Clinical trial NCT03631784: A Trial of Pembrolizumab in Combination With Chemotherapy and Radiotherapy in Stage III NSCLC (KEYNOTE-799, MK-3475-799)
Official title: 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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
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)
Lead sponsor: Merck Sharp & Dohme LLC
Sponsor class: INDUSTRY
First posted: 2018-08-15
Enrollment: 216
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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).


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.

Primary outcomes:
measure: Percentage of Participants Who Developed Grade 3 or Higher Pneumonitis
timeFrame: Up to approximately 3 years
measure: Overall Response Rate (ORR) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1)
timeFrame: Up to approximately 3 years
Secondary outcomes:
measure: Progression Free Survival (PFS) Per Response Criteria in Solid Tumors Version 1.1 (RECIST 1.1)
timeFrame: Up to approximately 5 1/2 years
measure: Overall Survival (OS)
timeFrame: Up to approximately 5 1/2 years
measure: Number of Participants Who Experienced an Adverse Event (AE)
timeFrame: Up to approximately 1 1/2 years
measure: Number of Participants Who Discontinued From Study Treatment Due to an AE
timeFrame: Up to approximately 1 year
Other outcomes:
Locations:
city: Santa Rosa
country: United States
facility: St Joseph Heritage Healthcare ( Site 1403)
state: California
city: Evanston
country: United States
facility: North Shore University Health System ( Site 1413)
state: Illinois
city: Fort Wayne
country: United States
facility: Parkview Cancer Institute ( Site 1415)
state: Indiana
city: Worcester
country: United States
facility: UMass Memorial Medical Center ( Site 1417)
state: Massachusetts
city: Detroit
country: United States
facility: Henry Ford Hospital ( Site 1418)
state: Michigan
city: Grand Island
country: United States
facility: St. Francis Cancer Treatment Center ( Site 1421)
state: Nebraska
city: New Brunswick
country: United States
facility: Rutgers Cancer Institute of New Jersey ( Site 1422)
state: New Jersey
city: Tulsa
country: United States
facility: CTCA Southwestern ( Site 1428)
state: Oklahoma
city: Philadelphia
country: United States
facility: Fox Chase Cancer Center ( Site 1433)
state: Pennsylvania
city: Sioux Falls
country: United States
facility: Sanford Cancer Center Oncology Clinic ( Site 1434)
state: South Dakota
city: Blacktown
country: Australia
facility: Blacktown Hospital Western Sydney Local Health District ( Site 0204)
state: New South Wales
city: Port Macquarie
country: Australia
facility: MNCCI Port Macquarie Base Hospital ( Site 0200)
state: New South Wales
city: Wollongong
country: Australia
facility: Southern Medical Day Care Centre ( Site 0201)
state: New South Wales
city: Ballarat
country: Australia
facility: Ballarat Health Services ( Site 0206)
state: Victoria
city: Saint Quentin
country: France
facility: C.H. de Saint Quentin ( Site 0306)
state: Aisne
city: Marseille
country: France
facility: Clinique Clairval ( Site 0311)
state: Bouches-du-Rhone
city: Besancon
country: France
facility: CHU Jean Minjoz ( Site 0301)
state: Doubs
city: Montpellier
country: France
facility: Institut du Cancer de Montpellier ( Site 0300)
state: Herault
city: Rennes.
country: France
facility: C.H.R.U. de Rennes. Hopital de Pontchaillou ( Site 0302)
state: Ille-et-Vilaine
city: Angers
country: France
facility: ICO Centre Paul Papin ( Site 0309)
state: Maine-et-Loire
city: Clermont Ferrand
country: France
facility: Centre Jean Perrin ( Site 0304)
state: Puy-de-Dome
city: Amiens
country: France
facility: Clinique de L'Europe ( Site 0308)
state: Somme
city: Villejuif
country: France
facility: Institut de Cancerologie Gustave Roussy ( Site 0305)
state: Val-de-Marne
city: Heidelberg
country: Germany
facility: Thoraxklinik Heidelberg gGmbH am Universitaetsklinikum Heidelberg ( Site 0404)
state: Baden-Wurttemberg
city: Mannheim
country: Germany
facility: Universitatsklinikum Mannheim GmbH ( Site 0413)
state: Baden-Wurttemberg
city: Bochum
country: Germany
facility: Augusta-Kranken-Anstalt Bochum ( Site 0401)
state: Nordrhein-Westfalen
city: Moers
country: Germany
facility: Bethanien Krankenhaus Moers ( Site 0406)
state: Nordrhein-Westfalen
city: Chemnitz
country: Germany
facility: Klinikum Chemnitz gGmbH ( Site 0410)
state: Sachsen
city: Grosshansdorf
country: Germany
facility: LungenClinic Grosshansdorf GmbH ( Site 0408)
state: Schleswig-Holstein
city: Berlin
country: Germany
facility: Charite Universitaetsmedizin Berlin - Campus-Virchow-Klinikum ( Site 0414)
city: Hamburg
country: Germany
facility: Katholisches Marienkrankenhaus gGmbH ( Site 0411)
city: Cheongju si
country: Korea, Republic of
facility: Chungbuk National University Hospital ( Site 1003)
state: Chungcheongbuk-do [Chungbuk]
city: Goyang-si
country: Korea, Republic of
facility: National Cancer Center ( Site 1002)
state: Kyonggi-do
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center ( Site 1001)
state: Seoul-teukbyeolsi [Seoul]
city: Ulsan
country: Korea, Republic of
facility: Ulsan University Hospital ( Site 1000)
state: Ulsan-Kwangyokshi
city: Auckland
country: New Zealand
facility: Auckland City Hospital ( Site 0700)
city: Bydgoszcz
country: Poland
facility: Centrum Onkologii im. Prof. Franciszka Lukaszczyka ( Site 0811)
state: Kujawsko-pomorskie
city: Krakow
country: Poland
facility: Osrodek Badan Klinicznych przy Szpitalu Specjalistycznym ( Site 0802)
state: Malopolskie
city: Warszawa
country: Poland
facility: Narodowy Instytut Onkologii im. Marii Sklodowskiej-Curie ( Site 0800)
state: Mazowieckie
city: Gdynia
country: Poland
facility: Szpital Morski im. PCK. Szpitale Pomorskie Sp. Z o.o ( Site 0812)
state: Pomorskie
city: Koszalin
country: Poland
facility: Szpital Wojewodzki w Koszalinie im. Mikolaja Kopernika ( Site 0813)
state: Zachodniopomorskie
city: Ufa
country: Russian Federation
facility: Republican Clinical Oncology Dispensary of Republic of Bashkortostan ( Site 0903)
state: Baskortostan, Respublika
city: Moscow
country: Russian Federation
facility: Blokhin National Medical Oncology ( Site 0902)
state: Moskva
city: St. Petersburg
country: Russian Federation
facility: National Medical Research Center of Oncology N.A. N.N. Petrov ( Site 0904)
state: Sankt-Peterburg
city: Kazan
country: Russian Federation
facility: Republican Clinical Oncology Dispensary of Tatarstan MoH ( Site 0910)
state: Tatarstan, Respublika
city: Barcelona
country: Spain
facility: Hospital Universitari Vall d Hebron ( Site 1101)
state: Barcelona [Barcelona]
city: Barcelona
country: Spain
facility: Hospital Clinic de Barcelona ( Site 1100)
state: Barcelona [Barcelona]
city: Palma de Mallorca
country: Spain
facility: Hospital Son Llatzer ( Site 1105)
state: Illes Balears [Islas Baleares]
city: Madrid
country: Spain
facility: Clinica Universitaria de Navarra ( Site 1102)
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen Macarena ( Site 1103)
city: Southampton
country: United Kingdom
facility: Southampton General Hospital ( Site 1204)
state: Hampshire
city: London
country: United Kingdom
facility: Royal Free NHS Foundation Trust ( Site 1200)
state: London, City Of
city: London
country: United Kingdom
facility: Charing Cross Hospital ( Site 1208)
state: London, City Of
city: Taunton
country: United Kingdom
facility: Beacon Centre ( Site 1203)
state: Somerset
city: Leeds
country: United Kingdom
facility: Leeds Teaching Hospitals NHS Trust ( Site 1209)
city: Rom Valley
country: United Kingdom
facility: Queen's Hospital ( Site 1201)
Study officials:
affiliation: Merck Sharp & Dohme LLC
name: Medical Director
role: STUDY_DIRECTOR
References:
citation: 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.