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

Lung Cancer, Non-Small Cell Clinical Trial

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05565378
• Other study ID #: 213824
• Secondary ID: 2021-005115-32GA
• Status: Recruiting
• Phase: Phase 2
• Start date: October 14, 2022
• Est. completion date: January 14, 2028

Study information

• Verified date: February 2024
• Source: GlaxoSmithKline
• Contact: US GSK Clinical Trials Call Center
• Phone: 877-379-3718
• Email: GSKClinicalSupportHD[@]gsk.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 300
• Est. completion date: January 14, 2028
• Est. primary completion date: January 17, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Carcinoma, Non-Small-Cell Lung
• Lung Cancer, Non-Small Cell
• Lung Neoplasms

Intervention

Drug:
• Pembrolizumab
Pembrolizumab will be administered as an IV infusion.
• Dostarlimab
Dostarlimab will be administered as an IV infusion.
• Belrestotug
Belrestotug will be administered as an IV infusion.
• GSK6097608
GSK6097608 will be administered as an IV infusion.

Locations

Country	Name	City	State
Argentina	GSK Investigational Site	Buenos Aires
Argentina	GSK Investigational Site	Cipoletti, Rio Negro	Río Negro
Argentina	GSK Investigational Site	Ciudad Autonoma Buenos Aires	Buenos Aires
Argentina	GSK Investigational Site	Ciudad Autonoma de Buenos Aires	Buenos Aires
Argentina	GSK Investigational Site	Ciudad Autonoma de Buenos Aires
Argentina	GSK Investigational Site	Ciudad Autónoma de Buenos Aires	Buenos Aires
Argentina	GSK Investigational Site	Florida	Buenos Aires
Argentina	GSK Investigational Site	Mar del Plata	Buenos Aires
Argentina	GSK Investigational Site	San Juan
Argentina	GSK Investigational Site	Santa Fe
Belgium	GSK Investigational Site	Edegem
Brazil	GSK Investigational Site	Barretos	São Paulo
Brazil	GSK Investigational Site	Bela Vista	São Paulo
Brazil	GSK Investigational Site	Porto Alegre	Rio Grande Do Sul
Brazil	GSK Investigational Site	São Paulo
Brazil	GSK Investigational Site	Vitória	Espírito Santo
Finland	GSK Investigational Site	Oulu
Finland	GSK Investigational Site	Tampere
Finland	GSK Investigational Site	Turku
Finland	GSK Investigational Site	Vaasa
France	GSK Investigational Site	Bordeaux Cedex
France	GSK Investigational Site	Caen Cedex 9
France	GSK Investigational Site	Marseille
France	GSK Investigational Site	Quimper cedex
France	GSK Investigational Site	Strasbourg Cedex
Germany	GSK Investigational Site	Berlin
Germany	GSK Investigational Site	Dresden	Sachsen
Germany	GSK Investigational Site	Essen	Nordrhein-Westfalen
Germany	GSK Investigational Site	Grosshansdorf	Schleswig-Holstein
Germany	GSK Investigational Site	Heidelberg	Baden-Wuerttemberg
Germany	GSK Investigational Site	Jena	Thueringen
Greece	GSK Investigational Site	Athens
Greece	GSK Investigational Site	Athens
Greece	GSK Investigational Site	Athens
Greece	GSK Investigational Site	Larisa
Greece	GSK Investigational Site	Thessaloniki
Greece	GSK Investigational Site	Thessaloniki
Greece	GSK Investigational Site	Thessaloniki
Greece	GSK Investigational Site	Thessaloniki
Hungary	GSK Investigational Site	Budapest
Hungary	GSK Investigational Site	Farkasgyepu
Hungary	GSK Investigational Site	Gyöngyös
Hungary	GSK Investigational Site	Tatabánya
Hungary	GSK Investigational Site	Törökbálint
Italy	GSK Investigational Site	Avellino	Campania
Italy	GSK Investigational Site	Bergamo
Italy	GSK Investigational Site	Firenze	Toscana
Italy	GSK Investigational Site	Genova	Liguria
Italy	GSK Investigational Site	Legnago (VR)	Veneto
Italy	GSK Investigational Site	Livorno	Toscana
Italy	GSK Investigational Site	Roma	Lazio
Japan	GSK Investigational Site	Chiba
Japan	GSK Investigational Site	Fukuoka
Japan	GSK Investigational Site	Hyogo
Japan	GSK Investigational Site	Kanagawa
Japan	GSK Investigational Site	Osaka
Japan	GSK Investigational Site	Saitama
Korea, Republic of	GSK Investigational Site	Incheon
Korea, Republic of	GSK Investigational Site	Seoul
Korea, Republic of	GSK Investigational Site	Seoul
Korea, Republic of	GSK Investigational Site	Seoul
Korea, Republic of	GSK Investigational Site	Suwon, Gyeonggi-do
Mexico	GSK Investigational Site	Guadalajara	Jalisco
Mexico	GSK Investigational Site	San Luis Potosí
Mexico	GSK Investigational Site	Toluca de Lerdo	Estado De México
Netherlands	GSK Investigational Site	Enschede
Netherlands	GSK Investigational Site	Groningen
Netherlands	GSK Investigational Site	Leeuwarden
Netherlands	GSK Investigational Site	Utrecht
Poland	GSK Investigational Site	Lublin
Poland	GSK Investigational Site	Olsztyn
Poland	GSK Investigational Site	Prabuty
Poland	GSK Investigational Site	Siedlce
Poland	GSK Investigational Site	Wroclaw
Portugal	GSK Investigational Site	Guimarães
Portugal	GSK Investigational Site	Lisboa
Portugal	GSK Investigational Site	Lisboa
Portugal	GSK Investigational Site	Porto
Portugal	GSK Investigational Site	Vila Nova de Gaia
South Africa	GSK Investigational Site	Kraaifontein	Western Province
South Africa	GSK Investigational Site	Parktown	Gauteng
South Africa	GSK Investigational Site	Pretoria
Spain	GSK Investigational Site	Badajoz
Spain	GSK Investigational Site	Badalona
Spain	GSK Investigational Site	Barcelona
Spain	GSK Investigational Site	L'Hospitalet de Llobregat
Spain	GSK Investigational Site	Las Palmas De Gran Canaria
Spain	GSK Investigational Site	Madrid
Spain	GSK Investigational Site	Madrid
Spain	GSK Investigational Site	Madrid
Spain	GSK Investigational Site	Malaga
Spain	GSK Investigational Site	Pozuelo De Alarcón. Madrid.
Spain	GSK Investigational Site	Valencia
Spain	GSK Investigational Site	Valencia
Thailand	GSK Investigational Site	Bangkok
Thailand	GSK Investigational Site	Chiangmai
Thailand	GSK Investigational Site	Khlong Luang
Thailand	GSK Investigational Site	Khon Kaen
Thailand	GSK Investigational Site	Songkla
Turkey	GSK Investigational Site	Ankara
Turkey	GSK Investigational Site	Ankara
Turkey	GSK Investigational Site	Antalya
Turkey	GSK Investigational Site	Istanbul
United Arab Emirates	GSK Investigational Site	Abu Dhabi
United Arab Emirates	GSK Investigational Site	Abu-Dhabi
United Arab Emirates	GSK Investigational Site	Al-Ain
United Arab Emirates	GSK Investigational Site	Dubai
United Kingdom	GSK Investigational Site	Middlesbrough
United Kingdom	GSK Investigational Site	Northwood	Middlesex
United Kingdom	GSK Investigational Site	Wolverhampton	West Midlands
United States	GSK Investigational Site	Albuquerque	New Mexico
United States	GSK Investigational Site	Baltimore	Maryland
United States	GSK Investigational Site	Boston	Massachusetts
United States	GSK Investigational Site	Bryn Mawr	Pennsylvania
United States	GSK Investigational Site	Chattanooga	Tennessee
United States	GSK Investigational Site	Los Angeles	California
United States	GSK Investigational Site	Media	Pennsylvania
United States	GSK Investigational Site	Morgantown	West Virginia
United States	GSK Investigational Site	Paoli	Pennsylvania
United States	GSK Investigational Site	Plantation	Florida
United States	GSK Investigational Site	Wynnewood	Pennsylvania

Sponsors (2)

Lead Sponsor	Collaborator
GlaxoSmithKline	iTeos Therapeutics

Countries where clinical trial is conducted

United States,  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, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Objective Response Rate (ORR)	ORR, defined as the percentage of participants with complete response (CR) or partial response (PR) per RECIST 1.1 by investigator assessment.	Up to 24 months
Secondary	ORR for comparison between experimental arms	ORR, defined as the percentage of participants with CR or PR per RECIST 1.1 by Investigator assessment.	Up to 24 months
Secondary	Progression free survival (PFS)	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 24 months
Secondary	Overall survival (OS)	OS is defined as the time from the date of randomization to the date of death due to any cause.	Up to 5 years
Secondary	Duration of response (DOR)	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
Secondary	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 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
Secondary	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 CTCAE v5.0 from the date of enrollment to 90 days after last dose of study treatment.	Up to 5 years
Secondary	Number of participants with TEAEs or SAEs leading to dose modifications (including dose delay and study intervention discontinuation)		Up to 5 years
Secondary	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
Secondary	Number of participants with positive antidrug antibodies (ADA) against dostarlimab	Serum samples will be collected for the analysis of the presence of ADAs using validated immunoassays.	Up to 24 months
Secondary	Number of participants with positive antidrug antibodies (ADA) against GSK6097608	Serum samples will be collected for the analysis of the presence of ADAs using validated immunoassays.	Up to 24 months
Secondary	Maximum Observed Serum Concentration (Cmax) for belrestotug	Blood samples were collected for PK analysis of belrestotug.	Up to 24 months
Secondary	Maximum Observed Serum Concentration (Cmax) for dostarlimab	Blood samples were collected for PK analysis of dostarlimab.	Up to 24 months
Secondary	Maximum Observed Serum Concentration (Cmax) for GSK6097608	Blood samples were collected for PK analysis of GSK6097608.	Up to 24 months
Secondary	Minimum Observed Serum Concentration (Cmin) for belrestotug	Blood samples were collected for PK analysis of belrestotug.	Up to 24 months
Secondary	Minimum Observed Serum Concentration (Cmin) for dostarlimab	Blood samples were collected for PK analysis of dostarlimab.	Up to 24 months
Secondary	Minimum Observed Serum Concentration (Cmin) for GSK6097608	Blood samples were collected for PK analysis of GSK6097608.	Up to 24 months