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

NCT ID: NCT03631784

Last Updated: 2025-03-25

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 216 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-10-19
• Study Completion Date: 2024-03-19

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

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.

Group Type: EXPERIMENTAL

Pembrolizumab 200 mg

Intervention Type: DRUG

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

Paclitaxel 45 mg/m^2

Intervention Type: 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.

Carboplatin AUC6

Intervention Type: DRUG

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

Thoracic Radiation Therapy (TRT)

Intervention Type: RADIATION

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

Paclitaxel 200 mg/m^2

Intervention Type: DRUG

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

Carboplatin AUC2

Intervention Type: DRUG

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

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.

Group Type: EXPERIMENTAL

Pembrolizumab 200 mg

Intervention Type: DRUG

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

Cisplatin 75 mg/m^2

Intervention Type: DRUG

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

Pemetrexed 500 mg/m^2

Intervention Type: DRUG

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

Thoracic Radiation Therapy (TRT)

Intervention Type: RADIATION

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

Interventions

Pembrolizumab 200 mg

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

Intervention Type: 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.

Intervention Type: DRUG

Carboplatin AUC6

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

Intervention Type: 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.

Intervention Type: 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.

Intervention Type: DRUG

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.

Intervention Type: RADIATION

Paclitaxel 200 mg/m^2

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

Intervention Type: DRUG

Carboplatin AUC2

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

Intervention Type: DRUG

Other Intervention Names

MK-3475

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Merck Sharp & Dohme LLC

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Medical Director

Role: STUDY_DIRECTOR

Merck Sharp & Dohme LLC

Locations

St Joseph Heritage Healthcare ( Site 1403)

Santa Rosa, California, United States

North Shore University Health System ( Site 1413)

Evanston, Illinois, United States

Parkview Cancer Institute ( Site 1415)

Fort Wayne, Indiana, United States

UMass Memorial Medical Center ( Site 1417)

Worcester, Massachusetts, United States

Henry Ford Hospital ( Site 1418)

Detroit, Michigan, United States

St. Francis Cancer Treatment Center ( Site 1421)

Grand Island, Nebraska, United States

Rutgers Cancer Institute of New Jersey ( Site 1422)

New Brunswick, New Jersey, United States

CTCA Southwestern ( Site 1428)

Tulsa, Oklahoma, United States

Fox Chase Cancer Center ( Site 1433)

Philadelphia, Pennsylvania, United States

Sanford Cancer Center Oncology Clinic ( Site 1434)

Sioux Falls, South Dakota, United States

Blacktown Hospital Western Sydney Local Health District ( Site 0204)

Blacktown, New South Wales, Australia

MNCCI Port Macquarie Base Hospital ( Site 0200)

Port Macquarie, New South Wales, Australia

Southern Medical Day Care Centre ( Site 0201)

Wollongong, New South Wales, Australia

Ballarat Health Services ( Site 0206)

Ballarat, Victoria, Australia

C.H. de Saint Quentin ( Site 0306)

Saint-Quentin, Aisne, France

Clinique Clairval ( Site 0311)

Marseille, Bouches-du-Rhone, France

CHU Jean Minjoz ( Site 0301)

Besançon, Doubs, France

Institut du Cancer de Montpellier ( Site 0300)

Montpellier, Herault, France

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

Rennes, Ille-et-Vilaine, France

ICO Centre Paul Papin ( Site 0309)

Angers, Maine-et-Loire, France

Centre Jean Perrin ( Site 0304)

Clermont-Ferrand, Puy-de-Dome, France

Clinique de L'Europe ( Site 0308)

Amiens, Somme, France

Institut de Cancerologie Gustave Roussy ( Site 0305)

Villejuif, Val-de-Marne, France

Thoraxklinik Heidelberg gGmbH am Universitaetsklinikum Heidelberg ( Site 0404)

Heidelberg, Baden-Wurttemberg, Germany

Universitatsklinikum Mannheim GmbH ( Site 0413)

Mannheim, Baden-Wurttemberg, Germany

Augusta-Kranken-Anstalt Bochum ( Site 0401)

Bochum, North Rhine-Westphalia, Germany

Bethanien Krankenhaus Moers ( Site 0406)

Moers, North Rhine-Westphalia, Germany

Klinikum Chemnitz gGmbH ( Site 0410)

Chemnitz, Saxony, Germany

LungenClinic Grosshansdorf GmbH ( Site 0408)

Großhansdorf, Schleswig-Holstein, Germany

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

Berlin, , Germany

Katholisches Marienkrankenhaus gGmbH ( Site 0411)

Hamburg, , Germany

Auckland City Hospital ( Site 0700)

Auckland, , New Zealand

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

Bydgoszcz, Kuyavian-Pomeranian Voivodeship, Poland

Osrodek Badan Klinicznych przy Szpitalu Specjalistycznym ( Site 0802)

Krakow, Lesser Poland Voivodeship, Poland

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

Warsaw, Masovian Voivodeship, Poland

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

Gdynia, Pomeranian Voivodeship, Poland

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

Koszalin, West Pomeranian Voivodeship, Poland

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

Ufa, Baskortostan, Respublika, Russia

Blokhin National Medical Oncology ( Site 0902)

Moscow, Moscow, Russia

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

Saint Petersburg, Sankt-Peterburg, Russia

Republican Clinical Oncology Dispensary of Tatarstan MoH ( Site 0910)

Kazan', Tatarstan, Respublika, Russia

Chungbuk National University Hospital ( Site 1003)

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

National Cancer Center ( Site 1002)

Goyang-si, Kyonggi-do, South Korea

Samsung Medical Center ( Site 1001)

Seoul, Seoul-teukbyeolsi [Seoul], South Korea

Ulsan University Hospital ( Site 1000)

Ulsan, Ulsan-Kwangyokshi, South Korea

Hospital Universitari Vall d Hebron ( Site 1101)

Barcelona, Barcelona [Barcelona], Spain

Hospital Clinic de Barcelona ( Site 1100)

Barcelona, Barcelona [Barcelona], Spain

Hospital Son Llatzer ( Site 1105)

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

Clinica Universitaria de Navarra ( Site 1102)

Madrid, , Spain

Hospital Universitario Virgen Macarena ( Site 1103)

Seville, , Spain

Southampton General Hospital ( Site 1204)

Southampton, Hampshire, United Kingdom

Royal Free NHS Foundation Trust ( Site 1200)

London, London, City of, United Kingdom

Charing Cross Hospital ( Site 1208)

London, London, City of, United Kingdom

Beacon Centre ( Site 1203)

Taunton, Somerset, United Kingdom

Queen's Hospital ( Site 1201)

Rom Valley, United Kingdom, United Kingdom

Leeds Teaching Hospitals NHS Trust ( Site 1209)

Leeds, , United Kingdom

Countries

United States; Australia; France; Germany; New Zealand; Poland; Russia; South Korea; Spain; United Kingdom

References

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.

Reference Type: RESULT

PMID: 34086039 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Related Links

https://www.merckclinicaltrials.com

Merck Clinical Trials Information

Other Identifiers

MK-3475-799

Identifier Type: OTHER

Identifier Source: secondary_id

2018-000714-37

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

3475-799

Identifier Type: -

Identifier Source: org_study_id