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)

NCT06472076 | Active Not Recruiting Phase 3 DMC FDA Drug

• 1 other identifier: 213823
• Study Type: interventional
• Target: 88
• Locations: 21 countries
• Sites: 134

Brief Summary

The goal of this clinical trial is to evaluate the safety and tolerability 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.

Conditions

Lung Cancer, Non-Small Cell

Keywords

Belrestotug; GSK4428859A; EOS-448; Dostarlimab; Pembrolizumab; PD-L1 selected NSCLC

Outcome Measures

Primary Outcomes (2)

• Number of Participants with Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)

  Up to approximately 138 weeks

• Number of Participants with TEAEs or SAEs leading to dose withdrawals or treatment discontinuation

  Up to approximately 138 weeks

Study Arms (2)

Dostarlimab plus belrestotug

EXPERIMENTAL

Biological: Dostarlimab; Biological: Belrestotug

Pembrolizumab plus placebo

ACTIVE COMPARATOR

Biological: Pembrolizumab; Drug: Placebo

Interventions

Dostarlimab BIOLOGICAL

Dostarlimab will be administered.

Dostarlimab plus belrestotug

Belrestotug BIOLOGICAL

Belrestotug will be administered.

Dostarlimab plus belrestotug

Pembrolizumab BIOLOGICAL

Pembrolizumab will be administered.

Pembrolizumab plus placebo

Placebo DRUG

Placebo will be administered.

Pembrolizumab plus placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• Has NSCLC with a tumor that harbors any of the following molecular alterations:
• Epidermal growth factor receptor (EGFR) mutations that are sensitive to available targeted inhibitor therapy
• Anaplastic lymphoma kinase (ALK) translocations 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.
• 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.

Sponsors & Collaborators

• GlaxoSmithKline: lead
• iTeos Therapeutics: collaborator

Study Sites (134)

GSK Investigational Site

Ocala, Florida, 34474, United States

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GSK Investigational Site

Honolulu, Hawaii, 96819, United States

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GSK Investigational Site

Lexington, Kentucky, 40503, United States

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Lexington, Kentucky, 40509, United States

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Ann Arbor, Michigan, 48106, United States

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Omaha, Nebraska, 68114, United States

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Nashville, Tennessee, 37203, United States

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Fort Worth, Texas, 76104, United States

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GSK Investigational Site

Olympia, Washington, 98506, United States

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GSK Investigational Site

Buenos Aires, 1425, Argentina

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Cipoletti Rio Negro, R8324CVE, Argentina

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Ciudad Autonoma de Buenos Aire, C1426AGE, Argentina

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Ciudad Autonoma de Bueno, C1056ABI, Argentina

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Córdoba, 5000, Argentina

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Florida, 1602, Argentina

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Mendoza, M5500AYB, Argentina

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Rosario, S2002KDT, Argentina

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Rosario, S2002, Argentina

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GSK Investigational Site

San Miguel de Tucumán, T4000, Argentina

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GSK Investigational Site

Hasselt, 3500, Belgium

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Mont Gaston, 5530, Belgium

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Barretos, 14784-400, Brazil

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Belém, 66.073-005, Brazil

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CuritibaPR, 80810-050, Brazil

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Florianópolis, 88034-000, Brazil

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Fortaleza, 60336-232, Brazil

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Londrina, 86015-520, Brazil

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Porto VelhoRondOnia, 76.834-899, Brazil

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Salvador, 40414-120, Brazil

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SAo JosE Do Rio PretoSP, 15090-000, Brazil

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São Paulo, 04312903, Brazil

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Vitória, 29043-260, Brazil

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Haskovo, 6300, Bulgaria

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Plovdiv, 4004, Bulgaria

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Halifax, Nova Scotia, B3H 1V7, Canada

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Chengdu, 610000, China

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Hangzhou, 310006, China

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Hangzhou, China

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Hefei, 230001, China

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Nanjing, 210006, China

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Shanghai, 200030, China

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Kuopio, 70210, Finland

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Turku, 20520, Finland

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Angers, 49000, France

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Boulogne-Billancourt, 92100, France

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Limoges, 87042, France

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Lorient, 56100, France

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Pessac, 33064, France

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Rennes, 35033, France

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Hamburg, 20251, Germany

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GSK Investigational Site

Shatin, Hong Kong

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Gokul Shirgoan, Kolhapur, 416234, India

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GSK Investigational Site

Ahmedabad-380016, 380 016, India

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Apex Wellness Hospital, 422005, India

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Bangalore, 560066, India

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Bangalore, 560085, India

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Belagavi, 590010, India

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Bhubaneshwar, 751007, India

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GSK Investigational Site

Bhubaneswar, 751019, India

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GSK Investigational Site

Gūrgaon, 122001, India

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Kolkata, 700020, India

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New Delhi, 110075, India

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Aichi, 466-8560, Japan

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Chiba, 273-8588, Japan

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Ehime, 790-0024, Japan

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Ehime, 791-0280, Japan

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Fukuoka, 812-8582, Japan

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Fukuoka, 814-0180, Japan

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Gifu, 503-8502, Japan

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Gunma, 377-0280, Japan

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Hiroshima, 737-0023, Japan

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Hokkaido, 062-0931, Japan

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Hyōgo, 665-0827, Japan

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Hyōgo, 670-8520, Japan

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Kanagawa, 236-0051, Japan

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Kyoto, 612-8555, Japan

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Mie, 515-8544, Japan

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Miyagi, 981-0914, Japan

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Miyagi, 981-1293, Japan

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Nagasaki, 852-8501, Japan

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Niigata, 951-8566, Japan

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Okayama, 710-8602, Japan

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Osaka, 591-8555, Japan

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Osaka, 596-8501, Japan

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Tochigi, 329-0498, Japan

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Tokyo, 104-0045, Japan

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Tokyo, 113-8603, Japan

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Tokyo, 162-8655, Japan

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Tottori, 683-8504, Japan

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Wakayama, 641-8510, Japan

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GSK Investigational Site

Guadajalara, 44280, Mexico

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La Paz BCS, 23040, Mexico

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Mexico City, 06700, Mexico

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San Luis Potosí City, 78209, Mexico

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Alkmaar, 1815 JD, Netherlands

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Enschede, 7512 KZ, Netherlands

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Panama City, Panama

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Punta Pacifica Panama City Panama, Panama

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Daegu, 41404, South Korea

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Incheon, 21565, South Korea

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Seoul, 02841, South Korea

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Seoul, 03312, South Korea

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GSK Investigational Site

Seoul, 05505, South Korea

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GSK Investigational Site

Seoul, 08308, South Korea

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Seoul, 120-752, South Korea

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GSK Investigational Site

A Coruña, 15006, Spain

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GSK Investigational Site

Aravaca, 28013, Spain

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BaracaldoVizcaya, 48903, Spain

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Barcelona, 08003, Spain

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GSK Investigational Site

Barcelona, 08023, Spain

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Barcelona, 08025, Spain

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GSK Investigational Site

Barcelona, 08035, Spain

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Cartagena Murcia, 30202, Spain

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Córdoba, 14004, Spain

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Jaén, 23007, Spain

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Las Palmas de Gran Canar, 35016, Spain

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GSK Investigational Site

Madrid, 28007, Spain

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GSK Investigational Site

Madrid, 28010, Spain

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GSK Investigational Site

Madrid, 28033, Spain

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GSK Investigational Site

Madrid, 28222, Spain

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Málaga, 29016, Spain

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GSK Investigational Site

Oviedo, 33006, Spain

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Pamplona, 31008, Spain

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Salamanca, 37007, Spain

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Santander, 39008, Spain

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Seville, 41014, Spain

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Valladolid, 47003, Spain

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GSK Investigational Site

Gävle, SE-801 87, Sweden

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Kaohsiung City, 807, Taiwan

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GSK Investigational Site

Taipei, 23561, Taiwan

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GSK Investigational Site

Adana, 1120, Turkey (Türkiye)

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GSK Investigational Site

Ankara, 06560, Turkey (Türkiye)

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GSK Investigational Site

Ankara, 06800, Turkey (Türkiye)

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GSK Investigational Site

Istanbul, 34722, Turkey (Türkiye)

Location

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

dostarlimab; pembrolizumab

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 18, 2024
• First Posted: June 24, 2024
• Study Start: June 10, 2024
• Primary Completion (Estimated): February 2, 2027
• Study Completion (Estimated): February 2, 2027
• Last Updated: September 10, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• 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.
• 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.

Locations

CN (6); BU (2); FI (2); BR (11); ME (4); US (9); CA (1); HK (1); JP (28); PA (2); SE (1); ES (22); BE (2); DE (1); TW (2); KR (7); AR (10); NL (2); FR (6); TU (4); IN (11)