungcheongnam-do, South Korea

Chonnam National University Hwasun Hospital-Pulmonology ( Site 2000)

Hwasun, Jeonranamdo, South Korea

Korea University Guro Hospital ( Site 2003)

Seoul, , South Korea

Hospital Insular de Gran Canaria-Oncology ( Site 1604)

Las Palmas de Gran Canaria, Las Palmas, Spain

H.U. Vall de Hebron ( Site 1600)

Barcelona, , Spain

Hospital Juan Ramon Jimenez ( Site 1602)

Huelva, , Spain

Hospital Universitario Lucus Augusti ( Site 1603)

Lugo, , Spain

Hospital Universitario La Paz ( Site 1601)

Madrid, , Spain

Changhua Christian Hospital ( Site 2104)

Changhua, , Taiwan

National Taiwan University Hospital Hsin-Chu Branch ( Site 2103)

Hsinchu, , Taiwan

Kaohsiung Medical University Chung-Ho Memorial Hospital ( Site 2107)

Kaohsiung City, , Taiwan

National Cheng Kung University Hospital ( Site 2105)

Tainan City, , Taiwan

National Taiwan University Hospital ( Site 2101)

Taipei, , Taiwan

Taipei Veterans General Hospital ( Site 2106)

Taipei, , Taiwan

Chang Gung Medical Foundation-Linkou Branch ( Site 2102)

Taoyuan District, , Taiwan

Gulhane Egitim ve Arastirma Hastanesi ( Site 1704)

Ankara, , Turkey (Türkiye)

Ankara Sehir Hastanesi ( Site 1702)

Ankara, , Turkey (Türkiye)

TC Saglik Bakanligi Goztepe Prof. Dr. Suleyman Yalcin Sehir Hastanesi-oncology ( Site 1701)

Istanbul, , Turkey (Türkiye)

Ege Universitesi Tip Fakultesi Hastanesi ( Site 1703)

Izmir, , Turkey (Türkiye)

Inonu Universitesi Turgut Ozal Tip Merkezi ( Site 1707)

Malatya, , Turkey (Türkiye)

Medical Center Mriya Med-Service ( Site 1805)

Kryvyi Rih, Dnipropetrovsk Oblast, Ukraine

Communal non profit enterprise Regional Clinical Oncology Center ( Site 1806)

Kharkiv, Kharkivs’ka Oblast’, Ukraine

Ukrainian Center of Tomotherapy ( Site 1807)

Kropyvnytskyi, Kirovohrad Oblast, Ukraine

Medical Center Asklepion LLC ( Site 1804)

Khodosovka, Kyivska Oblast, Ukraine

Municipal non-profit enterprise'Odesa Regional Clinical Hosp-Thoracic surgery department. ( Site 181

Odesa, Odesa Oblast, Ukraine

Kremenchuk Regional Oncology Center ( Site 1811)

Kremenchuk, Poltava Oblast, Ukraine

Kyiv City Clinical Oncology Centre ( Site 1809)

Kyiv, , Ukraine

Medical Center Dobrobut Clinic ( Site 1808)

Kyiv, , Ukraine

Countries

United States; Brazil; France; Guatemala; Hungary; Japan; Peru; Poland; Romania; Russia; South Africa; South Korea; Spain; Taiwan; Turkey (Türkiye); Ukraine

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Related Links

https://www.merckclinicaltrials.com/

Merck Clinical Trials Information

https://msd.trialsummaries.com/Study/StudyDetails?id=26224&tenant=MT_MSD_9011

Plain Language Summary

Other Identifiers

MK-3475-A86

Identifier Type: OTHER

Identifier Source: secondary_id

jRCT2021210032

Identifier Type: REGISTRY

Identifier Source: secondary_id

2023-508308-40

Identifier Type: REGISTRY

Identifier Source: secondary_id

U1111-1298-0215

Identifier Type: OTHER

Identifier Source: secondary_id

2020-002729-27

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

3475-A86

Identifier Type: -

Identifier Source: org_study_id