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

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

This study will monitor the safety of novel immunotherapy combinations 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.

Study Overview

• Status: Active, not recruiting
• Conditions: Lung Cancer, Non-Small Cell
• Intervention / Treatment: Drug: Pembrolizumab; Drug: Belrestotug; Drug: Dostarlimab; Drug: Nelistotug

• Study Type: Interventional
• Enrollment (Actual): 351
• Phase: Phase 2

Contacts and Locations

Study Locations

• Argentina
  • Buenos Aires, Argentina, C1426ABP
    • GSK Investigational Site
  • Cipoletti Rio Negro, Argentina, R8324CVE
    • GSK Investigational Site
  • Ciudad Autonoma de Buenos Aire, Argentina, C1426AGE
    • GSK Investigational Site
  • Ciudad Autonoma de Buenos Aire, Argentina, 1414
    • GSK Investigational Site
  • Florida, Argentina, 1602
    • GSK Investigational Site
  • Mar del Plata, Argentina, 7600
    • GSK Investigational Site
  • San Juan, Argentina, J5402DIL
    • GSK Investigational Site
  • Santa Fe, Argentina, 3000
    • GSK Investigational Site
• Belgium
  • Wilrijk, Belgium, 2650
    • GSK Investigational Site
• Brazil
  • Barretos, Brazil, 14784-400
    • GSK Investigational Site
  • Porto Alegre, Brazil, 90610-000
    • GSK Investigational Site
  • São Paulo, Brazil, 01246-000
    • GSK Investigational Site
  • Vitória, Brazil, 29043-260
    • GSK Investigational Site
• Finland
  • Oulu, Finland, 90220
    • GSK Investigational Site
  • Tampere, Finland, 33520
    • GSK Investigational Site
  • Turku, Finland, 20520
    • GSK Investigational Site
  • Vaasa, Finland, 65130
    • GSK Investigational Site
• France
  • Bordeaux, France, 33076
    • GSK Investigational Site
  • Caen, France, 14033
    • GSK Investigational Site
  • Marseille, France, 13009
    • GSK Investigational Site
  • Quimper, France, 29107
    • GSK Investigational Site
  • Strasbourg, France, 67091
    • GSK Investigational Site
• Germany
  • Berlin, Germany, 13125
    • GSK Investigational Site
  • Essen, Germany, 45147
    • GSK Investigational Site
  • Großhansdorf, Germany, 22927
    • GSK Investigational Site
  • Heidelberg, Germany, 69126
    • GSK Investigational Site
  • Jena, Germany, 07747
    • GSK Investigational Site
• Greece
  • Athens, Greece, 11528
    • GSK Investigational Site
  • Haidari - Athens, Greece, 12462
    • GSK Investigational Site
  • Larissa, Greece, 41110
    • GSK Investigational Site
  • PapagosAthens, Greece, 115 27
    • GSK Investigational Site
  • Pylaia Thessaloniki, Greece, 57001
    • GSK Investigational Site
  • Thessaloniki, Greece, 57010
    • GSK Investigational Site
  • Thessaloniki, Greece, 54645
    • GSK Investigational Site
• Hungary
  • Budapest, Hungary, H-1121
    • GSK Investigational Site
  • Gyöngyös, Hungary, 3200
    • GSK Investigational Site
  • Tatabánya, Hungary, 2800
    • GSK Investigational Site
• Italy
  • Avellino, Italy, 83100
    • GSK Investigational Site
  • Bergamo, Italy, 24125
    • GSK Investigational Site
  • Genova, Italy, 16132
    • GSK Investigational Site
  • Pisa, Italy, 57124
    • GSK Investigational Site
  • Verona, Italy, 37045
    • GSK Investigational Site
• Japan
  • Chiba, Japan, 277-8577
    • GSK Investigational Site
  • Fukuoka, Japan, 812-8582
    • GSK Investigational Site
  • Hyōgo, Japan, 673-8558
    • GSK Investigational Site
  • Kanagawa, Japan, 241-8515
    • GSK Investigational Site
  • Osaka, Japan, 590-0197
    • GSK Investigational Site
  • Saitama, Japan, 350-1298
    • GSK Investigational Site
• Mexico
  • Guadalajara, Mexico, 44280
    • GSK Investigational Site
  • San Luis Potosí City, Mexico, 78209
    • GSK Investigational Site
• Netherlands
  • Enschede, Netherlands, 7512 KZ
    • GSK Investigational Site
  • Groningen, Netherlands, 9728 NZ
    • GSK Investigational Site
  • Leeuwarden, Netherlands, 8934 AD
    • GSK Investigational Site
  • Utrecht, Netherlands, 3543 AZ
    • GSK Investigational Site
• Poland
  • Lublin, Poland, 20-954
    • GSK Investigational Site
  • Prabuty, Poland, 82-550
    • GSK Investigational Site
  • Siedlce, Poland, 08-110
    • GSK Investigational Site
• Portugal
  • Gaia, Portugal, 4434-502
    • GSK Investigational Site
  • Guimarães, Portugal, 4835-044
    • GSK Investigational Site
  • Lisbon, Portugal, 1500-650
    • GSK Investigational Site
  • Lisbon, Portugal, 1998-018
    • GSK Investigational Site
  • Porto, Portugal, 4200-072
    • GSK Investigational Site
• South Africa
  • Cape Town, South Africa, 7570
    • GSK Investigational Site
  • Parktown, South Africa, 2193
    • GSK Investigational Site
• South Korea
  • Incheon, South Korea, 21565
    • GSK Investigational Site
  • Seoul, South Korea, 03080
    • GSK Investigational Site
  • Seoul, South Korea, 03722
    • GSK Investigational Site
  • Suwon Gyeonggi-do, South Korea, 442-723
    • GSK Investigational Site
• Spain
  • Badajoz, Spain, 06080
    • GSK Investigational Site
  • Badalona, Spain, 08916
    • GSK Investigational Site
  • Barcelona, Spain, 08035
    • GSK Investigational Site
  • Barcelona, Spain, 08907
    • GSK Investigational Site
  • Las Palmas de Gran Canar, Spain, 35016
    • GSK Investigational Site
  • Madrid, Spain, 28041
    • GSK Investigational Site
  • Madrid, Spain, 28046
    • GSK Investigational Site
  • Madrid, Spain, 28027
    • GSK Investigational Site
  • Málaga, Spain, 29010
    • GSK Investigational Site
  • PamplonaNavarra, Spain, 28027
    • GSK Investigational Site
  • Valencia, Spain, 46026
    • GSK Investigational Site
  • Valencia, Spain, 46009
    • GSK Investigational Site
• Thailand
  • Bangkok, Thailand, 10210
    • GSK Investigational Site
  • Chiang Mai, Thailand, 50200
    • GSK Investigational Site
  • Kho Hong Hat Yai, Thailand, 90110
    • GSK Investigational Site
  • Khon Kaen, Thailand, 40002
    • GSK Investigational Site
  • Pathum Thani, Thailand, 12120
    • GSK Investigational Site
• Turkey (Türkiye)
  • Ankara, Turkey (Türkiye), 06800
    • GSK Investigational Site
  • Ankara, Turkey (Türkiye), 06680
    • GSK Investigational Site
  • Antalya, Turkey (Türkiye), 07070
    • GSK Investigational Site
  • Istanbul, Turkey (Türkiye), 34214
    • GSK Investigational Site
  • Atakum
    • Samsun, Atakum, Turkey (Türkiye), 55200
      • GSK Investigational Site
• United Arab Emirates
  • Abu Dhabi, United Arab Emirates
    • GSK Investigational Site
  • Abu Dhabi, United Arab Emirates, 51900
    • GSK Investigational Site
• United Kingdom
  • Middlesbrough, United Kingdom, TS4 3BW
    • GSK Investigational Site
  • Middlesex, United Kingdom, HA6 2RN
    • GSK Investigational Site
  • Wolverhampton, United Kingdom, WV10 0QP
    • GSK Investigational Site
• United States
  • Florida
    • Plantation, Florida, United States, 33322
      • GSK Investigational Site
  • New Mexico
    • Albuquerque, New Mexico, United States, 87131
      • GSK Investigational Site
  • Tennessee
    • Chattanooga, Tennessee, United States, 37404
      • GSK Investigational Site
  • West Virginia
    • Morgantown, West Virginia, United States, 26506
      • GSK Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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 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:

• 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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Pembrolizumab Monotherapy; Participants will be administered with pembrolizumab as monotherapy in a fixed dose.	Drug: Pembrolizumab; Pembrolizumab will be administered.
Experimental: Dostarlimab Monotherapy; Participants will be administered with dostarlimab as monotherapy in a fixed dose.	Drug: Dostarlimab; Dostarlimab will be administered; Other Names: GSK4057190
Experimental: Substudy 1A; Participants will be administered with dostarlimab in a fixed dose followed by belrestotug in a fixed dose (Dose A).	Drug: Belrestotug; Belrestotug will be administered.; Other Names: EOS884448; GSK4428859A; Drug: Dostarlimab; Dostarlimab will be administered; Other Names: GSK4057190
Experimental: Substudy 1B; Participants will be administered with dostarlimab in a fixed dose followed by belrestotug in a fixed dose (Dose B).	Drug: Belrestotug; Belrestotug will be administered.; Other Names: EOS884448; GSK4428859A; Drug: Dostarlimab; Dostarlimab will be administered; Other Names: GSK4057190
Experimental: Substudy 1C; Participants will be administered with dostarlimab in a fixed dose followed by belrestotug in a fixed dose (Dose C).	Drug: Belrestotug; Belrestotug will be administered.; Other Names: EOS884448; GSK4428859A; Drug: Dostarlimab; Dostarlimab will be administered; Other Names: GSK4057190
Experimental: Substudy 2A; Participants will be administered with dostarlimab, fixed dose belrestotug, and fixed dose nelistotug	Drug: Belrestotug; Belrestotug will be administered.; Other Names: EOS884448; GSK4428859A; Drug: Dostarlimab; Dostarlimab will be administered; Other Names: GSK4057190; Drug: Nelistotug; Nelistotug will be administered.; Other Names: GSK6097608

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Number of Participants with Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)	Up to 228 weeks
Number of Participants with TEAEs or SAEs leading to dose modifications or treatment discontinuation	Up to 228 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	Serum samples will be collected for the analysis of the presence of ADAs using validated immunoassays.	Up to 24 months
Maximum Observed Serum Concentration (Cmax) for belrestotug	Blood samples were collected for PK analysis of belrestotug.	Up to 24 months
Minimum Observed Serum Concentration (Cmin) for belrestotug	Blood samples were collected for PK analysis of belrestotug.	Up to 24 months
ORR to assess the dose response relationship of novel immunotherapy combinations across a range of the novel components dose levels and fixed dostarlimab dose	ORR, defined as the percentage of participants with CR or PR per RECIST 1.1 by Investigator assessment.	Up to 24 months
Progression free survival (PFS) to assess the clinical activity of novel immunotherapy combinations compared with pembrolizumab	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.	Up to 5 years
Overall survival (OS) to assess the clinical activity of novel immunotherapy combinations compared with pembrolizumab	OS is defined as the time from the date of randomization to the date of death due to any cause.	Up to 5 years
Duration of response (DOR) to assess the clinical activity of novel immunotherapy combinations compared with pembrolizumab	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.	Up to 5 years
Progression free survival (PFS) to evaluate the antitumor activity of novel immunotherapy combinations for assessment of contribution of components for the combination regimens	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.	Up to 5 years
Overall survival (OS) to evaluate the antitumor activity of novel immunotherapy combinations for assessment of contribution of components for the combination regimens	OS is defined as the time from the date of randomization to the date of death due to any cause.	Up to 5 years
Duration of response (DOR) to evaluate the antitumor activity of novel immunotherapy combinations for assessment of contribution of components for the combination regimens	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.	Up to 5 years
ORR to evaluate the antitumor activity of novel immunotherapy combinations for assessment of contribution of components for the combination regimens	ORR, defined as the percentage of participants with CR or PR per RECIST 1.1 by Investigator assessment.	Up to 24 months
Number of participants with Treatment Emergent Adverse Events (TEAEs) and Adverse Events of Special Interest (AESIs)	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.	Up to 5 years
Number of participants with Serious Adverse Events (SAEs)	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.	Up to 5 years
Number of participants with positive ADA against dostarlimab	Serum samples will be collected for the analysis of the presence of ADAs using validated immunoassays.	Up to 24 months
Number of participants with positive ADA against Nelistotug	Serum samples will be collected for the analysis of the presence of ADAs using validated immunoassays.	Up to 24 months
Cmax for dostarlimab	Blood samples were collected for PK analysis of dostarlimab.	Up to 24 months
Cmax for Nelistotug	Blood samples were collected for PK analysis of Nelistotug.	Up to 24 months
Cmin for dostarlimab	Blood samples were collected for PK analysis of dostarlimab.	Up to 24 months
Cmin for Nelistotug	Blood samples were collected for PK analysis of Nelistotug.	Up to 24 months

Collaborators and Investigators

• Sponsor: GlaxoSmithKline
• Collaborators: iTeos Therapeutics
• Investigators: Study Director: GSK Clinical Trials, GlaxoSmithKline

Study record dates

Study Major Dates

• Study Start (Actual): October 14, 2022
• Primary Completion (Estimated): February 26, 2027
• Study Completion (Estimated): February 26, 2027

Study Registration Dates

• First Submitted: September 30, 2022
• First Submitted That Met QC Criteria: September 30, 2022
• First Posted (Actual): October 4, 2022

Study Record Updates

• Last Update Posted (Estimated): January 8, 2026
• Last Update Submitted That Met QC Criteria: January 7, 2026
• Last Verified: January 1, 2026

More Information

Terms related to this study

• Keywords: Immunotherapy; Pembrolizumab; Non-small-cell lung cancer; Dostarlimab; GSK6097608; GSK4428859A; EOS884448; Programmed death ligand 1; Belrestotug; Nelistotug; Programmed death protein 1 Inhibitor
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Respiratory Tract Diseases; Lung Diseases; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Carcinoma, Non-Small-Cell Lung; Antineoplastic Agents, Immunological; Immune Checkpoint Inhibitors; Antineoplastic Agents; Molecular Mechanisms of Pharmacological Action; pembrolizumab; dostarlimab
• Other Study ID Numbers: 213824; 2021-005115-32 (EudraCT Number); GALAXIES LUNG-201 (Other Identifier: Study Identifier)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Qualified researchers may request access to anonymized individual patient-level data (IPD) and related study documents of the eligible studies via the Data Sharing Portal. Details on GSK's data sharing criteria can be found at: https://www.gsk.com/en-gb/innovation/trials/data-transparency/
• IPD Sharing Time Frame: Anonymized IPD will be made available within 6 months of publication of primary, key secondary and safety results for studies in product with approved indication(s) or terminated asset(s) across all indications.
• IPD Sharing Access Criteria: Anonymized IPD is shared with researchers whose proposals are approved by an 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 may be granted, when justified, for up to 6 months.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; CSR

Drug and device information, study documents

• 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