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

NCT03631784 | Completed Phase 2 Results DMC FDA Drug

• 3 other identifiers: 3475-799MK-3475-7992018-000714-37
• Study Type: interventional
• Target: 216
• Locations: 10 countries
• Sites: 56

Brief Summary

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).

Conditions

Non-small Cell Lung Cancer

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)

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (4)

• Progression Free Survival (PFS) Per Response Criteria in Solid Tumors Version 1.1 (RECIST 1.1)

  Up to approximately 5 1/2 years

• Overall Survival (OS)

  Up to approximately 5 1/2 years

• Number of Participants Who Experienced an Adverse Event (AE)

  Up to approximately 1 1/2 years

• Number of Participants Who Discontinued From Study Treatment Due to an AE

  Up to approximately 1 year

Study Arms (2)

Cohort A

EXPERIMENTAL

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; Drug: Paclitaxel 45 mg/m^2; Drug: Carboplatin AUC6; Radiation: Thoracic Radiation Therapy (TRT); Drug: Paclitaxel 200 mg/m^2; Drug: Carboplatin AUC2

Cohort B

EXPERIMENTAL

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; Drug: Cisplatin 75 mg/m^2; Drug: Pemetrexed 500 mg/m^2; Radiation: Thoracic Radiation Therapy (TRT)

Interventions

Pembrolizumab 200 mg DRUG

Pembrolizumab 200 mg intravenous (IV) infusion on Days 1 of each 3-week cycle for up to 17 cycles

Also known as: MK-3475

Cohort A; Cohort B

Paclitaxel 45 mg/m^2 DRUG

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.

Cohort A

Carboplatin AUC6 DRUG

Carboplatin AUC6 IV infusion on Day 1 of the 21-day cycle for Cycle 1.

Cohort A

Cisplatin 75 mg/m^2 DRUG

Cisplatin 75 mg/m\^2 IV infusion on Day 1 of each 21-day cycle for Cycles 1, 2, 3.

Cohort B

Pemetrexed 500 mg/m^2 DRUG

Pemetrexed 500 mg/m\^2 IV infusion on Day 1 of each 21-day cycle for Cycles 1, 2, and 3.

Cohort B

Thoracic Radiation Therapy (TRT) RADIATION

The target total dose of TRT will be 60 Gy in 30 daily fractions of 2 Gy, prescribed to the planning target volume.

Cohort A; Cohort B

Paclitaxel 200 mg/m^2 DRUG

Paclitaxel 200 mg/m\^2 IV infusion on Day 1 of the 21-day cycle of Cycle 1.

Cohort A

Carboplatin AUC2 DRUG

Carboplatin AUC2 IV infusion on Day 1, 8, 15 for Cycles 2 and 3 during radiation therapy.

Cohort A

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Merck Sharp & Dohme LLC: lead

Study Sites (56)

St Joseph Heritage Healthcare ( Site 1403)

Santa Rosa, California, 95403, United States

Location

North Shore University Health System ( Site 1413)

Evanston, Illinois, 60201, United States

Location

Parkview Cancer Institute ( Site 1415)

Fort Wayne, Indiana, 46845, United States

Location

UMass Memorial Medical Center ( Site 1417)

Worcester, Massachusetts, 01655, United States

Location

Henry Ford Hospital ( Site 1418)

Detroit, Michigan, 48202, United States

Location

St. Francis Cancer Treatment Center ( Site 1421)

Grand Island, Nebraska, 68803, United States

Location

Rutgers Cancer Institute of New Jersey ( Site 1422)

New Brunswick, New Jersey, 08903, United States

Location

CTCA Southwestern ( Site 1428)

Tulsa, Oklahoma, 74133, United States

Location

Fox Chase Cancer Center ( Site 1433)

Philadelphia, Pennsylvania, 19111, United States

Location

Sanford Cancer Center Oncology Clinic ( Site 1434)

Sioux Falls, South Dakota, 57104, United States

Location

Blacktown Hospital Western Sydney Local Health District ( Site 0204)

Blacktown, New South Wales, 2148, Australia

Location

MNCCI Port Macquarie Base Hospital ( Site 0200)

Port Macquarie, New South Wales, 2444, Australia

Location

Southern Medical Day Care Centre ( Site 0201)

Wollongong, New South Wales, 2500, Australia

Location

Ballarat Health Services ( Site 0206)

Ballarat, Victoria, 3350, Australia

Location

C.H. de Saint Quentin ( Site 0306)

Saint-Quentin, Aisne, 02321, France

Location

Clinique Clairval ( Site 0311)

Marseille, Bouches-du-Rhone, 13009, France

Location

CHU Jean Minjoz ( Site 0301)

Besançon, Doubs, 25000, France

Location

Institut du Cancer de Montpellier ( Site 0300)

Montpellier, Herault, 34298, France

Location

C.H.R.U. de Rennes. Hopital de Pontchaillou ( Site 0302)

Rennes, Ille-et-Vilaine, 35033, France

Location

ICO Centre Paul Papin ( Site 0309)

Angers, Maine-et-Loire, 49055, France

Location

Centre Jean Perrin ( Site 0304)

Clermont-Ferrand, Puy-de-Dome, 63011, France

Location

Clinique de L'Europe ( Site 0308)

Amiens, Somme, 80000, France

Location

Institut de Cancerologie Gustave Roussy ( Site 0305)

Villejuif, Val-de-Marne, 94800, France

Location

Thoraxklinik Heidelberg gGmbH am Universitaetsklinikum Heidelberg ( Site 0404)

Heidelberg, Baden-Wurttemberg, 69126, Germany

Location

Universitatsklinikum Mannheim GmbH ( Site 0413)

Mannheim, Baden-Wurttemberg, 68167, Germany

Location

Augusta-Kranken-Anstalt Bochum ( Site 0401)

Bochum, North Rhine-Westphalia, 44791, Germany

Location

Bethanien Krankenhaus Moers ( Site 0406)

Moers, North Rhine-Westphalia, 47441, Germany

Location

Klinikum Chemnitz gGmbH ( Site 0410)

Chemnitz, Saxony, 09113, Germany

Location

LungenClinic Grosshansdorf GmbH ( Site 0408)

Großhansdorf, Schleswig-Holstein, 22927, Germany

Location

Charite Universitaetsmedizin Berlin - Campus-Virchow-Klinikum ( Site 0414)

Berlin, 13353, Germany

Location

Katholisches Marienkrankenhaus gGmbH ( Site 0411)

Hamburg, 22087, Germany

Location

Auckland City Hospital ( Site 0700)

Auckland, 1023, New Zealand

Location

Centrum Onkologii im. Prof. Franciszka Lukaszczyka ( Site 0811)

Bydgoszcz, Kuyavian-Pomeranian Voivodeship, 85-796, Poland

Location

Osrodek Badan Klinicznych przy Szpitalu Specjalistycznym ( Site 0802)

Krakow, Lesser Poland Voivodeship, 31-826, Poland

Location

Narodowy Instytut Onkologii im. Marii Sklodowskiej-Curie ( Site 0800)

Warsaw, Masovian Voivodeship, 02-781, Poland

Location

Szpital Morski im. PCK. Szpitale Pomorskie Sp. Z o.o ( Site 0812)

Gdynia, Pomeranian Voivodeship, 81-519, Poland

Location

Szpital Wojewodzki w Koszalinie im. Mikolaja Kopernika ( Site 0813)

Koszalin, West Pomeranian Voivodeship, 75-581, Poland

Location

Republican Clinical Oncology Dispensary of Republic of Bashkortostan ( Site 0903)

Ufa, Baskortostan, Respublika, 450054, Russia

Location

Blokhin National Medical Oncology ( Site 0902)

Moscow, Moscow, 115478, Russia

Location

National Medical Research Center of Oncology N.A. N.N. Petrov ( Site 0904)

Saint Petersburg, Sankt-Peterburg, 197758, Russia

Location

Republican Clinical Oncology Dispensary of Tatarstan MoH ( Site 0910)

Kazan', Tatarstan, Respublika, 420029, Russia

Location

Chungbuk National University Hospital ( Site 1003)

Cheongju-si, Chungcheongbuk-do [Chungbuk], 28644, South Korea

Location

National Cancer Center ( Site 1002)

Goyang-si, Kyonggi-do, 10408, South Korea

Location

Samsung Medical Center ( Site 1001)

Seoul, Seoul-teukbyeolsi [Seoul], 06351, South Korea

Location

Ulsan University Hospital ( Site 1000)

Ulsan, Ulsan-Kwangyokshi, 44033, South Korea

Location

Hospital Universitari Vall d Hebron ( Site 1101)

Barcelona, Barcelona [Barcelona], 08035, Spain

Location

Hospital Clinic de Barcelona ( Site 1100)

Barcelona, Barcelona [Barcelona], 08036, Spain

Location

Hospital Son Llatzer ( Site 1105)

Palma de Mallorca, Illes Balears [Islas Baleares], 07198, Spain

Location

Clinica Universitaria de Navarra ( Site 1102)

Madrid, 28027, Spain

Location

Hospital Universitario Virgen Macarena ( Site 1103)

Seville, 41009, Spain

Location

Southampton General Hospital ( Site 1204)

Southampton, Hampshire, SO16 6YD, United Kingdom

Location

Royal Free NHS Foundation Trust ( Site 1200)

London, London, City of, NW3 2QG, United Kingdom

Location

Charing Cross Hospital ( Site 1208)

London, London, City of, W6 8RF, United Kingdom

Location

Beacon Centre ( Site 1203)

Taunton, Somerset, TA1 5DA, United Kingdom

Location

Queen's Hospital ( Site 1201)

Rom Valley, United Kingdom, RM7 0AG, United Kingdom

Location

Leeds Teaching Hospitals NHS Trust ( Site 1209)

Leeds, LS9 7TF, United Kingdom

Location

Related Publications (1)

• 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.

  PMID: 34086039 RESULT

Related Links

• Merck Clinical Trials Information

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung; Parkinson Disease 4, Autosomal Dominant Lewy Body

Interventions

pembrolizumab; Paclitaxel; Cisplatin; Pemetrexed

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Guanine; Hypoxanthines; Purinones; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Glutamates; Amino Acids, Acidic; Amino Acids; Amino Acids, Peptides, and Proteins; Amino Acids, Dicarboxylic

Results Point of Contact

• Title: Senior Vice President, Global Clinical Development
• Organization: Merck Sharp & Dohme LLC

ClinicalTrialsDisclosure@msd.com

1-800-672-6372

Study Officials

• Medical Director

  Merck Sharp & Dohme LLC

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 13, 2018
• First Posted: August 15, 2018
• Study Start: October 19, 2018
• Primary Completion: October 18, 2021
• Study Completion: March 19, 2024
• Last Updated: March 25, 2025
• Results First Posted: November 2, 2022

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will share

Locations

AU (4); FR (9); NZ (1); PL (5); RU (4); KR (4); US (10); ES (5); GB (6); DE (8)