A Platform Study of Novel Immunotherapy Combinations in Participants With Previously Untreated, Advanced/Metastatic Non-Small-Cell Lung Cancer
- Conditions
- Lung Cancer, Non-Small Cell
- Interventions
- Registration Number
- NCT05565378
- Lead Sponsor
- GlaxoSmithKline
- Brief Summary
This study will evaluate the efficacy, safety, pharmacokinetics (PK), and pharmacodynamics (PDy) of novel immunotherapy combinations compared with immunotherapy monotherapy in participants with Programmed death ligand-1 (PD L-1) high (Tumor cells \[TC\]/ Tumor proportion score \[TPS\] \>= 50%), previously untreated, unresectable, locally advanced or metastatic non-small cell lung cancer (NSCLC). Drug name mentioned as Belrestotug, GSK4428859A, and EOS884448 are all interchangeable for the same compound. In the rest of the document, the drug will be referred to as Belrestotug.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 340
- 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 2 years prior to 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
- 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 targeted therapy is available.
- Has NSCLC with a tumor that harbors any of the following molecular alterations: EGFR and /or ALK translocations mutations that are sensitive to available targeted inhibitor therapy, Any other known genomic aberrations or oncogenic driver mutations for which a locally approved targeted therapy is available for first-line treatment of locally advanced or metastatic NSCLC.
- Had major surgery within 4 weeks or lung radiation of >30 Gy therapy within 6 months prior to the first dose of study intervention
- Received prior therapy with any immune checkpoint inhibitors
- Never smoked, defined as smoking <100 tobacco cigarettes in a lifetime
- Has an invasive malignancy or history of invasive malignancy other than the disease under study within the last 5 years (clinical exceptions apply as per protocol)
- Symptomatic, untreated, or actively progressing, brain metastases or any leptomeningeal disease (regardless of symptomatology, treatment status, or stability)
- Autoimmune disease or syndrome that required systemic treatment within the past 2 years
- Receiving systemic steroid therapy <= 3 days prior to first dose of study intervention or 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
- Current unstable liver or biliary disease
- Severe infection within 4 weeks prior to the first dose of study intervention
- Positive for tuberculosis, human immunodeficiency virus (HIV) infection, hepatitis B surface antigen, or hepatitis C
- Has advanced, symptomatic, or visceral spread and is considered to be at imminent risk of life-threatening complications (including, but not limited to, massive uncontrolled effusions [e.g., pleural, pericardial, peritoneal])
- Is currently participating in or has participated in a study of an investigational therapy within 4 weeks prior to the first dose of study intervention
- Has a history of allogeneic tissue/stem cell transplant or solid organ transplant
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Substudy 1B Dostarlimab Participants will be administered with dostarlimab in a fixed dose followed by belrestotug in a fixed dose (Dose B). Substudy 1B Belrestotug Participants will be administered with dostarlimab in a fixed dose followed by belrestotug in a fixed dose (Dose B). Pembrolizumab Monotherapy Pembrolizumab Participants will be administered with pembrolizumab as monotherapy in a fixed dose. Dostarlimab Monotherapy Dostarlimab Participants will be administered with dostarlimab as monotherapy in a fixed dose. Substudy 1A Dostarlimab Participants will be administered with dostarlimab in a fixed dose followed by belrestotug in a fixed dose (Dose A). Substudy 1A Belrestotug Participants will be administered with dostarlimab in a fixed dose followed by belrestotug in a fixed dose (Dose A). Substudy 1C Dostarlimab Participants will be administered with dostarlimab in a fixed dose followed by belrestotug in a fixed dose (Dose C). Substudy 1C Belrestotug Participants will be administered with dostarlimab in a fixed dose followed by belrestotug in a fixed dose (Dose C). Substudy 2A Dostarlimab Participants will be administered with dostarlimab, fixed dose belrestotug, and fixed dose nelistotug Substudy 2A Belrestotug Participants will be administered with dostarlimab, fixed dose belrestotug, and fixed dose nelistotug Substudy 2A Nelistotug Participants will be administered with dostarlimab, fixed dose belrestotug, and fixed dose nelistotug
- Primary Outcome Measures
Name Time Method Objective Response Rate (ORR) to evaluate the antitumor activity of novel immunotherapy combinations compared with pembrolizumab Up to 24 months ORR, defined as the percentage of participants with complete response (CR) or partial response (PR) per RECIST 1.1 by investigator assessment.
- Secondary Outcome Measures
Name Time Method ORR to assess the dose response relationship of novel immunotherapy combinations across a range of the novel components dose levels and fixed dostarlimab dose Up to 24 months ORR, defined as the percentage of participants with CR or PR per RECIST 1.1 by Investigator assessment.
Progression free survival (PFS) to assess the clinical activity of novel immunotherapy combinations compared with pembrolizumab Up to 5 years PFS is defined as the time taken from the date of randomization to the date of first documented progressive disease (PD) per RECIST 1.1 by investigator assessment or death due to any cause, whichever comes first.
Overall survival (OS) to assess the clinical activity of novel immunotherapy combinations compared with pembrolizumab Up to 5 years OS is defined as the time from the date of randomization to the date of death due to any cause.
Duration of response (DOR) to assess the clinical activity of novel immunotherapy combinations compared with pembrolizumab Up to 5 years DOR is defined as the time from the date of first documented objective response (CR or PR) to the date of first documented PD per RECIST 1.1 by investigator assessment or death due to any cause, whichever comes first.
Progression free survival (PFS) to evaluate the antitumor activity of novel immunotherapy combinations for assessment of contribution of components for the combination regimens Up to 5 years PFS is defined as the time taken from the date of randomization to the date of first documented progressive disease (PD) per RECIST 1.1 by investigator assessment or death due to any cause, whichever comes first.
Overall survival (OS) to evaluate the antitumor activity of novel immunotherapy combinations for assessment of contribution of components for the combination regimens Up to 5 years OS is defined as the time from the date of randomization to the date of death due to any cause.
Duration of response (DOR) to evaluate the antitumor activity of novel immunotherapy combinations for assessment of contribution of components for the combination regimens Up to 5 years DOR is defined as the time from the date of first documented objective response (CR or PR) to the date of first documented PD per RECIST 1.1 by investigator assessment or death due to any cause, whichever comes first.
ORR to evaluate the antitumor activity of novel immunotherapy combinations for assessment of contribution of components for the combination regimens Up to 24 months ORR, defined as the percentage of participants with CR or PR per RECIST 1.1 by Investigator assessment.
Number of participants with Treatment Emergent Adverse Events (TEAEs) and Adverse Events of Special Interest (AESIs) Up to 5 years A TEAE is any event that was not present prior to the initiation of study intervention administration, or any event already present that worsens in intensity or frequency following exposure to study intervention. AESI are any Adverse Event (AE) (serious or non-serious) that is of scientific and medical concern specific to the study treatment and include infusion related reaction and immune-related adverse event (irAEs) from the date of enrollment to 90 days after last dose of study treatment.
Number of participants with Serious Adverse Events (SAEs) Up to 5 years 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 disability/incapacity, is a congenital anomaly/birth defect or any other situation according to medical or scientific judgment assessed by the investigator based on Common Terminology Criteria for Adverse Events (CTCAE) v5.0 from the date of enrollment to 90 days after last dose of study treatment.
Number of participants with TEAEs or SAEs leading to dose modifications (including dose delay and study intervention discontinuation) Up to 5 years Number of participants with positive antidrug antibodies (ADA) against belrestotug Up to 24 months Serum samples will be collected for the analysis of the presence of ADAs using validated immunoassays.
Number of participants with positive ADA against dostarlimab Up to 24 months Serum samples will be collected for the analysis of the presence of ADAs using validated immunoassays.
Number of participants with positive ADA against Nelistotug Up to 24 months Serum samples will be collected for the analysis of the presence of ADAs using validated immunoassays.
Maximum Observed Serum Concentration (Cmax) for belrestotug Up to 24 months Blood samples were collected for PK analysis of belrestotug.
Cmax for dostarlimab Up to 24 months Blood samples were collected for PK analysis of dostarlimab.
Cmax for Nelistotug Up to 24 months Blood samples were collected for PK analysis of Nelistotug.
Minimum Observed Serum Concentration (Cmin) for belrestotug Up to 24 months Blood samples were collected for PK analysis of belrestotug.
Cmin for dostarlimab Up to 24 months Blood samples were collected for PK analysis of dostarlimab.
Cmin for Nelistotug Up to 24 months Blood samples were collected for PK analysis of Nelistotug.
Trial Locations
- Locations (1)
GSK Investigational Site
🇬🇧Wolverhampton, United Kingdom