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).
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
DOUBLE
Enrollment
216
Pembrolizumab 200 mg intravenous (IV) infusion on Days 1 of each 3-week cycle for up to 17 cycles
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 IV infusion on Day 1 of the 21-day cycle for Cycle 1.
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 IV infusion on Day 1 of each 21-day cycle for Cycles 1, 2, and 3.
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 IV infusion on Day 1 of the 21-day cycle of Cycle 1.
Carboplatin AUC2 IV infusion on Day 1, 8, 15 for Cycles 2 and 3 during radiation therapy.
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
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.
Time frame: 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).
Time frame: Up to approximately 3 years
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.
Time frame: Up to approximately 5 1/2 years
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.
Time frame: Up to approximately 5 1/2 years
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.
Time frame: Up to approximately 1 1/2 years
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.
Time frame: Up to approximately 1 year
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.
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
...and 46 more locations