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

Non-small Cell Lung Cancer Clinical Trial

— KEYNOTE-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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03631784
• Other study ID #: 3475-799
• Secondary ID: MK-3475-7992018-
• Status: Completed
• Phase: Phase 2
• Start date: October 19, 2018
• Est. completion date: March 19, 2024

Study information

• Verified date: March 2024
• Source: Merck Sharp & Dohme LLC
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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 objective response rate (ORR) by blinded independent central review (BICR).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 217
• Est. completion date: March 19, 2024
• Est. primary completion date: October 18, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Carcinoma, Non-Small-Cell Lung
• Lung Neoplasms
• Non-small Cell Lung Cancer

Intervention

Drug:
• Pembrolizumab 200 mg
Pembrolizumab 200 mg intravenous (IV) infusion on Days 1 of each 3-week cycle for up to 17 cycles
• 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.
• Carboplatin AUC6
Carboplatin AUC6 IV infusion on Day 1 of the 21-day cycle for Cycle 1.
• 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.
• 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.

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

Locations

Country	Name	City	State
Australia	Ballarat Health Services ( Site 0206)	Ballarat	Victoria
Australia	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
France	Clinique de L'Europe ( Site 0308)	Amiens	Somme
France	ICO Centre Paul Papin ( Site 0309)	Angers	Maine-et-Loire
France	CHU Jean Minjoz ( Site 0301)	Besancon	Doubs
France	Centre Jean Perrin ( Site 0304)	Clermont Ferrand	Puy-de-Dome
France	Clinique Clairval ( Site 0311)	Marseille	Bouches-du-Rhone
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	C.H. de Saint Quentin ( Site 0306)	Saint Quentin	Aisne
France	Institut de Cancerologie Gustave Roussy ( Site 0305)	Villejuif	Val-de-Marne
Germany	Charite Universitaetsmedizin Berlin - Campus-Virchow-Klinikum ( Site 0414)	Berlin
Germany	Augusta-Kranken-Anstalt Bochum ( Site 0401)	Bochum	Nordrhein-Westfalen
Germany	Klinikum Chemnitz gGmbH ( Site 0410)	Chemnitz	Sachsen
Germany	LungenClinic Grosshansdorf GmbH ( Site 0408)	Grosshansdorf	Schleswig-Holstein
Germany	Katholisches Marienkrankenhaus gGmbH ( Site 0411)	Hamburg
Germany	Thoraxklinik Heidelberg gGmbH am Universitaetsklinikum Heidelberg ( Site 0404)	Heidelberg	Baden-Wurttemberg
Germany	Universitatsklinikum Mannheim GmbH ( Site 0413)	Mannheim	Baden-Wurttemberg
Germany	Bethanien Krankenhaus Moers ( Site 0406)	Moers	Nordrhein-Westfalen
Korea, Republic of	Chungbuk National University Hospital ( Site 1003)	Cheongju si	Chungcheongbuk-do [Chungbuk]
Korea, Republic of	National Cancer Center ( Site 1002)	Goyang-si	Kyonggi-do
Korea, Republic of	Samsung Medical Center ( Site 1001)	Seoul	Seoul-teukbyeolsi [Seoul]
Korea, Republic of	Ulsan University Hospital ( Site 1000)	Ulsan	Ulsan-Kwangyokshi
New Zealand	Auckland City Hospital ( Site 0700)	Auckland
Poland	Centrum Onkologii im. Prof. Franciszka Lukaszczyka ( Site 0811)	Bydgoszcz	Kujawsko-pomorskie
Poland	Szpital Morski im. PCK. Szpitale Pomorskie Sp. Z o.o ( Site 0812)	Gdynia	Pomorskie
Poland	Szpital Wojewodzki w Koszalinie im. Mikolaja Kopernika ( Site 0813)	Koszalin	Zachodniopomorskie
Poland	Osrodek Badan Klinicznych przy Szpitalu Specjalistycznym ( Site 0802)	Krakow	Malopolskie
Poland	Narodowy Instytut Onkologii im. Marii Sklodowskiej-Curie ( Site 0800)	Warszawa	Mazowieckie
Russian Federation	Republican Clinical Oncology Dispensary of Tatarstan MoH ( Site 0910)	Kazan	Tatarstan, Respublika
Russian Federation	Blokhin National Medical Oncology ( Site 0902)	Moscow	Moskva
Russian Federation	National Medical Research Center of Oncology N.A. N.N. Petrov ( Site 0904)	St. Petersburg	Sankt-Peterburg
Russian Federation	Republican Clinical Oncology Dispensary of Republic of Bashkortostan ( Site 0903)	Ufa	Baskortostan, Respublika
Spain	Hospital Clinic de Barcelona ( Site 1100)	Barcelona	Barcelona [Barcelona]
Spain	Hospital Universitari Vall d Hebron ( Site 1101)	Barcelona	Barcelona [Barcelona]
Spain	Clinica Universitaria de Navarra ( Site 1102)	Madrid
Spain	Hospital Son Llatzer ( Site 1105)	Palma de Mallorca	Illes Balears [Islas Baleares]
Spain	Hospital Universitario Virgen Macarena ( Site 1103)	Sevilla
United Kingdom	Leeds Teaching Hospitals NHS Trust ( Site 1209)	Leeds
United Kingdom	Charing Cross Hospital ( Site 1208)	London	London, City Of
United Kingdom	Royal Free NHS Foundation Trust ( Site 1200)	London	London, City Of
United Kingdom	Queen's Hospital ( Site 1201)	Rom Valley
United Kingdom	Southampton General Hospital ( Site 1204)	Southampton	Hampshire
United Kingdom	Beacon Centre ( Site 1203)	Taunton	Somerset
United States	Henry Ford Hospital ( Site 1418)	Detroit	Michigan
United States	North Shore University Health System ( Site 1413)	Evanston	Illinois
United States	Parkview Cancer Institute ( Site 1415)	Fort Wayne	Indiana
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	Fox Chase Cancer Center ( Site 1433)	Philadelphia	Pennsylvania
United States	St Joseph Heritage Healthcare ( Site 1403)	Santa Rosa	California
United States	Sanford Cancer Center Oncology Clinic ( Site 1434)	Sioux Falls	South Dakota
United States	CTCA Southwestern ( Site 1428)	Tulsa	Oklahoma
United States	UMass Memorial Medical Center ( Site 1417)	Worcester	Massachusetts

Sponsors (1)

Lead Sponsor	Collaborator
Merck Sharp & Dohme LLC

Countries where clinical trial is conducted

United States,  Australia,  France,  Germany,  Korea, Republic of,  New Zealand,  Poland,  Russian Federation,  Spain,  United Kingdom, 

References & 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 Chemoradiat — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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	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 years
Secondary	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 years
Secondary	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 1/4 years
Secondary	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

External Links

•   Merck Clinical Trials Information