A Platform Study of Novel Immunotherapy Combinations in Participants With Previously Untreated, Advanced/Metastatic Non-Small-Cell Lung Cancer

• ClinicalTrials.gov Identifier: NCT05565378
• Recruitment Status: Recruiting
• First Posted: October 4, 2022
• Last Update Posted: February 21, 2024
• Sponsor: GlaxoSmithKline
• Collaborator: iTeos Therapeutics
• Information provided by (Responsible Party): GlaxoSmithKline

Tracking Information

• First Submitted Date: September 30, 2022
• First Posted Date: October 4, 2022
• Last Update Posted Date: February 21, 2024
• Actual Study Start Date: October 14, 2022
• Estimated Primary Completion Date: January 17, 2025 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: September 4, 2023)

Objective Response Rate (ORR) [ Time Frame: 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.

Original Primary Outcome Measures (submitted: September 30, 2022)

Objective Response Rate (ORR) [ Time Frame: Up to 24 months ]

ORR, defined as the percentage of participants achieving complete response (CR) or partial response (PR) per RECIST 1.1 by investigator assessment.

Current Secondary Outcome Measures (submitted: September 4, 2023)

• ORR for comparison between experimental arms [ Time Frame: 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) [ Time Frame: Up to 24 months ]
  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) [ Time Frame: 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) [ Time Frame: 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.
• Number of participants with Treatment Emergent adverse events (TEAEs) and Adverse events of Special Interest (AESIs) [ Time Frame: 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 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) [ Time Frame: 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 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) [ Time Frame: Up to 5 years ]
• Number of participants with positive antidrug antibodies (ADA) against belrestotug [ Time Frame: 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 antidrug antibodies (ADA) against dostarlimab [ Time Frame: 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 antidrug antibodies (ADA) against GSK6097608 [ Time Frame: 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 [ Time Frame: Up to 24 months ]
  Blood samples were collected for PK analysis of belrestotug.
• Maximum Observed Serum Concentration (Cmax) for dostarlimab [ Time Frame: Up to 24 months ]
  Blood samples were collected for PK analysis of dostarlimab.
• Maximum Observed Serum Concentration (Cmax) for GSK6097608 [ Time Frame: Up to 24 months ]
  Blood samples were collected for PK analysis of GSK6097608.
• Minimum Observed Serum Concentration (Cmin) for belrestotug [ Time Frame: Up to 24 months ]
  Blood samples were collected for PK analysis of belrestotug.
• Minimum Observed Serum Concentration (Cmin) for dostarlimab [ Time Frame: Up to 24 months ]
  Blood samples were collected for PK analysis of dostarlimab.
• Minimum Observed Serum Concentration (Cmin) for GSK6097608 [ Time Frame: Up to 24 months ]
  Blood samples were collected for PK analysis of GSK6097608.

Original Secondary Outcome Measures (submitted: September 30, 2022)

• ORR for comparison between experimental arms [ Time Frame: Up to 24 months ]
  ORR, defined as the percentage of participants achieving CR or PR per RECIST 1.1 by Investigator assessment.
• Progression free survival (PFS) [ Time Frame: Up to 24 months ]
  PFS is defined as the time taken from the date of randomization to the date of first documented progressive disease (PD) or death due to any cause, whichever comes first as per RECIST 1.1 by Investigator assessment.
• Overall survival (OS) [ Time Frame: Up to 5 years ]
  OS is defined as the time from the date of randomization to the date of death due to any cause as per RECIST 1.1 by Investigator assessment.
• Duration of response (DOR) [ Time Frame: 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 or death due to any cause, whichever comes first, as per RECIST 1.1 by Investigator assessment.
• Number of participants with Treatment Emergent adverse events (TEAEs) and Adverse events of Special Interest (AESIs) [ Time Frame: 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 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) [ Time Frame: 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 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) [ Time Frame: Up to 5 years ]
• Number of participants with positive antidrug antibodies (ADA) against GSK4428859A (EOS884448) [ Time Frame: 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 antidrug antibodies (ADA) against dostarlimab [ Time Frame: 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 GSK4428859A (EOS884448) [ Time Frame: Up to 24 months ]
  Blood samples were collected for PK analysis of GSK4428859A (EOS884448).
• Maximum Observed Serum Concentration (Cmax) for dostarlimab [ Time Frame: Up to 24 months ]
  Blood samples were collected for PK analysis of dostarlimab.
• Minimum Observed Serum Concentration (Cmin) for GSK4428859A (EOS884448) [ Time Frame: Up to 24 months ]
  Blood samples were collected for PK analysis of GSK4428859A (EOS884448).
• Minimum Observed Serum Concentration (Cmin) for dostarlimab [ Time Frame: Up to 24 months ]
  Blood samples were collected for PK analysis of dostarlimab.

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: A Platform Study of Novel Immunotherapy Combinations in Participants With Previously Untreated, Advanced/Metastatic Non-Small-Cell Lung Cancer
• Official Title: A Phase 2, Randomized, Open-label, Platform Study Utilizing a Master Protocol to Evaluate Novel Immunotherapy Combinations in Participants With Previously Untreated, Locally Advanced/Metastatic, Programmed Death Ligand 1-Selected Non-Small-Cell Lung Cancer
• 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 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 Provided
• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Lung Cancer, Non-Small Cell

Intervention

• Drug: Pembrolizumab
  Pembrolizumab will be administered as an IV infusion.
• Drug: Dostarlimab
  Dostarlimab will be administered as an IV infusion.
• Drug: Belrestotug
  Belrestotug will be administered as an IV infusion.
  Other Names:

  • EOS884448
  • GSK4428859A
• Drug: GSK6097608
  GSK6097608 will be administered as an IV infusion.

Study Arms

• Active Comparator: Pembrolizumab Monotherapy
  Participants will be administered an intravenous (IV) infusion of pembrolizumab as monotherapy in a fixed dose.
  Intervention: Drug: Pembrolizumab
• Experimental: Dostarlimab Monotherapy
  Participants will be administered an IV infusion of dostarlimab as monotherapy in a fixed dose.
  Intervention: Drug: Dostarlimab
• Experimental: Substudy 1A
  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).
  Interventions:

  • Drug: Dostarlimab
  • Drug: Belrestotug
• Experimental: Substudy 1B
  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).
  Interventions:

  • Drug: Dostarlimab
  • Drug: Belrestotug
• Experimental: Substudy 1C
  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).
  Interventions:

  • Drug: Dostarlimab
  • Drug: Belrestotug
• Experimental: Substudy 2
  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.
  Interventions:

  • Drug: Dostarlimab
  • Drug: Belrestotug
  • Drug: GSK6097608

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: September 30, 2022): 300
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: January 14, 2028
• Estimated Primary Completion Date: January 17, 2025 (Final data collection date for primary outcome measure)

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 recent 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

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 of >30 grays (Gy) therapy within 6 months prior to 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
• 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 and/or leptomeningeal disease (regardless of symptomatology, treatment status, or stability)
• 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 ≤6 months prior to enrollment
• Current unstable liver or biliary disease
• Severe infection within 4 weeks prior to randomization
• Positive for tuberculosis, human immunodeficiency virus (HIV) infection, hepatitis B, 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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: US GSK Clinical Trials Call Center; 877-379-3718; GSKClinicalSupportHD@gsk.com

Contact: EU GSK Clinical Trials Call Center; +44 (0) 20 89904466; GSKClinicalSupportHD@gsk.com

• Listed Location Countries: Argentina, Belgium, Brazil, Finland, France, Germany, Greece, Hungary, Italy, Japan, Korea, Republic of, Mexico, Netherlands, Poland, Portugal, South Africa, Spain, Thailand, Turkey, United Arab Emirates, United Kingdom, United States

Administrative Information

• NCT Number: NCT05565378
• Other Study ID Numbers: 213824; 2021-005115-32 ( EudraCT Number ); GALAXIES LUNG-201 ( Other Identifier: Study Identifier )
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: No

IPD Sharing Statement

• Plan to Share IPD: Yes
• Plan Description: IPD for this study will be made available via the Clinical Study Data Request site.
• Supporting Materials: Study Protocol
• Supporting Materials: Statistical Analysis Plan (SAP)
• Supporting Materials: Informed Consent Form (ICF)
• Supporting Materials: Clinical Study Report (CSR)
• Time Frame: IPD will be made available within 6 months of publishing the results of the primary endpoints, a key secondary endpoints and safety data of the study.
• Access Criteria: Access is provided after a research proposal is submitted and has received approval from the Independent Review Panel and after a Data Sharing Agreement is in place. Access is provided for an initial period of 12 months but an extension can be granted, when justified, for up to another 12 months.

• Current Responsible Party: GlaxoSmithKline
• Original Responsible Party: Same as current
• Current Study Sponsor: GlaxoSmithKline
• Original Study Sponsor: Same as current
• Collaborators: iTeos Therapeutics

Investigators

• Study Director: GSK Clinical Trials; GlaxoSmithKline

• PRS Account: GlaxoSmithKline
• Verification Date: February 2024