Clinical trial NCT05565378: 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
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Lung Cancer, Non-Small Cell
Keywords: Belrestotug
Dostarlimab
EOS884448
GSK6097608
GSK4428859A
Nelistotug
Non-small-cell lung cancer
Pembrolizumab
Programmed death ligand 1
Programmed death protein 1 Inhibitor
Immunotherapy
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
Collaborators: name: iTeos Therapeutics
First posted: 2022-10-04
Enrollment: 351
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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 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 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

Primary outcomes:
measure: Objective Response Rate (ORR) to evaluate the antitumor activity of novel immunotherapy combinations compared with pembrolizumab
timeFrame: Up to 24 months
Secondary outcomes:
measure: ORR to assess the dose response relationship of novel immunotherapy combinations across a range of the novel components dose levels and fixed dostarlimab dose
timeFrame: Up to 24 months
measure: Progression free survival (PFS) to assess the clinical activity of novel immunotherapy combinations compared with pembrolizumab
timeFrame: Up to 5 years
measure: Overall survival (OS) to assess the clinical activity of novel immunotherapy combinations compared with pembrolizumab
timeFrame: Up to 5 years
measure: Duration of response (DOR) to assess the clinical activity of novel immunotherapy combinations compared with pembrolizumab
timeFrame: Up to 5 years
measure: Progression free survival (PFS) to evaluate the antitumor activity of novel immunotherapy combinations for assessment of contribution of components for the combination regimens
timeFrame: Up to 5 years
measure: Overall survival (OS) to evaluate the antitumor activity of novel immunotherapy combinations for assessment of contribution of components for the combination regimens
timeFrame: Up to 5 years
measure: Duration of response (DOR) to evaluate the antitumor activity of novel immunotherapy combinations for assessment of contribution of components for the combination regimens
timeFrame: Up to 5 years
measure: ORR to evaluate the antitumor activity of novel immunotherapy combinations for assessment of contribution of components for the combination regimens
timeFrame: Up to 24 months
measure: Number of participants with Treatment Emergent Adverse Events (TEAEs) and Adverse Events of Special Interest (AESIs)
timeFrame: Up to 5 years
measure: Number of participants with Serious Adverse Events (SAEs)
timeFrame: Up to 5 years
measure: Number of participants with TEAEs or SAEs leading to dose modifications (including dose delay and study intervention discontinuation)
timeFrame: Up to 5 years
measure: Number of participants with positive antidrug antibodies (ADA) against belrestotug
timeFrame: Up to 24 months
measure: Number of participants with positive ADA against dostarlimab
timeFrame: Up to 24 months
measure: Number of participants with positive ADA against Nelistotug
timeFrame: Up to 24 months
measure: Maximum Observed Serum Concentration (Cmax) for belrestotug
timeFrame: Up to 24 months
measure: Cmax for dostarlimab
timeFrame: Up to 24 months
measure: Cmax for Nelistotug
timeFrame: Up to 24 months
measure: Minimum Observed Serum Concentration (Cmin) for belrestotug
timeFrame: Up to 24 months
measure: Cmin for dostarlimab
timeFrame: Up to 24 months
measure: Cmin for Nelistotug
timeFrame: Up to 24 months
Other outcomes:
Locations:
city: Plantation
country: United States
facility: GSK Investigational Site
state: Florida
city: Albuquerque
country: United States
facility: GSK Investigational Site
state: New Mexico
city: Chattanooga
country: United States
facility: GSK Investigational Site
state: Tennessee
city: Morgantown
country: United States
facility: GSK Investigational Site
state: West Virginia
city: Buenos Aires
country: Argentina
facility: GSK Investigational Site
city: Cipoletti Rio Negro
country: Argentina
facility: GSK Investigational Site
city: Ciudad Autonoma de Buenos Aire
country: Argentina
facility: GSK Investigational Site
city: Ciudad Autonoma de Buenos Aire
country: Argentina
facility: GSK Investigational Site
city: Florida
country: Argentina
facility: GSK Investigational Site
city: Mar del Plata
country: Argentina
facility: GSK Investigational Site
city: San Juan
country: Argentina
facility: GSK Investigational Site
city: Santa Fe
country: Argentina
facility: GSK Investigational Site
city: Wilrijk
country: Belgium
facility: GSK Investigational Site
city: Barretos
country: Brazil
facility: GSK Investigational Site
city: Porto Alegre
country: Brazil
facility: GSK Investigational Site
city: Sao Paulo
country: Brazil
facility: GSK Investigational Site
city: VitOria
country: Brazil
facility: GSK Investigational Site
city: Oulu
country: Finland
facility: GSK Investigational Site
city: Tampere
country: Finland
facility: GSK Investigational Site
city: Turku
country: Finland
facility: GSK Investigational Site
city: Vaasa
country: Finland
facility: GSK Investigational Site
city: Bordeaux
country: France
facility: GSK Investigational Site
city: Caen Cedex 9
country: France
facility: GSK Investigational Site
city: Marseille
country: France
facility: GSK Investigational Site
city: Quimper cedex
country: France
facility: GSK Investigational Site
city: Strasbourg
country: France
facility: GSK Investigational Site
city: Berlin
country: Germany
facility: GSK Investigational Site
city: Essen
country: Germany
facility: GSK Investigational Site
city: Grosshansdorf
country: Germany
facility: GSK Investigational Site
city: Heidelberg
country: Germany
facility: GSK Investigational Site
city: Jena
country: Germany
facility: GSK Investigational Site
city: Athens
country: Greece
facility: GSK Investigational Site
city: Haidari - Athens
country: Greece
facility: GSK Investigational Site
city: Larissa
country: Greece
facility: GSK Investigational Site
city: PapagosAthens
country: Greece
facility: GSK Investigational Site
city: Pylaia Thessaloniki
country: Greece
facility: GSK Investigational Site
city: Thessaloniki
country: Greece
facility: GSK Investigational Site
city: Thessaloniki
country: Greece
facility: GSK Investigational Site
city: Budapest
country: Hungary
facility: GSK Investigational Site
city: GyOngyOs
country: Hungary
facility: GSK Investigational Site
city: TatabAnya
country: Hungary
facility: GSK Investigational Site
city: Avellino
country: Italy
facility: GSK Investigational Site
city: Bergamo
country: Italy
facility: GSK Investigational Site
city: Firenze
country: Italy
facility: GSK Investigational Site
city: Genova
country: Italy
facility: GSK Investigational Site
city: Pisa
country: Italy
facility: GSK Investigational Site
city: Verona
country: Italy
facility: GSK Investigational Site
city: Chiba
country: Japan
facility: GSK Investigational Site
city: Fukuoka
country: Japan
facility: GSK Investigational Site
city: Hyogo
country: Japan
facility: GSK Investigational Site
city: Kanagawa
country: Japan
facility: GSK Investigational Site
city: Osaka
country: Japan
facility: GSK Investigational Site
city: Saitama
country: Japan
facility: GSK Investigational Site
city: Incheon
country: Korea, Republic of
facility: GSK Investigational Site
city: Seoul
country: Korea, Republic of
facility: GSK Investigational Site
city: Seoul
country: Korea, Republic of
facility: GSK Investigational Site
city: Suwon Gyeonggi-do
country: Korea, Republic of
facility: GSK Investigational Site
city: Guadalajara
country: Mexico
facility: GSK Investigational Site
city: San Luis PotosI
country: Mexico
facility: GSK Investigational Site
city: Enschede
country: Netherlands
facility: GSK Investigational Site
city: Groningen
country: Netherlands
facility: GSK Investigational Site
city: Leeuwarden
country: Netherlands
facility: GSK Investigational Site
city: Utrecht
country: Netherlands
facility: GSK Investigational Site
city: Lublin
country: Poland
facility: GSK Investigational Site
city: Prabuty
country: Poland
facility: GSK Investigational Site
city: Siedlce
country: Poland
facility: GSK Investigational Site
city: Gaia
country: Portugal
facility: GSK Investigational Site
city: GuimarAes
country: Portugal
facility: GSK Investigational Site
city: Lisboa
country: Portugal
facility: GSK Investigational Site
city: Lisboa
country: Portugal
facility: GSK Investigational Site
city: Porto
country: Portugal
facility: GSK Investigational Site
city: Cape Town
country: South Africa
facility: GSK Investigational Site
city: Parktown
country: South Africa
facility: GSK Investigational Site
city: Badajoz
country: Spain
facility: GSK Investigational Site
city: Badalona
country: Spain
facility: GSK Investigational Site
city: Barcelona
country: Spain
facility: GSK Investigational Site
city: Barcelona
country: Spain
facility: GSK Investigational Site
city: Las Palmas De Gran Canar
country: Spain
facility: GSK Investigational Site
city: Madrid
country: Spain
facility: GSK Investigational Site
city: Madrid
country: Spain
facility: GSK Investigational Site
city: Madrid
country: Spain
facility: GSK Investigational Site
city: Malaga
country: Spain
facility: GSK Investigational Site
city: PamplonaNavarra
country: Spain
facility: GSK Investigational Site
city: Pozuelo De AlarcOn Madr
country: Spain
facility: GSK Investigational Site
city: Valencia
country: Spain
facility: GSK Investigational Site
city: Valencia
country: Spain
facility: GSK Investigational Site
city: Bangkok
country: Thailand
facility: GSK Investigational Site
city: Chiangmai
country: Thailand
facility: GSK Investigational Site
city: Kho Hong Hat Yai
country: Thailand
facility: GSK Investigational Site
city: Khon Kaen
country: Thailand
facility: GSK Investigational Site
city: Pathumthani
country: Thailand
facility: GSK Investigational Site
city: Samsun
country: Turkey
facility: GSK Investigational Site
state: Atakum
city: Ankara
country: Turkey
facility: GSK Investigational Site
city: Ankara
country: Turkey
facility: GSK Investigational Site
city: Antalya
country: Turkey
facility: GSK Investigational Site
city: Istanbul
country: Turkey
facility: GSK Investigational Site
city: Abu Dhabi
country: United Arab Emirates
facility: GSK Investigational Site
city: Abu Dhabi
country: United Arab Emirates
facility: GSK Investigational Site
city: Middlesbrough
country: United Kingdom
facility: GSK Investigational Site
city: Middlesex
country: United Kingdom
facility: GSK Investigational Site
city: Wolverhampton
country: United Kingdom
facility: GSK Investigational Site
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References: