NSCLC comprises of approximately 84 percent (%) of all lung cancers and is often diagnosed at advanced stage due to poor prognosis. Dostarlimab is an immunoglobulin G (IgG)4 kappa humanized monoclonal antibody (mAb) that binds with high affinity to programmed cell death protein 1 (PD 1), resulting in inhibition of binding to programmed death ligand 1 (PD L1) and programmed death ligand 2 (PD L2). This study aims to compare the efficacy and safety PD-1 inhibitors dostarlimab and pembrolizumab, when administered in combination with chemotherapy (pemetrexed, cisplatin and carboplatin), in participants with non-squamous NSCLC without a known sensitizing epidermal growth factor receptor (EGFR), anaplastic lymphoma kinase (ALK), or receptor tyrosine kinase-1 (ROS-1) mutation, BRAF V600E mutation, or other genomic aberration for which an approved targeted therapy is available. A total of approximately 240 participants will be enrolled in the study for a period of 5 years.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
DOUBLE
Enrollment
243
Dostarlimab will be administered through a 30 minute infusion at a dose of 500 milligrams (mg) intravenously (IV) every 3 weeks (Q3W) up to a maximum of 35 cycles (each cycle of 21 days).
Pembrolizumab will be administered through a 30 minute infusion at a dose of 200 mg Q3W up to a maximum of 35 cycles (each cycle of 21 days).
Pemetrexed will be administered at 500 milligram per meter square (mg/m\^2 ) IV through a 10 minute IV infusion Q3W, up to a maximum of 35 cycles (each cycle of 21 days). Cisplatin will be administered at 75 mg/m\^2 through a 30 minute IV infusion Q3W for 4 cycles (each cycle of 21 days) as per investigator decision. Carboplatin will also be administered at area under the concentration time curve 5 milligram/milliliters/minute (mg/mL/min) (maximum dose: 750 mg) through a 15 to 60 minute IV infusion Q3W for 4 cycles (each cycle of 21 days) as per investigator decision.
GSK Investigational Site
Denver, North Carolina, United States
GSK Investigational Site
Cincinnati, Ohio, United States
GSK Investigational Site
Fairfax, Virginia, United States
GSK Investigational Site
Buenos Aires, Argentina
GSK Investigational Site
Ciudad Autonoma de Buenos Aire, Argentina
Objective Response Rate (ORR)
ORR was defined as the percentage of participants who had a confirmed complete response (CR) or confirmed partial response (PR) as their best overall response (BOR) recorded from the date of randomization until disease progression or initiation of new anti-cancer therapy, whichever is earlier based on blinded independent central review (BICR) evaluation criteria in solid tumors (RECIST) version 1.1 (v1.1). CR was defined as disappearance of all target lesions. Any pathological lymph nodes must be \<10 millimeter in the short axis. PR was defined as at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters (e.g., percent change from baseline).
Time frame: Up to approximately 20 months
Overall Survival (OS)
OS was defined as the time from the date of randomization to the date of death by any cause.
Time frame: Up to approximately 46 months
Progression-free Survival (PFS)
PFS was defined as the time from the date of randomization to the date of disease progression (PD) or death by any cause, whichever occurs first. PFS was evaluated using Response Evaluation Criteria in Solid Tumors Criteria (RECIST) version 1.1 based on Investigator assessment. PD is defined as at least a 20% increase in the sum of the diameters of target lesions, taking as a reference, the smallest sum of diameters recorded since the treatment started (e.g., percent change from nadir, where nadir is defined as the smallest sum of diameters recorded since treatment start).
Time frame: Up to approximately 46 months
Number of Participants With Treatment-emergent Adverse Event (TEAEs), TEAEs Leading to Death and TEAEs Leading to Treatment Discontinuation
AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study treatment, whether or not considered related to the study treatment. A TEAE is an event that emerges during treatment having been absent pretreatment or worsens relative to the pretreatment state. Number of participants with TEAEs, TEAEs leading to death, and TEAEs leading to treatment discontinuation are presented. AEs were coded using the Medical Dictionary for Regulatory Affairs (MedDRA dictionary).
Time frame: Up to 46 months
Number of Participants With Treatment Emergent Immune-related Adverse Event (irAE)
The irAEs are events which are severe or fatal and can occur in participants treated with monoclonal antibodies directed against immune checkpoints, including pembrolizumab and dostarlimab. While irAEs (eg, diarrhea/colitis, pneumonitis, nephritis, hypophysitis, adrenalitis, thyroiditis, severe skin reactions, uveitis, myocarditis, and hepatotoxicity) usually occur during treatment, symptoms can also manifest after discontinuation of treatment. AEs were coded using the MedDRA dictionary.
Time frame: Up to 46 months
Number of Participants With Serious AEs
An SAE is any untoward medical occurrence that, at any dose results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability or incapacity, is a congenital anomaly/birth defect or is an important medical event that may jeopardize the participant or may require medical or surgical intervention to prevent one of the above outcomes. SAEs are subset of AEs. AEs were coded using the MedDRA dictionary.
Time frame: Up to approximately 46 months
Number of Participants With Worst Case Clinical Chemistry Results Relative to Normal Range Post-Baseline Relative to Baseline
Normal ranges were 30 to 110 units per liter (U/L) (Amylase); 4. 5 to 5. 6 milligram/deciliters (mg/dL) (Calcium); 96 to 100 milliequivalents (mEq)/ L (Chloride); 2. 5 to 4.5 mg/dL (Phosphate); 6 to 8.3 grams/L (protein); 6 to 24 millimoles/L (Urea) and 7 to 20 mg/dL (Urea nitrogen). Participants were counted in worst case category that their value changes to low, normal or no change \[NC\] or high), unless there is NC in their category. Participants whose laboratory value category was unchanged (e.g. High to High) or whose value became normal, were recorded in "To Normal or No Change" category. Participants were counted twice if participant had values that changed To Low and To High, so percentages may not add to 100%.
Time frame: Up to approximately 46 months
Number of Participants With Worst Case Hematology Results Relative to Normal Range Post-Baseline Relative to Baseline
Normal ranges were 0.01 to 0.3\*10\^9 cells/L (basophils); 41 to 50 percentage of red blood cells (RBC) in blood (hematocrit); 80-100 femtoliters (fl) (erythrocytes \[referred as Ery\] mean corpuscular volume (EMCV)); 2 to 8 percentage of WBC (monocytes); and Women: 4.2 to 5.4 million RBC/ microliter (mcL) of blood and Men: 4.7 to 6.1 million RBC/ mcL (erythrocytes). Participants were counted in worst case category that their value changes to low, normal or no change \[NC\] or high), unless there is NC in their category. Participants whose laboratory value category was unchanged (e.g. High to High) or whose value became normal, were recorded in "To Normal or No Change" category. Participants were counted twice if participant had values that changed To Low and To High, so percentages may not add to 100%.
Time frame: Up to approximately 46 months
Number of Participants With Worst Case Urinalysis Results Post-Baseline Relative to Baseline
Urine samples were collected to assess urine Bilirubin, glucose, ketones, Leukocyte Esterase, Nitrite, occult blood and Protein using dipstick method. The dipstick test gave results in a semi-quantitative manner, and results for urinalysis parameters were recorded as No Change/Decreased, Increase to TRACE, Increase to +, Increase to ++, Increase to +++ and Increase to ++++. Baseline (Day 1) was defined as the most recent, non-missing value prior to or on the first study treatment dose date.
Time frame: Up to approximately 46 months
Change From Baseline (CFB) in Thyroid Functions: Free Triiodothyronine (T3) and Free Thyroxine (T4)
Blood samples were collected for the assessment Free Triiodothyronine (T3) and Free Thyroxine (T4).
Time frame: Up to approximately 46 months
Change From Baseline in Thyroid Function: Thyrotropin (TSH)
Blood samples were collected for the assessment of Thyroid Function Thyrotropin (TSH).
Time frame: Up to approximately 46 months
Change From Baseline in Thyroid Functions: Triiodothyronine (T3) and Thyroxine (T4)
Blood samples were collected for the assessment of Triiodothyronine (T3) and Thyroxine (T4).
Time frame: Up to approximately 46 months
Number of Participants With Worst-case Grade Change From Baseline in Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP)
DBP and SBP were measured in a semi-supine position after 5 minutes rest. Grades were derived based on numeric criteria as defined in Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0. Systolic Blood Pressure (SBP): Grade 0 (\<120 Millimetre of mercury (mmHg)), Grade 1 (120-139 mmHg), Grade 2 (140-159 mmHg), Grade 3 (\>=160 mmHg). Diastolic Blood Pressure (DBP): Grade 0 (\<80 mmHg), Grade 1 (80-89 mmHg), Grade 2 (90-99 mmHg), Grade 3 (\>=100 mmHg). An increase is defined as an increase in the CTCAE grade relative to the Baseline grade. Only those participants with grade increase have been presented. Participants with missing Baseline values were assumed to have a Baseline value of G0.
Time frame: Up to approximately 46 months
Number of Participants With Worst Case Pulse Rate Results Post-Baseline Relative to Baseline Based on Potential Clinical Importance (PCI)
Normal range of Pulse Rate was 60 to 100 beats/min. Participants were counted in worst case category that their value changes to low, to within \[w/in\] Range or No Change \[NC\] or high, unless there is NC in their category. Participants whose laboratory value category was unchanged (e.g. High to High) or whose value became normal, were recorded in "To Normal or No Change" category.
Time frame: Up to approximately 46 months
Number of Participants With Worst-Case Post-Baseline Eastern Cooperative Oncology Group (ECOG) Performance Status
Performance status was assessed using the ECOG scale (Grade 0-5). Grades: 0: Fully active, able to carry on all pre-disease performance without restriction. 1: Restricted in physically strenuous activity but ambulatory, able to carry out work of light nature. 2: Ambulatory, capable of self-care, unable to carry out work activities. Up and about more than 50% waking hours. 3: Capable of limited self-care, confined to bed/chair more than 50% waking hours. 4: Completely disabled. Cannot carry on any self-care. Totally confined to bed/chair. 5: Dead.
Time frame: Up to approximately 46 months
Mean Change From Baseline in Electrocardiogram (ECG) Parameters
Participants were in a supine or semi recumbent position (about 30 degrees of elevation) and rested for approximately 2 minutes before ECGs were recorded. Single 12-lead ECG was recorded using an ECG machine. PR, QRS, QT, QTcF, and RR intervals were recorded
Time frame: Baseline (Day 1), Cycle 1 Day 1, and end of treatment (Up to approximately 46 months)
Mean Change From Baseline in ECG Mean Heart Rate
Participants were in a supine or semi recumbent position (about 30 degrees of elevation) and rested for approximately 2 minutes before ECGs were recorded. Single 12-lead ECG was recorded using an ECG machine. Mean Heart rate were recorded.
Time frame: Baseline (Day 1), Cycle 1 Day 1, and end of treatment (Up to approximately 46 months)
Number Participant Who Used Concomitant Medications
Number of participants received concomitant medications were summarized.
Time frame: Up to approximately 46 months
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GSK Investigational Site
Córdoba, Argentina
GSK Investigational Site
Florida, Argentina
GSK Investigational Site
La Plata, Argentina
GSK Investigational Site
La Rioja, Argentina
GSK Investigational Site
Pergamino, Argentina
...and 48 more locations