Clinical trial NCT06472076: A Study of Belrestotug Plus Dostarlimab Compared With Placebo Plus Pembrolizumab in Previously Untreated Participants With Programmed Death Ligand 1 (PD-L1) High Non-small-cell Lung Cancer (NSCLC)
Official title: A Randomized, Multicenter, Double-blind, Phase 3 Study to Investigate the Safety and Efficacy of Belrestotug in Combination With Dostarlimab Compared With Placebo in Combination With Pembrolizumab in Participants With Previously Untreated, Unresectable, Locally Advanced or Metastatic PD-L1 Selected Non-small Cell Lung Cancer (GALAXIES Lung-301)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Lung Cancer, Non-Small Cell
Keywords: Belrestotug
GSK4428859A
EOS-448
Dostarlimab
Pembrolizumab
PD-L1 selected NSCLC
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
Collaborators: name: iTeos Therapeutics
First posted: 2024-06-24
Enrollment: 1000
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: The goal of this clinical trial is to evaluate the efficacy and safety profile of dostarlimab in combination with belrestotug when compared with pembrolizumab and placebo in participants with previously untreated, unresectable, locally advanced or metastatic PD-L1 high NSCLC. Researchers will compare belrestotug plus dostarlimab with pembrolizumab plus placebo to see if there is meaningful improvement in progression free survival (PFS) and overall survival (OS).


Eligibility criteria: Inclusion Criteria:

* Has a 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
* Has not received prior systemic therapy for their locally advanced or metastatic NSCLC.
* Provides a fresh tumor tissue sample obtained at the time of or after the initial diagnosis of locally advanced or metastatic NSCLC.
* Has a PD-L1-high (Tumor cells \[TC\] ≥50%) tumor
* Has measurable disease (at least 1 target lesion) based on RECIST 1.1
* Has an Eastern Cooperative Oncology Group (ECOG) Performance status (PS) score of 0 or 1.
* Has adequate organ function

Exclusion Criteria:

* Has NSCLC with a tumor that harbors any of the following molecular alterations:

  1. Epidermal growth factor receptor (EGFR) mutations that are sensitive to available targeted inhibitor therapy
  2. Anaplastic lymphoma kinase (ALK) translocations that are sensitive to available targeted inhibitor therapy
  3. 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.
* Has had surgery within 4 weeks of the first dose of study intervention and has not recovered from AEs (i.e., has any ongoing surgery-related events ≥ Grade 1)/complications related to surgery or has received lung radiation therapy of \>30 gray (Gy) within 6 months
* Has received prior therapy with any immune checkpoint inhibitors, including antibodies or drugs targeting PD-(L)1, Cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), T cell immunoglobulin and ITIM domain (TIGIT), or other checkpoint pathways.
* Has 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, with the exception of those with a negligible risk of metastasis or death and/or treated with expected curative outcome.
* Has symptomatic, untreated, or actively progressin g brain metastases or leptomeningeal disease
* Has autoimmune disease or syndrome (current or history thereof) that required systemic treatment within the past 2 years.
* Has received any live vaccine within 30 days prior to first dose of study intervention.
* Has any history of idiopathic pulmonary fibrosis, organizing pneumonia, drug induced pneumonitis, idiopathic pneumonitis, or evidence of active pneumonitis.
* Has symptomatic ascites, pleural effusion, or pericardial effusion.
* Has active inflammatory bowel disease
* Has a history of significant acute or chronic cardiac diagnosis requiring intervention/treatment in the last 6 months.
* Has severe infection or complication thereof 4 weeks prior to randomisation including active tuberculosis.
* Has a history of allogeneic tissue/stem cell transplant or solid organ transplant.

Primary outcomes:
measure: Progression-free Survival (PFS) per Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST v1.1) by Blinded independent central review (BICR)
timeFrame: Up to approximately 5 years
measure: Overall Survival (OS)
timeFrame: Up to approximately 5 years
Secondary outcomes:
measure: Objective Response Rate (ORR)
timeFrame: Up to approximately 5 years
measure: Molecular Response Rate (MRR)
timeFrame: Up to approximately 5 years
measure: PFS per RECIST 1.1 by investigator assessment
timeFrame: Up to approximately 5 years
measure: Duration of Response (DOR)
timeFrame: Up to approximately 5 years
measure: Time to first subsequent therapy (TFST)
timeFrame: Up to approximately 5 years
measure: Number of Participants with Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs) and Adverse Events of Special Interest (AESIs)
timeFrame: Up to approximately 5 years
measure: Number of Participants with TEAEs or SAEs leading to dose modifications or study intervention discontinuation
timeFrame: Up to approximately 5 years
measure: Time to Deterioration (TTD) of lung cancer symptoms
timeFrame: Up to approximately 5 years
measure: TTD in physical functioning
timeFrame: Up to approximately 5 years
measure: Number of participants with anti-drug antibodies (ADA) against Dostarlimab
timeFrame: Up to approximately 5 years
measure: Number of participants with ADA against Belrestotug
timeFrame: Up to approximately 5 years
Other outcomes:
Locations:
city: Ocala
country: United States
facility: GSK Investigational Site
state: Florida
city: Honolulu
country: United States
facility: GSK Investigational Site
state: Hawaii
city: Edgewood
country: United States
facility: GSK Investigational Site
state: Kentucky
city: Lexington
country: United States
facility: GSK Investigational Site
state: Kentucky
city: Lexington
country: United States
facility: GSK Investigational Site
state: Kentucky
city: Omaha
country: United States
facility: GSK Investigational Site
state: Nebraska
city: Chattanooga
country: United States
facility: GSK Investigational Site
state: Tennessee
city: Nashville
country: United States
facility: GSK Investigational Site
state: Tennessee
city: Fort Worth
country: United States
facility: GSK Investigational Site
state: Texas
city: Fredericksburg
country: United States
facility: GSK Investigational Site
state: Virginia
city: Olympia
country: United States
facility: GSK Investigational Site
state: Washington
city: Cipoletti Rio Negro
country: Argentina
facility: GSK Investigational Site
city: Ciudad Autonoma de Buenos Aires
country: Argentina
facility: GSK Investigational Site
city: Ciudad Autonoma de Buenos Aire
country: Argentina
facility: GSK Investigational Site
city: Ciudad Autonoma De Bueno
country: Argentina
facility: GSK Investigational Site
city: Cordoba
country: Argentina
facility: GSK Investigational Site
city: Florida
country: Argentina
facility: GSK Investigational Site
city: Mendoza
country: Argentina
facility: GSK Investigational Site
city: Rosario
country: Argentina
facility: GSK Investigational Site
city: Rosario
country: Argentina
facility: GSK Investigational Site
city: San Miguel de TucumAn
country: Argentina
facility: GSK Investigational Site
city: Gent
country: Belgium
facility: GSK Investigational Site
city: Hasselt
country: Belgium
facility: GSK Investigational Site
city: Mont Gaston
country: Belgium
facility: GSK Investigational Site
city: Barretos
country: Brazil
facility: GSK Investigational Site
city: BelEm
country: Brazil
facility: GSK Investigational Site
city: CuritibaPR
country: Brazil
facility: GSK Investigational Site
city: Florianopolis
country: Brazil
facility: GSK Investigational Site
city: Fortaleza
country: Brazil
facility: GSK Investigational Site
city: Londrina
country: Brazil
facility: GSK Investigational Site
city: Porto VelhoRondOnia
country: Brazil
facility: GSK Investigational Site
city: Salvador
country: Brazil
facility: GSK Investigational Site
city: SAo JosE Do Rio PretoSP
country: Brazil
facility: GSK Investigational Site
city: Sao Paulo
country: Brazil
facility: GSK Investigational Site
city: VitOria
country: Brazil
facility: GSK Investigational Site
city: Haskovo
country: Bulgaria
facility: GSK Investigational Site
city: Plovdiv
country: Bulgaria
facility: GSK Investigational Site
city: Plovdiv
country: Bulgaria
facility: GSK Investigational Site
city: Edmonton
country: Canada
facility: GSK Investigational Site
state: Alberta
city: Halifax
country: Canada
facility: GSK Investigational Site
state: Nova Scotia
city: Chongqing
country: China
facility: GSK Investigational Site
state: Chongqing
city: Chengdu
country: China
facility: GSK Investigational Site
city: Hangzhou
country: China
facility: GSK Investigational Site
city: Hangzhou
country: China
facility: GSK Investigational Site
city: Hefei
country: China
facility: GSK Investigational Site
city: Nanjing
country: China
facility: GSK Investigational Site
city: Nanning
country: China
facility: GSK Investigational Site
city: Nantong
country: China
facility: GSK Investigational Site
city: Shanghai
country: China
facility: GSK Investigational Site
city: Suzhou
country: China
facility: GSK Investigational Site
city: Taizhou
country: China
facility: GSK Investigational Site
city: Wei Fang
country: China
facility: GSK Investigational Site
city: Wuhan
country: China
facility: GSK Investigational Site
city: Helsinki
country: Finland
facility: GSK Investigational Site
city: Kuopio
country: Finland
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: Angers cedex 9
country: France
facility: GSK Investigational Site
city: Boulogne Billancourt
country: France
facility: GSK Investigational Site
city: Limoges Cedex
country: France
facility: GSK Investigational Site
city: Lorient
country: France
facility: GSK Investigational Site
city: Pessac cedex
country: France
facility: GSK Investigational Site
city: Rennes
country: France
facility: GSK Investigational Site
city: Esslingen
country: Germany
facility: GSK Investigational Site
city: Frankfurt
country: Germany
facility: GSK Investigational Site
city: Gauting
country: Germany
facility: GSK Investigational Site
city: Halle
country: Germany
facility: GSK Investigational Site
city: Hamburg
country: Germany
facility: GSK Investigational Site
city: Shatin
country: Hong Kong
facility: GSK Investigational Site
city: GyOngyOs
country: Hungary
facility: GSK Investigational Site
city: VeszprEm
country: Hungary
facility: GSK Investigational Site
city: Gokul Shirgoan
country: India
facility: GSK Investigational Site
state: Kolhapur
city: Ahmedabad-380016
country: India
facility: GSK Investigational Site
city: Apex Wellness Hospital
country: India
facility: GSK Investigational Site
city: Bangalore
country: India
facility: GSK Investigational Site
city: Bangalore
country: India
facility: GSK Investigational Site
city: Belagavi
country: India
facility: GSK Investigational Site
city: Bhubaneshwar
country: India
facility: GSK Investigational Site
city: Bhubaneswar
country: India
facility: GSK Investigational Site
city: Gurgaon
country: India
facility: GSK Investigational Site
city: Kolkata
country: India
facility: GSK Investigational Site
city: New Delhi
country: India
facility: GSK Investigational Site
city: Avellino
country: Italy
facility: GSK Investigational Site
city: Bari
country: Italy
facility: GSK Investigational Site
city: Meldola FC
country: Italy
facility: GSK Investigational Site
city: Milano
country: Italy
facility: GSK Investigational Site
city: Pesaro
country: Italy
facility: GSK Investigational Site
city: Verona
country: Italy
facility: GSK Investigational Site
city: Aichi
country: Japan
facility: GSK Investigational Site
city: Chiba
country: Japan
facility: GSK Investigational Site
city: Ehime
country: Japan
facility: GSK Investigational Site
city: Ehime
country: Japan
facility: GSK Investigational Site
city: Fukuoka
country: Japan
facility: GSK Investigational Site
city: Fukuoka
country: Japan
facility: GSK Investigational Site
city: Gifu
country: Japan
facility: GSK Investigational Site
city: Gunma
country: Japan
facility: GSK Investigational Site
city: Hiroshima
country: Japan
facility: GSK Investigational Site
city: Hokkaido
country: Japan
facility: GSK Investigational Site
city: Hyogo
country: Japan
facility: GSK Investigational Site
city: Hyogo
country: Japan
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city: Kanagawa
country: Japan
facility: GSK Investigational Site
city: Kyoto
country: Japan
facility: GSK Investigational Site
city: Mie
country: Japan
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city: Miyagi
country: Japan
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city: Miyagi
country: Japan
facility: GSK Investigational Site
city: Nagasaki
country: Japan
facility: GSK Investigational Site
city: Niigata
country: Japan
facility: GSK Investigational Site
city: Okayama
country: Japan
facility: GSK Investigational Site
city: Osaka
country: Japan
facility: GSK Investigational Site
city: Osaka
country: Japan
facility: GSK Investigational Site
city: Tochigi
country: Japan
facility: GSK Investigational Site
city: Tokyo
country: Japan
facility: GSK Investigational Site
city: Tokyo
country: Japan
facility: GSK Investigational Site
city: Tokyo
country: Japan
facility: GSK Investigational Site
city: Tottori
country: Japan
facility: GSK Investigational Site
city: Wakayama
country: Japan
facility: GSK Investigational Site
city: Daegu
country: Korea, Republic of
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: Seoul
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: Guadajalara
country: Mexico
facility: GSK Investigational Site
city: La Paz BCS
country: Mexico
facility: GSK Investigational Site
city: Mexico City
country: Mexico
facility: GSK Investigational Site
city: San Luis PotosI
country: Mexico
facility: GSK Investigational Site
city: Tamaulipas
country: Mexico
facility: GSK Investigational Site
city: Alkmaar
country: Netherlands
facility: GSK Investigational Site
city: Den Haag
country: Netherlands
facility: GSK Investigational Site
city: Enschede
country: Netherlands
facility: GSK Investigational Site
city: Rotterdam
country: Netherlands
facility: GSK Investigational Site
city: Panama
country: Panama
facility: GSK Investigational Site
city: Punta Pacifica Panama City Panama
country: Panama
facility: GSK Investigational Site
city: Iloilo City
country: Philippines
facility: GSK Investigational Site
city: Manila
country: Philippines
facility: GSK Investigational Site
city: Bialystok
country: Poland
facility: GSK Investigational Site
city: Katowice
country: Poland
facility: GSK Investigational Site
city: Poznan
country: Poland
facility: GSK Investigational Site
city: Przemysl
country: Poland
facility: GSK Investigational Site
city: Rzeszow
country: Poland
facility: GSK Investigational Site
city: Alcabideche
country: Portugal
facility: GSK Investigational Site
city: Lisboa
country: Portugal
facility: GSK Investigational Site
city: Matosinhos
country: Portugal
facility: GSK Investigational Site
city: Singapore
country: Singapore
facility: GSK Investigational Site
city: A CoruNa
country: Spain
facility: GSK Investigational Site
city: Aravaca
country: Spain
facility: GSK Investigational Site
city: BaracaldoVizcaya
country: Spain
facility: GSK Investigational Site
city: Barcelona
country: Spain
facility: GSK Investigational Site
city: Barcelona
country: Spain
facility: GSK Investigational Site
city: Barcelona
country: Spain
facility: GSK Investigational Site
city: Barcelona
country: Spain
facility: GSK Investigational Site
city: Barcelona
country: Spain
facility: GSK Investigational Site
city: Cartagena Murcia
country: Spain
facility: GSK Investigational Site
city: COrdoba
country: Spain
facility: GSK Investigational Site
city: Jaen
country: Spain
facility: GSK Investigational Site
city: Jerez de la Frontera
country: Spain
facility: GSK Investigational Site
city: La CoruNa
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: Madrid
country: Spain
facility: GSK Investigational Site
city: MAlaga
country: Spain
facility: GSK Investigational Site
city: Oviedo
country: Spain
facility: GSK Investigational Site
city: Pamplona
country: Spain
facility: GSK Investigational Site
city: Salamanca
country: Spain
facility: GSK Investigational Site
city: Santander
country: Spain
facility: GSK Investigational Site
city: Sevilla
country: Spain
facility: GSK Investigational Site
city: Valladolid
country: Spain
facility: GSK Investigational Site
city: Gavle
country: Sweden
facility: GSK Investigational Site
city: Stockholm
country: Sweden
facility: GSK Investigational Site
city: Kaohsiung
country: Taiwan
facility: GSK Investigational Site
city: Kaohsiung
country: Taiwan
facility: GSK Investigational Site
city: Taipei
country: Taiwan
facility: GSK Investigational Site
city: Taipei
country: Taiwan
facility: GSK Investigational Site
city: Taipei
country: Taiwan
facility: GSK Investigational Site
city: Taoyuan
country: Taiwan
facility: GSK Investigational Site
city: Chiang Mai
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: Adana
country: Turkey
facility: GSK Investigational Site
city: Ankara
country: Turkey
facility: GSK Investigational Site
city: Ankara
country: Turkey
facility: GSK Investigational Site
city: Istanbul
country: Turkey
facility: GSK Investigational Site
Study officials:
References: