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.
Name: Dostarlimab
Name: Pembrolizumab
Name: Chemotherapy
Description: ORR will be evaluated by RECIST v1.1 based on blinded independent central review (BICR) and will be defined as the proportion of participants with a best overall response (BOR) of complete response (CR) or partial response (PR) in the analysis population.
Measure: Overall Response Rate (ORR) by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 (v1.1). Time: Up to 5 yearsDescription: OS is defined as the time from the date of randomization to the date of death by any cause.
Measure: Overall survival (OS) Time: Up to 5 yearsDescription: PFS will be evaluated using RECIST v1.1 based on Investigator assessment and is defined as the time from the date of randomization to the date of progressive disease (PD) or death by any cause, whichever occurs first.
Measure: Progression free survival (PFS) by RECIST v1.1 Time: Up to 5 yearsDescription: A TEAE is any event that was not present prior to the initiation of study treatment or any event already present that worsens in either intensity or frequency following exposure to study treatment.
Measure: Number of participants with treatment-emergent adverse events (TEAEs) Time: Up to 5 yearsDescription: 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
Measure: Number of participants with serious adverse events (SAEs) Time: Up to 5 yearsDescription: The irAEs are events which may be 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.
Measure: Number of participants with immune related adverse events (irAEs) Time: Up to 5 yearsDescription: Number of participants with TEAEs leading to death will be assessed.
Measure: Number of participants with TEAEs leading to death Time: Up to 5 yearsDescription: Number of participants with AELDs will be assessed.
Measure: Number of participants with adverse events leading to discontinuation (AELD) Time: Up to 5 yearsDescription: Blood and urine samples will be collected to evaluate hematology, clinical chemistry, thyroid function and urinalysis lab parameters.
Measure: Number of participants with clinically significant changes in hematology, clinical chemistry, thyroid function and urinalysis lab parameters. Time: Up to 5 yearsDescription: Number of participants with abnormal vital signs will be assessed.
Measure: Number of participants with abnormal vital signs Time: Up to 5 yearsDescription: Performance status will be assessed using the ECOG scale (Grade 0-4). Grade 0 indicates fully active, able to carry on all pre-disease performance without restriction and Grade 4 indicates completely disabled, cannot carry on any self-care and totally confined to bed or chair.
Measure: Number of participants with abnormal Eastern Cooperative Oncology Group (ECOG) performance status Time: Up to 5 yearsDescription: Participants will be supine or in a semi-recumbent position and rested for approximately 2 minutes before ECGs are recorded.
Measure: Number of participants with abnormal electrocardiogram (ECG) parameters Time: Up to 5 yearsDescription: Physical examination will include assessments of the cardiovascular, respiratory, gastrointestinal, and neurological systems. Height and weight will also be measured and recorded.
Measure: Number of participants with abnormal physical examination Time: Up to 5 yearsDescription: Concomitant medications will be recorded.
Measure: Number of participants receiving concomitant medications Time: Up to 5 yearsAllocation: Randomized
Parallel Assignment
There is one SNP
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. --- V600E ---