A Platform Study of Novel Immunotherapy Combinations in Participants With Previously Untreated, Advanced/Metastatic Non-Small-Cell Lung Cancer
Lung Cancer, Non-Small Cell
About this trial
This is an interventional treatment trial for Lung Cancer, Non-Small Cell focused on measuring Non-small cell lung cancer, Dostarlimab, Pembrolizumab, PD-L1, GSK4428859A, EOS884448, PD-1 Inhibitor, Immunotherapy, Belrestotug, GSK6097608
Eligibility Criteria
Inclusion Criteria:
- Histologically or cytologically confirmed diagnosis of locally advanced unresectable NSCLC not eligible for curative surgery and/or definitive radiotherapy with or without chemotherapy or metastatic NSCLC (squamous or non squamous)
- No prior systemic therapy for their locally advanced or metastatic NSCLC
- Provides a fresh tumor tissue sample or archival sample collected within 6 months of screening
- PD-L1-high (TC/TPS ≥ 50%) tumor
- Measurable disease based on RECIST 1.1, as determined by the investigator
- Eastern Cooperative Oncology Group (ECOG) Performance Status score of 0 or 1
- Adequate baseline organ function
- Female participants of childbearing potential must use adequate contraception
Exclusion Criteria:
- Presence of Epidermal growth factor receptor (EGFR) mutations, Anaplastic lymphoma kinase (ALK) translocations, or other known genomic aberrations or oncogenic driver mutations for which a locally approved therapy is available. All participants with non squamous histology must have been tested for EGFR mutation and ALK translocation status.
- Had major surgery within 4 weeks or lung radiation therapy within 6 months of the first dose of study intervention
- Received prior therapy with any immune checkpoint inhibitors
- Never smoker, defined as smoking <100 tobacco cigarettes in a lifetime
- History of invasive malignancy other than the disease under study within the last 5 years
- Symptomatic, untreated, or actively progressing brain metastases and/or leptomeningeal disease
- Autoimmune disease or syndrome that required systemic treatment within the past 2 years
- Receiving any form of immunosuppressive medication
- Received any live vaccine ≤ 30 days prior to first dose of study intervention
- Any history of idiopathic pulmonary fibrosis, organizing pneumonia, drug induced pneumonitis, idiopathic pneumonitis, or evidence of active pneumonitis
- History or evidence of cardiac abnormalities ≤ 3 months prior to enrollment
- Current unstable liver or biliary disease
- Severe infection within 4 weeks prior to randomization
- Positive for tuberculosis, human immunodeficiency virus infection, hepatitis B, or hepatitis C
Sites / Locations
- GSK Investigational SiteRecruiting
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Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm 5
Arm 6
Active Comparator
Experimental
Experimental
Experimental
Experimental
Experimental
Pembrolizumab Monotherapy
Dostarlimab Monotherapy
Substudy 1A
Substudy 1B
Substudy 1C
Substudy 2
Participants will be administered an intravenous (IV) infusion of pembrolizumab as monotherapy in a fixed dose.
Participants will be administered an IV infusion of dostarlimab as monotherapy in a fixed dose.
Participants will be administered an IV infusion of dostarlimab in a fixed dose followed by an IV infusion of belrestotug in a fixed dose (Dose A).
Participants will be administered an IV infusion of dostarlimab in a fixed dose followed by an IV infusion of belrestotug in a fixed dose (Dose B).
Participants will be administered an IV infusion of dostarlimab in a fixed dose followed by an IV infusion of belrestotug in a fixed dose (Dose C).
Participants will be administered an IV infusion of dostarlimab in a fixed dose followed by an IV infusion of belrestotug along with IV infusion of GSK6097608 in a fixed dose.