A Study of Subcutaneous (SC) Pembrolizumab Coformulated With Berahyaluronidase Alfa (MK-3475A) vs Intravenous Pembrolizumab in Adult Participants With Metastatic Non-small Cell Lung Cancer (NSCLC) (MK-3475A-D77)

A Phase 3 Randomized, Open-label Clinical Study to Evaluate the Pharmacokinetics and Safety of Subcutaneous Pembrolizumab Coformulated With Hyaluronidase (MK-3475A) Versus Intravenous Pembrolizumab, Administered With Chemotherapy, in the First-line Treatment of Participants With Metastatic Non-small Cell Lung Cancer

This study is to assess the pharmacokinetics (PK) and safety of SC pembrolizumab formulated with berahyaluronidase alfa (MK-3475A) versus (vs) intravenous (IV) pembrolizumab (MK-3475), administered with chemotherapy in first line treatment of adult participants with metastatic non-small cell lung cancer. The primary hypotheses of this study are pembrolizumab formulated with berahyaluronidase alfa subcutaneous (SC) is noninferior to pembrolizumab IV with respect to PK parameters.

Study Overview

• Status: Active, not recruiting
• Conditions: Metastatic Non-small Cell Lung Cancer
• Intervention / Treatment: Drug: Pemetrexed; Drug: Cisplatin; Drug: Carboplatin; Drug: Paclitaxel; Drug: Nab-paclitaxel; Biological: Pembrolizumab; Drug: Filgrastim; Drug: Pegylated filgrastim; Biological: Pembrolizumab Formulated with Berahyaluronidase Alfa

• Study Type: Interventional
• Enrollment (Actual): 377
• Phase: Phase 3

Contacts and Locations

Study Locations

• Argentina
  • Córdoba, Argentina, X5004BAL
    • Hospital Italiano de Córdoba ( Site 1000)
  • Buenos Aires
    • Ciudad Autonoma de Buenos Aires, Buenos Aires, Argentina, C1199ABB
      • Hospital Italiano de Buenos Aires-Clinical Oncology ( Site 1005)
    • Mar del Plata, Buenos Aires, Argentina, B7600FZO
      • Instituto de Investigaciones Clínicas Mar del Plata ( Site 1001)
  • Buenos Aires F.D.
    • Buenos Aires, Buenos Aires F.D., Argentina, C1122AAL
      • Instituto Argentino de Diagnóstico y Tratamiento (IADT) ( Site 1002)
    • Buenos Aires, Buenos Aires F.D., Argentina, C1426ANZ
      • Instituto Alexander Fleming ( Site 1008)
    • Buenos Aires, Buenos Aires F.D., Argentina, C1430EGF
      • Clinica Adventista Belgrano-Oncology ( Site 1004)
  • Santa Fe Province
    • Rosario, Santa Fe Province, Argentina, S2000DVC
      • Sanatorio Parque ( Site 1003)
• Brazil
  • São Paulo, Brazil, 01509-010
    • A. C. Camargo Cancer Center ( Site 1106)
  • Ceará
    • Fortaleza, Ceará, Brazil, 60336-232
      • CRIO - CENTRO REGIONAL INTEGRADO DE ONCOLOGIA-Pesquisa Clínica ( Site 1102)
  • Pernambuco
    • Recife, Pernambuco, Brazil, 50040-000
      • Hospital de Cancer de Pernambuco ( Site 1107)
  • Rio Grande do Sul
    • Porto Alegre, Rio Grande do Sul, Brazil, 91350-200
      • Hospital Nossa Senhora da Conceição-Centro Integrado de Pesquisa em Oncologia ( Site 1100)
  • Santa Catarina
    • Joinville, Santa Catarina, Brazil, 89201-260
      • Instituto Joinvilense de Hematologia e Oncologia ( Site 1101)
• Chile
  • Coquimbo Region
    • La Serena, Coquimbo Region, Chile, 1720430
      • IC La Serena Research ( Site 1207)
  • Los Ríos Region
    • Valdivia, Los Ríos Region, Chile, 5112129
      • Oncocentro Valdivia ( Site 1201)
  • Region M. de Santiago
    • Santiago, Region M. de Santiago, Chile, 7500921
      • FALP-UIDO ( Site 1203)
    • Santiago, Region M. de Santiago, Chile, 7500994
      • Oncovida ( Site 1209)
    • Santiago, Region M. de Santiago, Chile, 8330024
      • Pontificia Universidad Catolica de Chile-Hemato-Oncology ( Site 1210)
    • Santiago, Region M. de Santiago, Chile, 8380455
      • Instituto Nacional del Cancer-CR Investigación ( Site 1211)
    • Santiago, Region M. de Santiago, Chile, 8420383
      • Bradfordhill-Clinical Area ( Site 1202)
• China
  • Anhui
    • Hefei, Anhui, China, 230071
      • Anhui Provincial Hospital-Cancer Chemotherapy Department ( Site 4503)
  • Beijing Municipality
    • Beijing, Beijing Municipality, China, 100142
      • Beijing Cancer hospital-intrathoratic deparmtment II ( Site 4510)
    • Beijing, Beijing Municipality, China, 100730
      • Beijing Peking Union Medical College Hospital-pneumology department ( Site 4501)
    • Beijing, Beijing Municipality, China, 101149
      • Beijing Chest Hospital,Capital Medical University ( Site 4511)
  • Chongqing Municipality
    • Wanzhou, Chongqing Municipality, China, 404199
      • Chongqing University Three Gorges Hospital ( Site 4516)
  • Fujian
    • Fuzhou, Fujian, China, 350014
      • Fujian Provincial Cancer Hospital ( Site 4517)
  • Guangdong
    • Guangzhou, Guangdong, China, 510515
      • Southern Medical University Nanfang Hospital-Depatrment of Respiratory and Critical Care Medicine ( Site 4519)
    • Jiangmen, Guangdong, China, 529030
      • Jiangmen Center Hospital ( Site 4509)
    • Shenzhen, Guangdong, China, 518020
      • ShenZhen People's Hospital ( Site 4504)
  • Hubei
    • Wuhan, Hubei, China, 430048
      • Union Hospital Tongji Medical College Huazhong University of Science and Technology-Medical Oncology ( Site 4502)
  • Jiangxi
    • Nanchang, Jiangxi, China, 330006
      • The First Affiliated Hospital of Nanchang University-Respiratory Medicine Department ( Site 4515)
  • Shaanxi
    • Xi'an, Shaanxi, China, 710061
      • The First Affiliated Hospital of Xi'an Jiaotong University ( Site 4520)
  • Shanghai Municipality
    • Shanghai, Shanghai Municipality, China, 200032
      • Fudan University Shanghai Cancer Center-Oncology ( Site 4512)
  • Shanxi
    • Taiyuan, Shanxi, China, 410013
      • Shanxi Cancer Hospital ( Site 4521)
  • Tianjin Municipality
    • Tianjin, Tianjin Municipality, China, 300051
      • Tianjin Chest Hospital ( Site 4518)
  • Zhejiang
    • Hangzhou, Zhejiang, China, 310003
      • The First Affiliated Hospital, Zhejiang University-Respiratory Department ( Site 4514)
    • Linhai, Zhejiang, China, 317000
      • Taizhou Hospital of Zhejiang Province ( Site 4508)
• France
  • Paris, France, 75014
    • Hopitaux Universitaires Paris Centre-Hopital Cochin ( Site 2603)
  • Finistere
    • Quimper, Finistere, France, 29107
      • Centre Hospitalier de Cornouaille Quimper - Concarneau ( Site 2600)
  • Indre-et-Loire
    • Tours, Indre-et-Loire, France, 37000
      • Centre Hospitalier Régional Universitaire de Tours - Hôpital Bretonneau ( Site 2602)
• Guatemala
  • Guatemala City, Guatemala, 01009
    • MEDI-K ( Site 1403)
  • Guatemala City, Guatemala, 01010
    • Private Practice- Dr. Rixci Augusto Lenin Ramírez ( Site 1404)
  • Quetzaltenango, Guatemala, 09001
    • Centro Regional de Sub Especialidades Médicas SA ( Site 1401)
  • Quetzaltenango, Guatemala, 09002
    • Centro Medico Integral De Cancerología (CEMIC) ( Site 1400)
• Hungary
  • Budapest, Hungary, 1083
    • Semmelweis Egyetem-Pulmonológiai Klinika ( Site 2104)
  • Budapest, Hungary, 1121
    • Országos Korányi Pulmonológiai Intézet-VI. Tüdöbelosztály és Bronchológia ( Site 2100)
  • Bács-Kiskun county
    • Kecskemét, Bács-Kiskun county, Hungary, 6000
      • Bacs-Kiskun Megyei Korhaz-Onkoradiologiai Kozpont ( Site 2102)
  • Jász-Nagykun-Szolnok
    • Szolnok, Jász-Nagykun-Szolnok, Hungary, 5004
      • Jász-Nagykun-Szolnok Megyei Hetényi Géza Kórház-Onkologiai Kozpont ( Site 2103)
  • Pest County
    • Törökbálint, Pest County, Hungary, 2045
      • Reformatus Pulmonologiai Centrum ( Site 2105)
• Japan
  • Fukuoka, Japan, 810-8563
    • National Hospital Organization Kyushu Medical Center ( Site 4411)
  • Fukuoka, Japan, 811-1395
    • National Hospital Organization Kyushu Cancer Center ( Site 4410)
  • Osaka, Japan, 541-8567
    • Osaka International Cancer Institute ( Site 4407)
  • Tokyo, Japan, 113-8603
    • Nippon Medical School Hospital ( Site 4403)
  • Aichi-ken
    • Toyoake, Aichi-ken, Japan, 470-1192
      • Fujita Health University Hospital ( Site 4406)
  • Fukuoka
    • Kurume, Fukuoka, Japan, 830-0011
      • Kurume University Hospital ( Site 4412)
  • Gunma
    • Ōta, Gunma, Japan, 373-8550
      • Gunma Prefectural Cancer Center ( Site 4416)
  • Hokkaido
    • Sapporo, Hokkaido, Japan, 003-0804
      • National Hospital Organization Hokkaido Cancer Center ( Site 4415)
  • Kanagawa
    • Yokohama, Kanagawa, Japan, 236-0051
      • Kanagawa Cardiovascular and Respiratory Center ( Site 4404)
  • Miyagi
    • Natori-shi, Miyagi, Japan, 981-1293
      • Miyagi Cancer Center ( Site 4401)
    • Sendai, Miyagi, Japan, 981-0914
      • Sendai Kousei Hospital ( Site 4400)
  • Okayama-ken
    • Kurashiki, Okayama-ken, Japan, 710-8602
      • Kurashiki Central Hospital ( Site 4409)
  • Osaka
    • Hirakata, Osaka, Japan, 573-1191
      • Kansai Medical University Hospital ( Site 4408)
    • Takatsuki, Osaka, Japan, 569-8686
      • Osaka Medical and Pharmaceutical University Hospital ( Site 4414)
  • Saitama
    • Kitaadachi-gun, Saitama, Japan, 362-0806
      • Saitama Prefectural Cancer Center ( Site 4402)
  • Shizuoka
    • Sunto-gun,, Shizuoka, Japan, 411-8777
      • Shizuoka Cancer Center ( Site 4405)
  • Tochigi
    • Utsunomiya, Tochigi, Japan, 320-0834
      • Tochigi Cancer Center ( Site 4417)
  • Tokyo
    • Bunkyo-ku, Tokyo, Japan, 113-8431
      • Juntendo University Hospital ( Site 4413)
• Poland
  • Masovian Voivodeship
    • Warsaw, Masovian Voivodeship, Poland, 02-781
      • Narodowy Instytut Onkologii im. Marii Sklodowskiej-Curie - P-Klinika Nowotworow Pluca i Klatki Pier ( Site 2800)
  • Warmian-Masurian Voivodeship
    • Olsztyn, Warmian-Masurian Voivodeship, Poland, 10-357
      • Warmińsko - Mazurskie Centrum Chorób Płuc w Olsztynie-Oddzial Onkologii z Pododdzialem Chemioterapii ( Site 2802)
  • West Pomeranian Voivodeship
    • Koszalin, West Pomeranian Voivodeship, Poland, 75-581
      • Szpital Wojewódzki im. Mikoaja Kopernika w Koszalinie-Oddzial Dzienny Chemioterapii ( Site 2801)
• Romania
  • Cluj-Napoca, Romania, 400015
    • Institutul Oncologic-Oncologie Medicala ( Site 2302)
  • Cluj
    • Florești, Cluj, Romania, 407280
      • SC Radiotherapy Center Cluj SRL-Oncologie Medicala ( Site 2303)
  • Dolj
    • Craiova, Dolj, Romania, 200542
      • Centrul de Oncologie Sfantul Nectarie-Medical ( Site 2301)
  • Timiș County
    • Timișoara, Timiș County, Romania, 300239
      • Cabinet Medical Oncomed ( Site 2305)
• South Africa
  • Eastern Cape
    • Port Elizabeth, Eastern Cape, South Africa, 6055
      • CANCERCARE LANGENHOVEN DRIVE ONCOLOGY CENTRE ( Site 2903)
  • Gauteng
    • Johannesburg, Gauteng, South Africa, 2196
      • Medical Oncology Centre of Rosebank ( Site 2907)
    • Pretoria, Gauteng, South Africa, 0001
      • Steve Biko Academic Hospital-Medical Oncology ( Site 2904)
    • Sandton, Gauteng, South Africa, 2196
      • Sandton Oncology Medical Group (Pty) Ltd-Research ( Site 2900)
  • KwaZulu-Natal
    • Durban, KwaZulu-Natal, South Africa, 4091
      • The Oncology Centre ( Site 2901)
  • Western Cape
    • Cape Town, Western Cape, South Africa, 7570
      • Cape Town Oncology Trials ( Site 2902)
• Spain
  • Barcelona, Spain, 08035
    • Hospital Universitari Vall d'Hebron-Oncology ( Site 2400)
  • Huelva, Spain, 21005
    • Hospital Universitario Juan Ramon Jimenez-Oncología Medica ( Site 2402)
  • La Coruna
    • Santiago de Compostela, La Coruna, Spain, 15706
      • CHUS - Hospital Clinico Universitario-Servicio de Oncologia ( Site 2404)
  • Madrid, Comunidad de
    • Madrid, Madrid, Comunidad de, Spain, 28009
      • HOSPITAL GENERAL UNIVERSITARIO GREGORIO MARAÑON-ONCOLOGY ( Site 2401)
• Taiwan
  • Changhua, Taiwan, 50006
    • Changhua Christian Hospital ( Site 4203)
  • Kaohsiung City, Taiwan, 807
    • Kaohsiung Medical University Chung-Ho Memorial Hospital ( Site 4207)
  • Kaohsiung City, Taiwan, 82445
    • E-Da hospital ( Site 4208)
  • Kaohsiung City, Taiwan, 83301
    • Chang Gung Memorial Hospital at Kaohsiung ( Site 4200)
  • Tainan City, Taiwan, 704
    • National Cheng Kung University Hospital ( Site 4202)
  • Taipei, Taiwan, 10002
    • National Taiwan University Hospital-Oncology ( Site 4204)
  • Taipei
    • Taipei City, Taipei, Taiwan, 106
      • National Taiwan University Cancer Center (NTUCC) ( Site 4205)
• Thailand
  • Chiang Mai, Thailand, 50200
    • Maharaj Nakorn Chiang Mai Hospital ( Site 4300)
  • Bangkok
    • Bangkok, Bangkok, Thailand, 10330
      • Chulalongkorn University ( Site 4301)
    • Bangkok, Bangkok, Thailand, 10700
      • Division of Medical Oncology, Siriraj H ( Site 4303)
  • Changwat Songkhla
    • Songkhla, Changwat Songkhla, Thailand, 90110
      • Songklanagarind hospital ( Site 4302)
• Turkey (Türkiye)
  • Ankara, Turkey (Türkiye), 06010
    • Gulhane Egitim Arastirma Hastanesi-Oncology ( Site 2504)
  • Ankara, Turkey (Türkiye), 06230
    • Hacettepe Universite Hastaneleri-oncology hospital ( Site 2506)
  • Ankara, Turkey (Türkiye), 06800
    • Ankara City Hospital-Medical Oncology ( Site 2501)
  • Istanbul, Turkey (Türkiye), 34722
    • TC Saglik Bakanligi Goztepe Prof. Dr. Suleyman Yalcin Sehir Hastanesi-oncology ( Site 2502)
  • Izmir, Turkey (Türkiye), 35575
    • I.E.U. Medical Point Hastanesi-Oncology ( Site 2507)
  • Kayseri, Turkey (Türkiye), 38010
    • Memorial Kayseri Hastanesi ( Site 2500)
  • Malatya, Turkey (Türkiye), 44280
    • İnönü Üniversitesi Turgut Özal Tıp Merkezi-medical oncology depertmant ( Site 2503)
• United States
  • Arizona
    • Phoenix, Arizona, United States, 85004
      • St. Joseph's Hospital and Medical Center-Dignity Health Cancer Institute ( Site 0023)
  • Florida
    • Clermont, Florida, United States, 34711
      • Clermont Oncology Center ( Site 0018)
    • Orange City, Florida, United States, 32763
      • Mid Florida Hematology and Oncology Center ( Site 0010)
  • Illinois
    • Chicago, Illinois, United States, 60612
      • University of Illinois at Chicago-University of Illinois Cancer Center ( Site 0022)
    • Skokie, Illinois, United States, 60077
      • Orchard Healthcare Research Inc. ( Site 0011)
  • Indiana
    • Lafayette, Indiana, United States, 47905
      • Franciscan Health Lafayette East ( Site 0020)
  • Kentucky
    • Paducah, Kentucky, United States, 42003
      • Mercy Health-Paducah Cancer Center ( Site 0006)
  • Mississippi
    • Hattiesburg, Mississippi, United States, 39401
      • Hattiesburg Clinic Hematology/Oncology ( Site 0008)
  • Missouri
    • Bolivar, Missouri, United States, 65613
      • Central Care Cancer Center - Bolivar ( Site 0017)

Participation Criteria

Eligibility Criteria

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

Description

The key inclusion and exclusion criteria include but are not limited to the following:

Inclusion Criteria:

• Has histologically or cytologically confirmed diagnosis of squamous or non-squamous Non-small Cell Lung Cancer (NSCLC)
• Must provide archival tumor tissue sample or newly obtained core, incisional, or excisional biopsy of a tumor lesion not previously irradiated
• Has a life expectancy of at least 3 months

Exclusion Criteria:

• Has a diagnosis of small cell lung cancer or, for mixed tumors, presence of small cell elements
• Has received prior systemic anticancer therapy for metastatic NSCLC
• Has received prior systemic anticancer therapy including investigational agents within 4 weeks before randomization
• Has received prior radiotherapy within 2 weeks of start of study intervention or has radiation-related toxicity requiring corticosteroids
• Has received radiation therapy to the lung (>30 Gray) within 6 months of start of study intervention
• Has received a live or live-attenuated vaccine within 30 days before the first dose of study intervention
• Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy
• Has a known additional malignancy that is progressing or has required active treatment within the past 3 years
• Has an active autoimmune disease that has required systemic treatment in past 2 years
• Has an active infection requiring systemic therapy
• Has a history of human immunodeficiency virus (HIV) infection
• Has a history of Hepatitis B or C
• Has not adequately recovered from major surgery or has ongoing surgical complications
• Has a history of 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 1: Pembrolizumab Formulated With Berahyaluronidase Alfa + Platinum Doublet Chemotherapy; Participants with treatment-naïve metastatic NSCLC receive 790 mg of Pembrolizumab Formulated With Berahyaluronidase Alfa via subcutaneous (SC) injection on Day 1 of each 6-week cycle for 18 cycles (up to approximately 108 weeks) in combination with platinum doublet chemotherapy.	Drug: Pemetrexed; Pemetrexed 500 mg/m² by IV Infusion will be administered for nonsquamous NSCLC as per the schedule specified in arm.; Other Names: Alimta; Drug: Cisplatin; Cisplatin 75 mg/m² by IV Infusion will be administered for nonsquamous and squamous NSCLC as per the schedule specified in arm.; Other Names: Platinol-AQ; Drug: Carboplatin; Carboplatin AUC 5 mg/mL/min in nonsquamous and AUC 6 mg/mL/min in squamous NSCLC will be administered as per the schedule specified in arm.; Drug: Paclitaxel; Paclitaxel 200 mg/m² by IV Infusion will be administered for squamous NSCLC as per the schedule specified in arm.; Other Names: Taxol; Drug: Nab-paclitaxel; Nab-paclitaxel 100 mg/m² by IV Infusion will be administered for squamous NSCLC as per the schedule specified in arm.; Other Names: Albumin-bound paclitaxel; Drug: Filgrastim; Filgrastim will be administered as per the schedule specified for the arm.; Drug: Pegylated filgrastim; Pegylated filgrastim will be administered as per the schedule specified for the arm.; Biological: Pembrolizumab Formulated with Berahyaluronidase Alfa; Pembrolizumab (+) Berahyaluronidase alfa SC will be administered for squamous and nonsquamous NSCLC as per the schedule specified in arm; participants may be eligible for second course.; Other Names: MK-3475A
Active Comparator: Arm 2: Pembrolizumab + Platinum Doublet Chemotherapy; Participants with treatment-naïve metastatic NSCLC receive 400 mg pembrolizumab intravenous (IV) infusion in combination with platinum doublet chemotherapy.	Drug: Pemetrexed; Pemetrexed 500 mg/m² by IV Infusion will be administered for nonsquamous NSCLC as per the schedule specified in arm.; Other Names: Alimta; Drug: Cisplatin; Cisplatin 75 mg/m² by IV Infusion will be administered for nonsquamous and squamous NSCLC as per the schedule specified in arm.; Other Names: Platinol-AQ; Drug: Carboplatin; Carboplatin AUC 5 mg/mL/min in nonsquamous and AUC 6 mg/mL/min in squamous NSCLC will be administered as per the schedule specified in arm.; Drug: Paclitaxel; Paclitaxel 200 mg/m² by IV Infusion will be administered for squamous NSCLC as per the schedule specified in arm.; Other Names: Taxol; Drug: Nab-paclitaxel; Nab-paclitaxel 100 mg/m² by IV Infusion will be administered for squamous NSCLC as per the schedule specified in arm.; Other Names: Albumin-bound paclitaxel; Biological: Pembrolizumab; Pembrolizumab by IV Infusion will be administered for squamous and nonsquamous NSCLC as per the schedule specified in arm; participants may be eligible for second course.; Other Names: MK-3475, KEYTRUDA; Drug: Filgrastim; Filgrastim will be administered as per the schedule specified for the arm.; Drug: Pegylated filgrastim; Pegylated filgrastim will be administered as per the schedule specified for the arm.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cycle 1: Area Under the Curve From Time 0 to 6 Weeks (AUC0-6 Weeks) of Pembrolizumab After the First Dose	AUC0-6 weeks was defined as a measure of pembrolizumab exposure that was calculated as the product of serum drug concentration and time from zero to 6 weeks. Blood samples were collected at pre-specified timepoints to determine AUC0-6 weeks. Per protocol, geometric mean AUC0-6 weeks value of pembrolizumab after the first dose of pembrolizumab formulated with berahyaluronidase alfa in arm 1 and after first dose of pembrolizumab in arm 2 was presented.	Cycle 1: Arm 1: Day 1: Predose and Days 2, 3, 4, 5, 6, 7, 10, 15, 29, and 42 postdose; Arm 2: Day 1: Predose and at the end of infusion, Days 4, 15, 29, and 42 postdose (cycle length = 42 days)
Cycle 3: Trough Serum Concentration (Ctrough) of Pembrolizumab at Steady State	Ctrough was defined as the lowest serum concentration of pembrolizumab reached at steady state. Blood samples were collected at pre-specified timepoints for the determination of Ctrough. Per protocol, geometric mean Ctrough value of pembrolizumab at steady state of pembrolizumab formulated with berahyaluronidase alfa in arm 1 and of pembrolizumab in arm 2 was presented.	Cycle 3: Arm 1: Day 1: Predose and Days 4, 10, and 42 postdose; Arm 2: Day 1: Predose and at the end of infusion, Days 4 and 42 postdose (cycle length = 42 days)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cycle 1: Maximum Serum Concentration (Cmax) of Pembrolizumab After the First Dose	Cmax was defined as the maximum serum concentration of pembrolizumab reached after first dose. Blood samples were collected at pre-specified timepoints for the determination of Cmax. Per protocol, geometric mean Cmax value of pembrolizumab after the first dose of pembrolizumab formulated with berahyaluronidase alfa in arm 1 and after first dose of pembrolizumab in arm 2 was presented.	Cycle 1: Arm 1: Day 1: Predose and Days 2, 3, 4, 5, 6, 7, 10, 15, 29, and 42 postdose; Arm 2: Day 1: Predose and at the end of infusion, Days 4, 15, 29, and 42 postdose (cycle length = 42 days)
Cycle 1: Trough Serum Concentration (Ctrough) of Pembrolizumab After the First Dose	Ctrough was defined as the lowest serum concentration of pembrolizumab reached after first dose. Blood samples were collected at pre-specified timepoints for the determination of Ctrough. Per protocol, geometric mean Ctrough value of pembrolizumab after the first dose of pembrolizumab formulated with berahyaluronidase alfa in arm 1 and after first dose of pembrolizumab in arm 2 was presented.	Cycle 1: Arm 1: Day 1: Predose and Days 2, 3, 4, 5, 6, 7, 10, 15, 29, and 42 postdose; Arm 2: Day 1: Predose and at the end of infusion, Days 4, 15, 29, and 42 postdose (cycle length = 42 days)
Cycle 3: Area Under the Curve From Time 0 to 6 Weeks (AUC0-6 Weeks) of Pembrolizumab at Steady State	AUC0-6 weeks was defined as a measure of pembrolizumab exposure that was calculated as the product of serum drug concentration and time from zero to 6 weeks. Blood samples were collected at pre-specified timepoints to determine AUC0-6 weeks. Per protocol, geometric mean AUC0-6 weeks value of pembrolizumab at steady state of pembrolizumab formulated with berahyaluronidase alfa in arm 1 and pembrolizumab in arm 2 was presented.	Cycle 3: Arm 1: Day 1: Predose and Days 4, 10, and 42 postdose; Arm 2: Day 1: Predose and at the end of infusion, Days 4 and 42 postdose (cycle length = 42 days)
Cycle 3: Maximum Serum Concentration (Cmax) of Pembrolizumab at Steady State	Cmax was defined as the maximum serum concentration of pembrolizumab reached at steady state. Blood samples were collected at pre-specified timepoints to determine Cmax. Per protocol, geometric mean Cmax value of pembrolizumab at steady state of pembrolizumab formulated with berahyaluronidase alfa in arm 1 and pembrolizumab in arm 2 was presented.	Cycle 3: Arm 1: Day 1: Predose and Days 4, 10, and 42 postdose; Arm 2: Day 1: Predose and at the end of infusion, Days 4 and 42 postdose (cycle length = 42 days)
Number of Participants Who Test Positive for Anti-Drug Antibodies (ADAs) for Pembrolizumab	Blood samples were collected at designated time points for the determination of the presence or absence of anti-pembrolizumab antibodies. Per protocol, the number of participants who developed anti pembrolizumab antibodies were reported.	Predose and Postdose on Day 1 of Cycles 1 through 18 (up to approximately 28 months). Each cycle is 6 weeks.
Objective Response Rate (ORR)	ORR was defined as the percentage of participants with 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 Response Evaluation Criteria In Solid Tumors Version 1.1 (RECIST 1.1). The percentage of participants who experienced CR or PR as assessed by Blinded Independent Central Review (BICR) were presented.	Up to approximately 28 months
Progression-free Survival (PFS)	PFS was defined as the time from randomization to the first documented progressive disease (PD) or death due to any cause, whichever occurs first as assessed by RECIST 1.1. 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. PFS as assessed by BICR were presented.	Up to approximately 28 months
Overall Survival (OS)	OS was defined as the time from randomization to death due to any cause.	Up to approximately 28 months
Duration of Response (DOR)	For participants who demonstrated a 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, DOR is defined as the time from first documented evidence of CR or PR until PD or death. Per RECIST 1.1, 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. DOR as assessed by BICR were presented.	Up to approximately 28 months
Number of Participants Who Experienced at Least One Adverse Event (AE)	An AE was 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. The number of participants who experienced at least one AE were reported .	Up to approximately 28 months
Number of Participants Who Discontinued Study Treatment Due to 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. The number of participants who discontinue study treatment due to an AE will be reported for Arms 1 and 2.	Up to approximately 28 months
Change From Baseline in European Organization for Research and Treatment (EORTC) Quality of Life Questionnaire-Core30 (QLQ-C30) Combined Global Health Status/Quality of Life (Items 29 & 30) Scale Combined Score	EORTC QLQ-C30 is a questionnaire to assess the overall quality of life (QoL) of cancer patients. Participant responses to questions regarding Global Health Status (GHS; "How would you rate your overall health during the past week?") and QoL ("How would you rate your overall quality of life during the past week?") are scored on a 7-point scale (1= Very poor to 7=Excellent). The combined score of GHS (Item 29) and QoL (Item 30) is computed by averaging the raw scores of the 2 items and then applying a linear transformation to standardize the average score, so that the combined scores range from 0-100. A higher score indicates a better outcome. Per protocol, the change from baseline in GHS and QoL combined score was presented.	Baseline and Week 24
Change From Baseline in Physical Functioning (EORTC-QLQ-C30 Items 1-5) Score	EORTC QLQ-C30 is a questionnaire to assess the overall QoL of cancer patients. Participant responses to 5 questions about their physical functioning (Items 1 to 5) are scored on a 4-point scale (1=Not at All to 4=Very Much). The combined score of items 1 to 5 was computed by averaging the raw scores of the 5 items and then applying a linear transformation to standardize the average score, so that the combined scores range from 0-100. A higher score indicates a better outcome. Per protocol, the change from baseline in EORTC QLQ-C30 physical functioning (Items 1-5) combined score was presented.	Baseline and Week 24
Change From Baseline in the European Organization for the Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire C30 (QLQ-C30) Role Functioning Score-Items 6 and 7	EORTC QLQ-C30 is a questionnaire to assess the overall QoL of cancer patients. Participant responses to the questions "Were you limited in doing either your work or other daily activities during the past week?" and "Were you limited in pursuing your hobbies or other leisure time activities during the past week?" will be scored on a 4-point scale (1=Not at All to 4=Very Much). The combined score of items 1 to 5 was computed by averaging the raw scores of the 2 items and then applying a linear transformation to standardize the average score, so that the combined scores range from 0-100. Higher scores indicate a better level of role functioning. Change from baseline in the EORTC QLQ-C30 role functioning (Items 6-7) combined score was presented.	Baseline and Week 24

Collaborators and Investigators

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

Publications and helpful links

General Publications

• Felip E, Rojas CI, Schenker M, Kowalski DM, Casarini IA, Csoszi T, Sendur MAN, Martins J, Calles Blanco A, Wang CC, Wang M, Ramirez Fallas RAL, Yoshioka H, Nair S, Song X, Deng X, Lala M, Eiras R, Takahashi T. Subcutaneous versus intravenous pembrolizumab, in combination with chemotherapy, for treatment of metastatic non-small-cell lung cancer: the phase III 3475A-D77 trial. Ann Oncol. 2025 Jul;36(7):775-785. doi: 10.1016/j.annonc.2025.03.012. Epub 2025 Mar 27.

Helpful Links

• Merck Clinical Trials Information
• Plain Language Summary

Study record dates

Study Major Dates

• Study Start (Actual): February 14, 2023
• Primary Completion (Actual): July 12, 2024
• Study Completion (Estimated): May 22, 2028

Study Registration Dates

• First Submitted: January 27, 2023
• First Submitted That Met QC Criteria: January 27, 2023
• First Posted (Actual): February 10, 2023

Study Record Updates

• Last Update Posted (Estimated): September 11, 2025
• Last Update Submitted That Met QC Criteria: September 9, 2025
• Last Verified: September 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Respiratory Tract Diseases; Lung Diseases; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Carcinoma, Non-Small-Cell Lung; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Organic Chemicals; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Hydrocarbons; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Terpenes; Biological Factors; Carbohydrates; Inorganic Chemicals; Chlorine Compounds; Nitrogen Compounds; Coordination Complexes; Guanine; Hypoxanthines; Purinones; Purines; Glutamates; Amino Acids, Acidic; Amino Acids; Amino Acids, Dicarboxylic; Taxoids; Cyclodecanes; Diterpenes; Intercellular Signaling Peptides and Proteins; Glycoproteins; Glycoconjugates; Platinum Compounds; Colony-Stimulating Factors; Hematopoietic Cell Growth Factors; Cytokines; Albumins; Granulocyte Colony-Stimulating Factor; Albumin-Bound Paclitaxel; Pemetrexed; Carboplatin; Paclitaxel; Cisplatin; pembrolizumab; 130-nm albumin-bound paclitaxel; Filgrastim
• Other Study ID Numbers: 3475A-D77; 2022-501506-36-00 (Other Identifier: EU CT); MK-3475A-D77 (Other Identifier: MSD); jRCT2031230049 (Other Identifier: Japan Registry of Clinical Trials (jRCT)); U1111-1280-9384 (Registry Identifier: UTN)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: https://trialstransparency.msdclinicaltrials.com/pdf/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