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

About this trial
This is an interventional treatment trial for Non-small Cell Lung Cancer focused on measuring 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)
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.
Sites / Locations
- St Joseph Heritage Healthcare ( Site 1403)
- North Shore University Health System ( Site 1413)
- Parkview Cancer Institute ( Site 1415)
- UMass Memorial Medical Center ( Site 1417)
- Henry Ford Hospital ( Site 1418)
- St. Francis Cancer Treatment Center ( Site 1421)
- Rutgers Cancer Institute of New Jersey ( Site 1422)
- CTCA Southwestern ( Site 1428)
- Fox Chase Cancer Center ( Site 1433)
- Sanford Cancer Center Oncology Clinic ( Site 1434)
- Blacktown Hospital Western Sydney Local Health District ( Site 0204)
- MNCCI Port Macquarie Base Hospital ( Site 0200)
- Southern Medical Day Care Centre ( Site 0201)
- Ballarat Health Services ( Site 0206)
- C.H. de Saint Quentin ( Site 0306)
- Clinique Clairval ( Site 0311)
- CHU Jean Minjoz ( Site 0301)
- Institut du Cancer de Montpellier ( Site 0300)
- C.H.R.U. de Rennes. Hopital de Pontchaillou ( Site 0302)
- ICO Centre Paul Papin ( Site 0309)
- Centre Jean Perrin ( Site 0304)
- Clinique de L'Europe ( Site 0308)
- Institut de Cancerologie Gustave Roussy ( Site 0305)
- Thoraxklinik Heidelberg gGmbH am Universitaetsklinikum Heidelberg ( Site 0404)
- Universitatsklinikum Mannheim GmbH ( Site 0413)
- Augusta-Kranken-Anstalt Bochum ( Site 0401)
- Bethanien Krankenhaus Moers ( Site 0406)
- Klinikum Chemnitz gGmbH ( Site 0410)
- LungenClinic Grosshansdorf GmbH ( Site 0408)
- Charite Universitaetsmedizin Berlin - Campus-Virchow-Klinikum ( Site 0414)
- Katholisches Marienkrankenhaus gGmbH ( Site 0411)
- Chungbuk National University Hospital ( Site 1003)
- National Cancer Center ( Site 1002)
- Samsung Medical Center ( Site 1001)
- Ulsan University Hospital ( Site 1000)
- Auckland City Hospital ( Site 0700)
- Centrum Onkologii im. Prof. Franciszka Lukaszczyka ( Site 0811)
- Osrodek Badan Klinicznych przy Szpitalu Specjalistycznym ( Site 0802)
- Narodowy Instytut Onkologii im. Marii Sklodowskiej-Curie ( Site 0800)
- Szpital Morski im. PCK. Szpitale Pomorskie Sp. Z o.o ( Site 0812)
- Szpital Wojewodzki w Koszalinie im. Mikolaja Kopernika ( Site 0813)
- Republican Clinical Oncology Dispensary of Republic of Bashkortostan ( Site 0903)
- Blokhin National Medical Oncology ( Site 0902)
- National Medical Research Center of Oncology N.A. N.N. Petrov ( Site 0904)
- Republican Clinical Oncology Dispensary of Tatarstan MoH ( Site 0910)
- Hospital Universitari Vall d Hebron ( Site 1101)
- Hospital Clinic de Barcelona ( Site 1100)
- Hospital Son Llatzer ( Site 1105)
- Clinica Universitaria de Navarra ( Site 1102)
- Hospital Universitario Virgen Macarena ( Site 1103)
- Southampton General Hospital ( Site 1204)
- Royal Free NHS Foundation Trust ( Site 1200)
- Charing Cross Hospital ( Site 1208)
- Beacon Centre ( Site 1203)
- Leeds Teaching Hospitals NHS Trust ( Site 1209)
- Queen's Hospital ( Site 1201)
Arms of the Study
Arm 1
Arm 2
Experimental
Experimental
Cohort A
Cohort B
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.
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.