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)
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.
Eligibility
Sex
ALL
Min age
18 Years
Max age
—
Healthy volunteers
No
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
Primary outcome measure(s)
Cycle 1 Area Under The Curve From 0-3 Weeks (AUC 0-3wks) of Pembrolizumab — 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 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 6 Model-Based Minimal Concentration (Ctrough) of Pembrolizumab — 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. 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.
Trial sites (126)
Facility
City
Region
Status
St. Bernards Medical Center ( Site 0103)
Jonesboro
Arkansas
St Joseph Heritage Healthcare-Oncology ( Site 0102)
Fullerton
California
Cancer Blood and Specialty Clinic ( Site 0105)
Los Alamitos
California
PIH Health Hematology Medical Oncology ( Site 0106)
Whittier
California
Holy Cross Hospital ( Site 0017)
Fort Lauderdale
Florida
Memorial Regional Hospital-Memorial Cancer Institute ( Site 0104)
Hollywood
Florida
Advent Health ( Site 0013)
Orlando
Florida
Fort Wayne Medical Oncology and Hematology ( Site 0101)
Fort Wayne
Indiana
Baptist Health Lexington ( Site 0099)
Lexington
Kentucky
St Luke's Hospital - Kansas City ( Site 0033)
Kansas City
Missouri
St. Vincent Frontier Cancer Center ( Site 0058)
Billings
Montana
Montefiore Medical Center [Bronx, NY] ( Site 0040)
The Bronx
New York
The University of Tennessee Medical Center ( Site 0050)
Knoxville
Tennessee
Tennessee Oncology ( Site 0051)
Nashville
Tennessee
Oncology Consultants, PA ( Site 0052)
Houston
Texas
Millennium Physicians - Oncology ( Site 0097)
Houston
Texas
Oncology & Hematology Assoc. SW Virginia, Inc., DBA Blue Ridge Cancer Care ( Site 0100)
Blacksburg
Virginia
West Virginia University ( Site 0056)
Morgantown
West Virginia
HOSPITAL EVANGÉLICO DE CACHOEIRO DE ITAPEMIRIM ( Site 0307)
Cachoeiro de Itapemirim
Espírito Santo
Hospital Sao Vicente de Paulo ( Site 0311)
Passo Fundo
Rio Grande do Sul
Instituto Joinvilense de Hematologia e Oncologia ( Site 0308)
Joinville
Santa Catarina
Fundacao Faculdade Regional de Medicina de Sao Jose do Rio Preto ( Site 0305)
São José do Rio Preto
São Paulo
Núcleo de Pesquisa Clínica da Rede São Camilo ( Site 0304)
São Paulo
São Paulo
Nouvel Hôpital Civil (NHC) ( Site 1018)
Strasbourg
Bas-Rhin
CHU Limoges CHU Dupuytren ( Site 1011)
Limoges
Haute-Vienne
Hôpital Foch ( Site 1019)
Suresnes
Hauts-de-Seine
Institut Regional du Cancer de Montpellier - ICM ( Site 1003)
Montpellier
Herault
Centre Hospitalier Sud Réunion ( Site 1020)
Saint-Pierre
La Reunion
Hopital Guillaume & Rene Laennec ( Site 1007)
Saint-Herblain
Loire-Atlantique
Centre Hospitalier de Pau ( Site 1016)
Pau
Pyrenees-Atlantiques
CHU de Rouen ( Site 1013)
Rouen
Seine-Maritime
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
Petz Aladar Megyei Oktato Korhaz ( Site 1110)
Győr
Győr-Moson-Sopron
Jasz Nagykun Szolnok Megyei Hetenyi Geza Korhaz Rendelointezet ( Site 1103)
Szolnok
Jász-Nagykun-Szolnok
+ 86 more sites — see the full list on the official registry below.
This page summarises publicly available registry data for informational purposes — not medical advice. Eligibility is determined by each study team; patients should discuss participation with their clinician.
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