A Trial of Pembrolizumab in Combination With Chemotherapy and Radiotherapy in Stage III NSCLC (KEYNOTE-799, MK-3475-799) (KEYNOTE-799)

A Phase 2 Trial of Pembrolizumab (MK-3475) in Combination With Platinum Doublet Chemotherapy and Radiotherapy for Participants With Unresectable, Locally Advanced Stage III Non-Small Cell Lung Cancer (NSCLC) (KEYNOTE-799)

This is a trial in adult participants with unresectable, locally advanced, Stage III non-small cell lung cancer (NSCLC) treated with pembrolizumab in combination with platinum doublet chemotherapy and standard thoracic radiotherapy followed by pembrolizumab monotherapy. The primary hypothesis of the trial is that within each platinum doublet chemotherapy cohort, the percentage of participants who develop Grade 3 or higher pneumonitis is ≤10% and estimation of objective response rate (ORR) by blinded independent central review (BICR).

Study Overview

• Status: Completed
• Conditions: Non-small Cell Lung Cancer
• Intervention / Treatment: Drug: Pembrolizumab 200 mg; Drug: Paclitaxel 45 mg/m^2; Drug: Carboplatin AUC6; Radiation: Thoracic Radiation Therapy (TRT); Drug: Paclitaxel 200 mg/m^2; Drug: Carboplatin AUC2; Drug: Cisplatin 75 mg/m^2; Drug: Pemetrexed 500 mg/m^2

• Study Type: Interventional
• Enrollment (Actual): 216
• Phase: Phase 2

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Blacktown, New South Wales, Australia, 2148
      • Blacktown Hospital Western Sydney Local Health District ( Site 0204)
    • Port Macquarie, New South Wales, Australia, 2444
      • MNCCI Port Macquarie Base Hospital ( Site 0200)
    • Wollongong, New South Wales, Australia, 2500
      • Southern Medical Day Care Centre ( Site 0201)
  • Victoria
    • Ballarat, Victoria, Australia, 3350
      • Ballarat Health Services ( Site 0206)
• France
  • Aisne
    • Saint Quentin, Aisne, France, 02321
      • C.H. de Saint Quentin ( Site 0306)
  • Bouches-du-Rhone
    • Marseille, Bouches-du-Rhone, France, 13009
      • Clinique Clairval ( Site 0311)
  • Doubs
    • Besancon, Doubs, France, 25000
      • CHU Jean Minjoz ( Site 0301)
  • Herault
    • Montpellier, Herault, France, 34298
      • Institut du Cancer de Montpellier ( Site 0300)
  • Ille-et-Vilaine
    • Rennes., Ille-et-Vilaine, France, 35033
      • C.H.R.U. de Rennes. Hopital de Pontchaillou ( Site 0302)
  • Maine-et-Loire
    • Angers, Maine-et-Loire, France, 49055
      • ICO Centre Paul Papin ( Site 0309)
  • Puy-de-Dome
    • Clermont Ferrand, Puy-de-Dome, France, 63011
      • Centre Jean Perrin ( Site 0304)
  • Somme
    • Amiens, Somme, France, 80000
      • Clinique de L'Europe ( Site 0308)
  • Val-de-Marne
    • Villejuif, Val-de-Marne, France, 94800
      • Institut de Cancerologie Gustave Roussy ( Site 0305)
• Germany
  • Berlin, Germany, 13353
    • Charite Universitaetsmedizin Berlin - Campus-Virchow-Klinikum ( Site 0414)
  • Hamburg, Germany, 22087
    • Katholisches Marienkrankenhaus gGmbH ( Site 0411)
  • Baden-Wurttemberg
    • Heidelberg, Baden-Wurttemberg, Germany, 69126
      • Thoraxklinik Heidelberg gGmbH am Universitaetsklinikum Heidelberg ( Site 0404)
    • Mannheim, Baden-Wurttemberg, Germany, 68167
      • Universitatsklinikum Mannheim GmbH ( Site 0413)
  • Nordrhein-Westfalen
    • Bochum, Nordrhein-Westfalen, Germany, 44791
      • Augusta-Kranken-Anstalt Bochum ( Site 0401)
    • Moers, Nordrhein-Westfalen, Germany, 47441
      • Bethanien Krankenhaus Moers ( Site 0406)
  • Sachsen
    • Chemnitz, Sachsen, Germany, 09113
      • Klinikum Chemnitz gGmbH ( Site 0410)
  • Schleswig-Holstein
    • Grosshansdorf, Schleswig-Holstein, Germany, 22927
      • LungenClinic Grosshansdorf GmbH ( Site 0408)
• Korea, Republic of
  • Chungcheongbuk-do [Chungbuk]
    • Cheongju si, Chungcheongbuk-do [Chungbuk], Korea, Republic of, 28644
      • Chungbuk National University Hospital ( Site 1003)
  • Kyonggi-do
    • Goyang-si, Kyonggi-do, Korea, Republic of, 10408
      • National Cancer Center ( Site 1002)
  • Seoul-teukbyeolsi [Seoul]
    • Seoul, Seoul-teukbyeolsi [Seoul], Korea, Republic of, 06351
      • Samsung Medical Center ( Site 1001)
  • Ulsan-Kwangyokshi
    • Ulsan, Ulsan-Kwangyokshi, Korea, Republic of, 44033
      • Ulsan University Hospital ( Site 1000)
• New Zealand
  • Auckland, New Zealand, 1023
    • Auckland City Hospital ( Site 0700)
• Poland
  • Kujawsko-pomorskie
    • Bydgoszcz, Kujawsko-pomorskie, Poland, 85-796
      • Centrum Onkologii im. Prof. Franciszka Lukaszczyka ( Site 0811)
  • Malopolskie
    • Krakow, Malopolskie, Poland, 31-826
      • Osrodek Badan Klinicznych przy Szpitalu Specjalistycznym ( Site 0802)
  • Mazowieckie
    • Warszawa, Mazowieckie, Poland, 02-781
      • Narodowy Instytut Onkologii im. Marii Sklodowskiej-Curie ( Site 0800)
  • Pomorskie
    • Gdynia, Pomorskie, Poland, 81-519
      • Szpital Morski im. PCK. Szpitale Pomorskie Sp. Z o.o ( Site 0812)
  • Zachodniopomorskie
    • Koszalin, Zachodniopomorskie, Poland, 75-581
      • Szpital Wojewodzki w Koszalinie im. Mikolaja Kopernika ( Site 0813)
• Russian Federation
  • Baskortostan, Respublika
    • Ufa, Baskortostan, Respublika, Russian Federation, 450054
      • Republican Clinical Oncology Dispensary of Republic of Bashkortostan ( Site 0903)
  • Moskva
    • Moscow, Moskva, Russian Federation, 115478
      • Blokhin National Medical Oncology ( Site 0902)
  • Sankt-Peterburg
    • St. Petersburg, Sankt-Peterburg, Russian Federation, 197758
      • National Medical Research Center of Oncology N.A. N.N. Petrov ( Site 0904)
  • Tatarstan, Respublika
    • Kazan, Tatarstan, Respublika, Russian Federation, 420029
      • Republican Clinical Oncology Dispensary of Tatarstan MoH ( Site 0910)
• Spain
  • Madrid, Spain, 28027
    • Clinica Universitaria de Navarra ( Site 1102)
  • Sevilla, Spain, 41009
    • Hospital Universitario Virgen Macarena ( Site 1103)
  • Barcelona [Barcelona]
    • Barcelona, Barcelona [Barcelona], Spain, 08035
      • Hospital Universitari Vall d Hebron ( Site 1101)
    • Barcelona, Barcelona [Barcelona], Spain, 08036
      • Hospital Clinic de Barcelona ( Site 1100)
  • Illes Balears [Islas Baleares]
    • Palma de Mallorca, Illes Balears [Islas Baleares], Spain, 07198
      • Hospital Son Llatzer ( Site 1105)
• United Kingdom
  • Leeds, United Kingdom, LS9 7TF
    • Leeds Teaching Hospitals NHS Trust ( Site 1209)
  • Rom Valley, United Kingdom, RM7 0AG
    • Queen's Hospital ( Site 1201)
  • Hampshire
    • Southampton, Hampshire, United Kingdom, SO16 6YD
      • Southampton General Hospital ( Site 1204)
  • London, City Of
    • London, London, City Of, United Kingdom, NW3 2QG
      • Royal Free NHS Foundation Trust ( Site 1200)
    • London, London, City Of, United Kingdom, W6 8RF
      • Charing Cross Hospital ( Site 1208)
  • Somerset
    • Taunton, Somerset, United Kingdom, TA1 5DA
      • Beacon Centre ( Site 1203)
• United States
  • California
    • Santa Rosa, California, United States, 95403
      • St Joseph Heritage Healthcare ( Site 1403)
  • Illinois
    • Evanston, Illinois, United States, 60201
      • North Shore University Health System ( Site 1413)
  • Indiana
    • Fort Wayne, Indiana, United States, 46845
      • Parkview Cancer Institute ( Site 1415)
  • Massachusetts
    • Worcester, Massachusetts, United States, 01655
      • UMass Memorial Medical Center ( Site 1417)
  • Michigan
    • Detroit, Michigan, United States, 48202
      • Henry Ford Hospital ( Site 1418)
  • Nebraska
    • Grand Island, Nebraska, United States, 68803
      • St. Francis Cancer Treatment Center ( Site 1421)
  • New Jersey
    • New Brunswick, New Jersey, United States, 08903
      • Rutgers Cancer Institute of New Jersey ( Site 1422)
  • Oklahoma
    • Tulsa, Oklahoma, United States, 74133
      • CTCA Southwestern ( Site 1428)
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19111
      • Fox Chase Cancer Center ( Site 1433)
  • South Dakota
    • Sioux Falls, South Dakota, United States, 57104
      • Sanford Cancer Center Oncology Clinic ( Site 1434)

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Male/female participants, who are at least 18 years of age on the day of signing informed consent with previously untreated, unresectable, pathologically confirmed NSCLC and Stage IIIA, IIIB or IIIC NSCLC by American Joint Committee on Cancer Version 8.
• No evidence of metastatic disease by whole body positron emission tomography/computed tomography (PET/ CT) scan, diagnostic quality CT scan, and brain imaging.
• Have measurable disease per RECIST 1.1 as assessed by the local site investigator/radiology.
• Have provided tumor tissue sample (core, incisional, or excisional biopsy).
• Have an Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1.
• Have adequate pulmonary function test (PFT)
• Have adequate organ function
• A male participant must agree to use contraception through the end of treatment and refrain from donating sperm during this period.
• A female participant is eligible to participate if she is not pregnant, not breastfeeding, and if participant is a woman of childbearing potential (WOCBP), agrees to follow the contraceptive guidance as provided in the protocol through the end of treatment.

Exclusion Criteria:

• A WOCBP who has a positive urine pregnancy test within 72 hours prior to treatment allocation
• Has small cell lung cancer.
• Has had documented weight loss >10% in the preceding 3 months.
• Participants whose radiation treatment plans are likely to encompass a volume of whole lung receiving >20 Gy in total (V20) of more than 31% of lung volume.
• Has received prior radiotherapy to the thorax, including radiotherapy to the esophagus or for breast cancer.
• Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent (programmed cell death protein 1 [PD-1] and its ligands, programmed cell death ligand 1 (PD-L1) and programmed cell death ligand 2 [PD-L2]) or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (eg, CTLA-4, OX-40, CD137).
• Has received a live vaccine within 30 days prior to the first dose of study drug.
• Has had an allogenic tissue/solid organ transplant.
• 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 treatment.
• Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg prednisone daily or equivalent) or any other form of immunosuppressive therapy within 7 days prior the first dose of study drug.
• Has a known additional malignancy that is progressing or has required active treatment within the past 5 years.
• Has severe hypersensitivity (Grade 3 or higher) to pembrolizumab and/or any of its excipients.
• Has a known severe hypersensitivity (Grade 3 or higher) 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 (ie, with use of disease modifying agents, corticosteroids or immunosuppressive drugs).
• 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 a known history of human immunodeficiency virus (HIV) infection. HIV testing is not required unless mandated by local health authority.
• Has a known history of hepatitis B (defined as hepatitis B surface antigen [HBsAg] reactive) or known active hepatitis C virus (defined as HCV RNA [qualitative] is detected) infection.
• Has a known history of active tuberculosis (TB; Bacillus tuberculosis).
• Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the participant's participation for the full duration of the study, or is not in the best interest of the participant to participate, in the opinion of the treating investigator.
• Has a known psychiatric or substance abuse disorder that would interfere with cooperating with the requirements of the study.
• Is pregnant or breastfeeding or expecting to conceive or father children within the projected duration of the study through the end of treatment.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort A; Participants received 1 cycle of carboplatin area under the curve (AUC) 6 mg/mL/min with paclitaxel 200 mg/m^2 and pembrolizumab 200 mg on Day 1. Approximately 3 weeks later, participants received carboplatin AUC 2 mg/mL/min with paclitaxel 45 mg/ m^2 administered weekly for 6 weeks along with 2 cycles of pembrolizumab 200 mg administered every 3 weeks (Q3W) in conjunction with standard thoracic radiotherapy (TRT) (60 Gray [Gy] in 2 Gy fractions administered 5 days per week for 6 weeks). Participants then received 14 additional cycles of pembrolizumab 200 mg administered Q3W. 1 cycle=21 days.	Drug: Pembrolizumab 200 mg; Pembrolizumab 200 mg intravenous (IV) infusion on Days 1 of each 3-week cycle for up to 17 cycles; Other Names: MK-3475; Drug: Paclitaxel 45 mg/m^2; Paclitaxel 45 mg/m^2 IV infusion on Days 1, 8, 15 of each 3-week cycle for Cycles 2, and 3 during radiation therapy.; Drug: Carboplatin AUC6; Carboplatin AUC6 IV infusion on Day 1 of the 21-day cycle for Cycle 1.; Radiation: Thoracic Radiation Therapy (TRT); The target total dose of TRT will be 60 Gy in 30 daily fractions of 2 Gy, prescribed to the planning target volume.; Drug: Paclitaxel 200 mg/m^2; Paclitaxel 200 mg/m^2 IV infusion on Day 1 of the 21-day cycle of Cycle 1.; Drug: Carboplatin AUC2; Carboplatin AUC2 IV infusion on Day 1, 8, 15 for Cycles 2 and 3 during radiation therapy.
Experimental: Cohort B; Participants received 3 cycles of cisplatin 75 mg/m^2 with pemetrexed 500 mg/m^2 and pembrolizumab 200 mg on Day 1 of each cycle. Treatment was given in conjunction with standard TRT (60 Gy in 2 Gy fractions administered 5 days per week for 6 weeks) in cycles 2 and 3. Participants then received 14 additional cycles of pembrolizumab 200 mg administered Q3W. 1 cycle=21 days.	Drug: Pembrolizumab 200 mg; Pembrolizumab 200 mg intravenous (IV) infusion on Days 1 of each 3-week cycle for up to 17 cycles; Other Names: MK-3475; Radiation: Thoracic Radiation Therapy (TRT); The target total dose of TRT will be 60 Gy in 30 daily fractions of 2 Gy, prescribed to the planning target volume.; Drug: Cisplatin 75 mg/m^2; Cisplatin 75 mg/m^2 IV infusion on Day 1 of each 21-day cycle for Cycles 1, 2, 3.; Drug: Pemetrexed 500 mg/m^2; Pemetrexed 500 mg/m^2 IV infusion on Day 1 of each 21-day cycle for Cycles 1, 2, and 3.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants Who Developed Grade 3 or Higher Pneumonitis	Pneumonitis included the MedDRA preferred terms for radiation pneumonitis are acute interstitial pneumonitis, autoimmune lung disease, interstitial lung disease, pneumonitis, idiopathic pneumonia syndrome, organizing pneumonia, and immune-mediated pneumonitis. As per common terminology criteria for Adverse Events, version 4.0, pneumonitis was graded as follows: Grade (Gr) 1- asymptomatic, clinical or diagnostic observations only; intervention not indicated; Gr 2- symptomatic, medical intervention indicated, limiting instrumental activities of daily living (ADL); Gr 3- severe symptoms; limiting self-care activities of daily living (ADL), oxygen indicated; Gr 4- life-threatening respiratory compromise; urgent intervention indicated (e.g., tracheotomy or intubation); Gr 5- death.	Up to approximately 3 years
Overall Response Rate (ORR) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1)	ORR was defined as the percentage of participants who experienced a complete response (CR; disappearance of all target lesions) or a partial response (PR; at least a 30% decrease in the sum of diameters of target lesions) and was assessed using modified RECIST 1.1 by blinded independent central review (BICR).	Up to approximately 3 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants Who Discontinued From 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 a study intervention. The number of participants who discontinued treatment due to an AE was assessed.	Up to approximately 1 year
Progression Free Survival (PFS) Per Response Criteria in Solid Tumors Version 1.1 (RECIST 1.1)	PFS was defined as the time from the first dose of study treatment to the date of the first documentation of disease progression, as determined by BICR per RECIST 1.1 or death due to any cause (whichever occurred first). Disease progression was defined as at least 20 percent (%) increase (including an absolute increase of at least 5 millimeters [mm]) in the sum of diameter of target lesions, taking as reference the smallest sum, and/or unequivocal progression of existing non-target lesions, and/or appearance of 1 or more new lesions. PFS was estimated and analyzed using the product-limit (Kaplan-Meier) method for censored data.	Up to approximately 5 1/2 years
Overall Survival (OS)	OS is defined as the time from enrollment to death due to any cause. OS was estimated and analyzed using the product-limit (Kaplan-Meier) method for censored data.	Up to approximately 5 1/2 years
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 with at least one AE was assessed.	Up to approximately 1 1/2 years

Collaborators and Investigators

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

Publications and helpful links

General Publications

• Jabbour SK, Lee KH, Frost N, Breder V, Kowalski DM, Pollock T, Levchenko E, Reguart N, Martinez-Marti A, Houghton B, Paoli JB, Safina S, Park K, Komiya T, Sanford A, Boolell V, Liu H, Samkari A, Keller SM, Reck M. Pembrolizumab Plus Concurrent Chemoradiation Therapy in Patients With Unresectable, Locally Advanced, Stage III Non-Small Cell Lung Cancer: The Phase 2 KEYNOTE-799 Nonrandomized Trial. JAMA Oncol. 2021 Jun 4;7(9):1-9. doi: 10.1001/jamaoncol.2021.2301. Online ahead of print.

Helpful Links

• Merck Clinical Trials Information

Study record dates

Study Major Dates

• Study Start (Actual): October 19, 2018
• Primary Completion (Actual): October 18, 2021
• Study Completion (Actual): March 19, 2024

Study Registration Dates

• First Submitted: August 13, 2018
• First Submitted That Met QC Criteria: August 13, 2018
• First Posted (Actual): August 15, 2018

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: March 6, 2025
• Last Verified: March 1, 2025

More Information

Terms related to this study

• Keywords: Programmed Cell Death-1 (PD1, PD-1); Programmed Cell Death 1 Ligand 1 (PDL1, PD-L1); Programmed Cell Death 1 Ligand 2 (PDL2, PD-L2)
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Respiratory Tract Diseases; Lung Diseases; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Antineoplastic Agents, Immunological; Immune Checkpoint Inhibitors; Antineoplastic Agents; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Folic Acid Antagonists; Nucleic Acid Synthesis Inhibitors; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Phytogenic; Albumin-Bound Paclitaxel; Pemetrexed; Carboplatin; Pembrolizumab; Paclitaxel
• Other Study ID Numbers: 3475-799; MK-3475-799 (Other Identifier: MSD Protocol Number); 2018-000714-37 (EudraCT Number)

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