Efficacy and Safety of Pembrolizumab (MK-3475) With Platinum Doublet Chemotherapy as Neoadjuvant/Adjuvant Therapy for Participants With Resectable Stage II, IIIA, and Resectable IIIB (T3-4N2) Non-small Cell Lung Cancer (MK-3475-671/KEYNOTE-671)
Non-small Cell Lung Cancer

About this trial
This is an interventional treatment trial for Non-small Cell Lung Cancer
Eligibility Criteria
Inclusion Criteria:
- Have previously untreated and pathologically confirmed resectable Stage II, IIIA, or IIIB (N2) NSCLC.
- Be able to undergo protocol therapy, including necessary surgery. A positron emission tomography (PET) scan may be utilized as a surrogate for pathologic staging of N1 lymph nodes for participants with T2b and T4 tumors.
- If male, must agree to use contraception or practice abstinence as well as refrain from donating sperm during the treatment period and for the time needed to eliminate each study intervention after the last dose of study intervention.
- If female, may participate if not pregnant or breastfeeding, and at least one of the following conditions apply: 1) not a woman of childbearing potential (WOCBP); or 2) a WOCBP who agrees to follow contraceptive guidance during the treatment period and for the time needed to eliminate each study intervention after the last dose of study intervention and agrees not to donate eggs (ova, oocytes) to others or freeze/store for her own use for the purpose of reproduction during this period.
- Have available formalin-fixed paraffin embedded (FFPE) tumor tissue sample blocks for submission. If blocks are not available, have unstained slides for submission for central programmed death-ligand 1 (PD-L1) testing.
- Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1 within 10 days of randomization.
- Have adequate organ function.
Exclusion Criteria:
- Has one of the following tumor locations/types:1) NSCLC involving the superior sulcus; 2) Large cell neuro-endocrine cancer (LCNEC); or 3) Sarcomatoid tumor.
- Has a history of (non-infectious) pneumonitis /interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease that requires steroids.
- Has an active infection requiring systemic therapy.
- Has had an allogenic tissue/sold organ transplant.
- Has a known severe hypersensitivity (≥ Grade 3) to pembrolizumab, its active substance and/or any of its excipients.
- Has a known severe hypersensitivity (≥ Grade 3) to any of the study chemotherapy agents and/or to any of their excipients.
- Has an active autoimmune disease that has required systemic treatment in past 2 years.
- Has a known history of human immunodeficiency virus (HIV) infection.
- Has a known history of Hepatitis B or Hepatitis C.
- Has a known history of active tuberculosis.
- Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the participant's participation for the full duration of the trial, or is not in the best interest of the participant to participate.
- Has known psychiatric or substance abuse disorders that would interfere with cooperating with the requirements of the trial.
- Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent or with an agent directed to another co-inhibitory T-cell receptor.
- Has received prior systemic anti-cancer therapy including investigational agents for the current malignancy prior to randomization/allocation.
- Has received prior radiotherapy within 2 weeks of start of trial treatment.
- Has received a live vaccine within 30 days prior to the first dose of trial drug.
- Is currently participating in or has participated in a trial of an investigational agent or has used an investigational device within 4 weeks prior to the first dose of trial treatment.
- Has a diagnosis of immunodeficiency or is receiving either systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior the first dose of trial drug.
- Has a known additional malignancy that is progressing or requires active treatment within the past 5 years.
Sites / Locations
- Banner MD Anderson Cancer Center ( Site 0028)
- Western Regional Medical Center, Inc. ( Site 0050)
- University of Arizona Cancer Center - Dignity Health ( Site 0062)
- University of Arizona Cancer Center ( Site 0012)
- Pacific Cancer Medical Center, Inc. ( Site 0004)
- Providence Saint Joseph Medical Center ( Site 0061)
- Pacific Cancer Care ( Site 0035)
- John Wayne Cancer Institute ( Site 0049)
- St Joseph Heritage Healthcare ( Site 0040)
- Stanford University, Stanford Cancer Center ( Site 0046)
- Hartford Hospital ( Site 0069)
- Helen F. Graham Cancer Center & Research Institute ( Site 0015)
- Mayo Clinic Jacksonville ( Site 0022)
- Miami Cancer Institute-Baptist Hospital ( Site 0068)
- Southeastern Regional Medical Center ( Site 0051)
- Northwest Oncology and Hematology ( Site 0001)
- Ingalls Memorial Hospital ( Site 0044)
- PPG-Oncology ( Site 0043)
- University of Iowa Hospital and Clinics ( Site 0010)
- Ashland-Bellefonte Cancer Center ( Site 0021)
- Harry & Jeanette Weinberg Cancer Institute ( Site 0081)
- Boston Medical Center ( Site 0057)
- UMass Memorial Medical Center ( Site 0030)
- Henry Ford Health System ( Site 0031)
- Herbert Herman Cancer Center, Sparrow Hospital ( Site 0034)
- Mayo Clinic ( Site 0026)
- St. Vincent Healthcare Frontier Cancer Center ( Site 0005)
- University of Nebraska Medical Center ( Site 0047)
- Memorial Sloan Kettering Cancer Center Basking Ridge ( Site 0074)
- Memorial Sloan Kettering Cancer Center- Monmouth ( Site 0077)
- MSKCC-Bergen ( Site 0075)
- St. Peter's Hospital Cancer Care Center ( Site 0039)
- Montefiore Einstein Center ( Site 0016)
- Memorial Sloan-Kettering Cancer Center at Commack ( Site 0076)
- Memorial Sloan Kettering Cancer Center Westchester ( Site 0079)
- Memorial Sloan Kettering Cancer Center ( Site 0060)
- Stony Brook University Medical Center - Cancer Center ( Site 0019)
- Memorial Sloan Kettering Cancer Center - Nassau ( Site 0078)
- White Plains Hospital Center for Cancer Care ( Site 0007)
- Southwestern Regional Medical Center, Inc. ( Site 0054)
- OHSU Center for Health & Healing ( Site 1006)
- UPMC Pinnacle Health System - East Location ( Site 0063)
- Cancer Treatment Centers of America-Eastern Regional Medical Center ( Site 0053)
- Allegheny General Hospital ( Site 0009)
- UPMC Hillman Cancer Centers ( Site 0041)
- VA Pittsburgh Healthcare System ( Site 0052)
- Saint Francis Cancer Center ( Site 0096)
- Emily Couric Clinical Cancer Center ( Site 0013)
- Inova Schar Cancer Institute ( Site 0032)
- Virginia Cancer Specialists, PC ( Site 0080)
- Providence Regional Cancer Partnership ( Site 0065)
- Centro de Oncologia e Investigacion Buenos Aires COIBA ( Site 0136)
- Hospital Privado de Comunidad. ( Site 0130)
- Hospital Universitario Austral ( Site 0127)
- Fundacion Favaloro ( Site 0128)
- Sanatorio Britanico ( Site 0125)
- Sanatorio Parque ( Site 0135)
- Hospital Provincial del Centenario ( Site 0131)
- Hospital Privado Universitario de Córdoba ( Site 0139)
- Sanatorio Allende ( Site 0129)
- CER San Juan Centro Polivalente de Asistencia e Investigacion Clinica ( Site 0133)
- Orange Health Services ( Site 0624)
- Westmead Hospital ( Site 0621)
- AZ Sint-Maarten ( Site 0226)
- Centre Hospitalier Universitaire de Liège - Domaine Universitaire du Sart Tilman ( Site 0223)
- UZ Gent ( Site 0224)
- AZ Nikolaas ( Site 0225)
- UZ Leuven ( Site 0221)
- AZ Delta ( Site 0222)
- Centro Regional Integrado de Oncologia ( Site 0160)
- Instituto do Cancer do Ceara ( Site 0152)
- Sirio-Libanes Brasilia - Centro de Oncologia - Asa Sul ( Site 0159)
- Liga Norte Riograndense Contra o Cancer ( Site 0150)
- Hospital de Caridade de Ijui ( Site 0153)
- Uniao Brasileira de Educacao e Assistencia Hospital Sao Lucas da Pucrs ( Site 0146)
- Hospital Nossa Senhora da Conceicao ( Site 0145)
- YNOVA Pesquisa Clinica ( Site 0823)
- Fundacao Pio XII - Hospital de Cancer de Barretos ( Site 0144)
- Instituto Nacional do Cancer Jose Alencar Gomes da Silva INCA ( Site 0149)
- Hospital Paulistano - Amil Clinical Research ( Site 0822)
- Hospital Alemao Oswaldo Cruz ( Site 0158)
- Princess Margaret Cancer Centre ( Site 0109)
- CIUSSS du Saguenay-Lac-St-Jean ( Site 0101)
- Centre Hospitalier de l Universite de Montreal - CHUM ( Site 0110)
- CIUSSS Ouest de l Ile - St-Mary s Hospital ( Site 0104)
- McGill University Health Centre ( Site 0111)
- Tianjin Medical University General Hospital ( Site 0806)
- Beijing Cancer Hospital ( Site 0810)
- Beijing Cancer Hospital ( Site 0811)
- Cancer Hospital Chinese Academy of Medical Sciences ( Site 0801)
- Peking University Third Hospital ( Site 0812)
- Peking Union Medical College Hospital ( Site 0809)
- Sun Yat-Sen University Cancer Center ( Site 0816)
- Hunan Cancer Hospital ( Site 0815)
- Fudan University Shanghai Cancer Center ( Site 0813)
- Zhongshan Hospital of Fudan University ( Site 0808)
- Shanghai Pulmonary Hospital-Thoracic Surgery department ( Site 0817)
- Tang Du Hospital ( Site 0803)
- The First Affiliated Hospital of Zhejiang University ( Site 0804)
- Zhejiang Cancer Hospital.... ( Site 0814)
- Hwa Mei Hospital University of Chinese Academy of Sciences ( Site 0802)
- SA Pohja-Eesti Regionaalhaigla ( Site 1100)
- Hopital Foch ( Site 0243)
- Nouvel Hopital Civil ( Site 0255)
- CHU de Toulouse - Hopital Larrey ( Site 0258)
- Clinique Francois Chenieux ( Site 0246)
- Hospices Civils de Lyon Centre Hospitalier Lyon Sud ( Site 0241)
- Centre Hospitalier Metropole Savoie Site de Chambery ( Site 0245)
- Centre Hospitalier Annecy Genevois ( Site 0242)
- CHU de Rouen ( Site 0252)
- Hôpital Avicenne - Service d oncologie medicale ( Site 0249)
- H.I.A. Sainte-Anne ( Site 0251)
- Institut Curie ( Site 0250)
- Klinikum Esslingen GmbH ( Site 0875)
- LKI Lungenfachklinik Immenhausen ( Site 0268)
- Florence Nightingale Krankenhaus ( Site 0874)
- Lungenklinik Hemer ( Site 0269)
- Mathias Spital Rheine ( Site 0261)
- Katholisches Klinikum Koblenz Haus Marienhof ( Site 0873)
- Universitaetsklinikum Carl Gustav Carus ( Site 0273)
- Universitaetsklinikum Leipzig AOeR ( Site 0277)
- LungenClinic Grosshansdorf GmbH ( Site 0267)
- Universitaetsklinikum Schleswig Holstein ( Site 0871)
- Zentralklinik Bad Berka GmbH ( Site 0264)
- SRH Waldklinikum Gera GmbH ( Site 0272)
- Evangelische Lungenklinik Berlin ( Site 0274)
- HELIOS Klinikum Emil von Behring ( Site 0280)
- Asklepios Klinikum Hamburg ( Site 0271)
- Cork University Hospital ( Site 0452)
- St James Hospital ( Site 0451)
- Mid Western Cancer Centre ( Site 0450)
- Istituto Nazionale Tumori ( Site 0309)
- Azienda Ospedaliera dei Colli V. Monaldi ( Site 0301)
- IRST-Istituto Scientifico Romagnolo per lo Studio e la cura dei Tumori ( Site 0300)
- Istituto Clinico Humanitas Research Hospital ( Site 0314)
- ASST Grande Ospedale Metropolitano Niguarda-Oncologia Falck ( Site 0315)
- Azienda Ospedaliera San Gerardo ( Site 0308)
- AOU San Luigi Gonzaga di Orbassano ( Site 0313)
- Azienda Ospedaliera Spedali Civili di Brescia ( Site 0307)
- IRCCS Ospedale San Raffaele di Milano ( Site 0303)
- Azienda Ospedaliera San Camillo Forlanini ( Site 0311)
- Aichi Cancer Center Hospital ( Site 0765)
- National Cancer Center Hospital East ( Site 0761)
- HP of the Univ. of Occupational and Environmental Health, Japan ( Site 0770)
- Hyogo Cancer Center ( Site 0764)
- St. Marianna University School of Medicine Hospital ( Site 0769)
- Kanagawa Cancer Center ( Site 0763)
- Oita University Hospital ( Site 0766)
- Fukushima Medical University Hospital ( Site 0772)
- Hiroshima University Hospital ( Site 0762)
- National Cancer Center Hospital ( Site 0767)
- Juntendo University Hospital ( Site 0768)
- Tokyo Medical University Hospital ( Site 0771)
- National Cancer Center ( Site 0702)
- The Catholic University of Korea St. Vincent s Hospital ( Site 0705)
- Asan Medical Center ( Site 0701)
- Samsung Medical Center ( Site 0704)
- SMG-SNU Boramae Medical Center ( Site 0707)
- Pauls Stradins Clinical University Hospital ( Site 0911)
- Riga East Clinical University Hospital ( Site 0912)
- LSMUL Kauno Klinikos ( Site 0932)
- Nacionalinis Vezio Institutas ( Site 0931)
- Sarawak General Hospital ( Site 0782)
- University Malaya Medical Centre ( Site 0781)
- Centrum Pulmonologii i Torakochirurgii w Bystrej ( Site 0484)
- Dolnoslaskie Centrum Onkologii. ( Site 0491)
- Centrum Onkologii im. Prof. Franciszka Lukaszczyka ( Site 0488)
- Wojewodzki Szpital Specjalistyczny im. M. Kopernika w Lodzi ( Site 0493)
- Szpital Specjalistyczny w Prabutach Sp. z o.o. ( Site 0483)
- Wielkopolskie Centrum Pulmonologii i Torakochirurgii ( Site 0487)
- S C Pelican Impex SRL ( Site 0506)
- Centrul Medical Medicover Victoria ( Site 0514)
- Institutul Oncologic Prof.Dr. Ion Chiricuta Cluj-Napoca ( Site 0501)
- Institutul Oncologic Prof.Dr. Ion Chiricuta Cluj-Napoca ( Site 0515)
- SC Radiotherapy Center Cluj SRL ( Site 0509)
- S.C. Centrul de Oncologie Sf. Nectarie SRL ( Site 0504)
- S.C.R.T.C.Radiology Therapeutic Center SRL ( Site 0511)
- S C Oncocenter Oncologie Medicala S R L ( Site 0505)
- Spitalul Sf. Constantin ( Site 0512)
- Euroclinic Hospital Bucharest ( Site 0510)
- S.C.Focus Lab Plus S.R.L ( Site 0513)
- Spitalul clinic Judetean de urgenta Constanta ( Site 0508)
- Spitalul Judetean de Urgenta .Sf. Ioan cel Nou. ( Site 0503)
- Chelyabinsk Regional Clinical Oncological Dispensary ( Site 0530)
- N.N. Blokhin NMRCO ( Site 0521)
- National Medical Research Radiology Centre ( Site 0535)
- Medical Rehabilitation Center ( Site 0534)
- SBHI Leningrad Regional Clinical Hospital ( Site 0524)
- Scientific Research Oncology Institute n.a. N.N.Petrov ( Site 0533)
- Municipal Clinical Oncology Center ( Site 0523)
- Republican Clinical Oncology Dispensary of Tatarstan MoH ( Site 0529)
- Tomsk Scientific Research Institute of Oncology ( Site 0526)
- Wits Clinical Research ( Site 0570)
- Wilgers Oncology Centre ( Site 0573)
- The Oncology Centre ( Site 0571)
- Cape Town Oncology Trials Pty Ltd ( Site 0572)
- Hospital Germans Trias i Pujol. ICO de Badalona ( Site 0381)
- Instituto Catalan de Oncologia - ICO ( Site 0388)
- Hospital Universitario de Girona Doctor Josep Trueta ( Site 0386)
- Hospital Universitario Insular de Gran Canaria ( Site 0383)
- Hospital de la Santa Creu i Sant Pau ( Site 0385)
- Hospital Universitari Vall d Hebron ( Site 0389)
- Hospital General Universitario Gregorio Maranon ( Site 0382)
- Hospital Virgen del Rocio ( Site 0387)
- Kaohsiung Chang Gung Memorial Hospital ( Site 0725)
- China Medical University Hospital ( Site 0724)
- National Taiwan University Hospital ( Site 0721)
- Taipei Veterans General Hospital ( Site 0722)
- Tri-Service General Hospital ( Site 0726)
- Chang Gung Medical Foundation.Linkou Branch ( Site 0723)
- Cherkassy Regional Oncological Center ( Site 0613)
- City Clinical Hosp.4 of DCC ( Site 0607)
- MI Precarpathian Clinical Oncology Center ( Site 0603)
- MI KhRC Kherson Regional Oncology Dispensary ( Site 0614)
- PP PPC Acinus Medical and Diagnostic Centre ( Site 0609)
- National Cancer Institute of the MoH of Ukraine ( Site 0605)
- Kyiv City Clinical Oncological Center ( Site 0601)
- MI Odessa Regional Oncological Centre ( Site 0608)
- Zaporizhzhya Regional Clinical Oncology Center ( Site 0606)
- Leicester Royal Infirmary ( Site 0447)
- The Clatterbridge Cancer Centre NHS Foundation Trust ( Site 0456)
- Royal Marsden NHS Foundation Trust ( Site 0458)
- Royal Marsden Hospital ( Site 0457)
- Nottingham City Hospital Campus ( Site 0441)
- Heartlands Hospital in Birmingham ( Site 0455)
- Freeman Hospital ( Site 0444)
- Plymouth Hospitals NHS Trust ( Site 0443)
Arms of the Study
Arm 1
Arm 2
Experimental
Placebo Comparator
NAC + Neoadjuvant/Adjuvant Pembrolizumab
NAC + Neoadjuvant/Adjuvant Placebo
Neoadjuvant: Prior to surgery, participants receive up to 4 cycles (cycle length: 3 weeks) of pembrolizumab [200 mg, intravenous (IV); given on cycle day 1] in combination with platinum doublet neoadjuvant chemotherapy (NAC), consisting of cisplatin [75 mg/m^2, IV; given on cycle day 1] and either Gemcitabine [1000 mg/m^2, IV; given on cycle days 1 and 8] or Pemetrexed [500 mg/m^2, IV; given on cycle day 1]. Adjuvant: 4-12 weeks following surgery, participants receive 13 cycles (cycle length: 3 weeks) of pembrolizumab [200 mg, IV; given on cycle day 1].
Neoadjuvant: Prior to surgery, participants receive up to 4 cycles (cycle length: 3 weeks) of placebo [normal saline, IV; given on cycle day 1] in combination with platinum doublet NAC, consisting of cisplatin [75 mg/m^2, IV; given on cycle day 1] and either Gemcitabine [1000 mg/m^2, IV; given on cycle days 1 and 8] or Pemetrexed [500 mg/m^2, IV; given on cycle day 1]. Adjuvant: 4-12 weeks following surgery, participants receive 13 cycles (cycle length: 3 weeks) of placebo [normal saline, IV; given on cycle day 1].